# A global research priority agenda to advance public health responses to fatty liver disease

Jeffrey V Lazarus, Henry E Mark, Alina M Allen, Juan Pablo Arab, Patrizia Carrieri, Mazen Noureddin, William Alazawi, Naim Alkhouri, Saleh A Alqahtani, Marco Arrese, et al.

<figure><img src="image_1.png" /></figure>

## To cite this version:

Jeffrey V Lazarus, Henry E Mark, Alina M Allen, Juan Pablo Arab, Patrizia Carrieri, et al. A global research priority agenda to advance public health responses to fatty liver disease. Journal of Hepatology, 2023, 79, pp.618 - 634. 10.1016/j.jhep.2023.04.035. inserm-04546131

HAL Id: inserm-04546131

https://inserm.hal.science/inserm-04546131

Submitted on 15 Apr 2024

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_2.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
# A global research priority agenda to advance public health responses to fatty liver disease

Jeffrey V Lazarus, Henry E Mark, Alina M Allen, Juan Pablo Arab, Patrizia Carrieri, Mazen Noureddin, William Alazawi, Naim Alkhouri, Saleh A Alqahtani, Marco Arrese, et al.

► To cite this version:

Jeffrey V Lazarus, Henry E Mark, Alina M Allen, Juan Pablo Arab, Patrizia Carrieri, et al. A global research priority agenda to advance public health responses to fatty liver disease. Journal of Hepatology, 2023, 79, pp.618 - 634. 10.1016/j.jhep.2023.04.035. inserm-04546131

HAL Id: inserm-04546131

https://inserm.hal.science/inserm-04546131v1

Submitted on 15 Apr 2024

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_1.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
# A global research priority agenda to advance public health responses to fatty liver disease

## Authors

Jeffrey V. Lazarus, Henry E. Mark, Alina M. Allen, Juan Pablo Arab, Patrizia Carrieri, Mazen Noureddin, William Alazawi, Naim Alkhouri, Saleh A. Alqahtani, ..., Jörn M. Schattenberg, Vincent Wai-Sun Wong, Zobair M. Younossi

## Correspondence

Jeffrey.Lazarus@sph.cuny.edu (J.V. Lazarus).

## Graphical abstract

A research agenda for turning the tide on fatty liver disease

<figure><img src="image_3.png" /></figure>

An estimated 38% of adults and 13% of children and adolescents worldwide have fatty liver disease. Using a Delphi methodology, over two rounds a multidisciplinary panel (n = 288) from 94 countries reviewed and ranked fatty liver disease research priorities. Across rounds, consensus increased in all domains. The final research agenda comprises 28 priorities that can catalyse the global health community's efforts to advance and accelerate responses to this widespread and fast-growing public health threat.

## Highlights

* A large, global multidisciplinary panel reached high agreement levels on 28 fatty liver disease research priorities.

* Priorities spanned a broad range of areas, from disease burden and health system responses to policy and treatment.

* Consensus increased in all 6 research domains across two voting rounds, from 78.3 in R1 to 81.1 in R2.

* The mean level of combined agreement ('agree' + 'somewhat agree') across all priorities in R2 was 97.7%.

* All priorities had >90% combined agreement ('agree' + 'somewhat agree') and 5 of these achieved unanimous agreement.

## Impact and implications

An estimated 38% of adults and 13% of children and adolescents worldwide have fatty liver disease, making it the most prevalent liver disease in history. Despite substantial scientific progress in the past three decades, the burden continues to grow, with an urgent need to advance understanding of how to prevent, manage, and treat the disease. Through a global consensus process, a multidisciplinary group agreed on 28 research priorities covering a broad range of themes, from disease burden, treatment, and health system responses to awareness and policy. The findings have relevance for clinical and non-clinical researchers as well as funders working on fatty liver disease and non-communicable diseases more broadly, setting out a prioritised, ranked research agenda for turning the tide on this fast-growing public health threat.
# A global research priority agenda to advance public health responses to fatty liver disease

## Authors

Jeffrey V. Lazarus, Henry E. Mark, Alina M. Allen, Juan Pablo Arab, Patrizia Carrieri, Mazen Noureddin, William Alazawi, Naim Alkhouri, Saleh A. Alqahtani, ..., Jörn M. Schattenberg, Vincent Wai-Sun Wong, Zobair M. Younossi

## Correspondence

Jeffrey.Lazarus@sph.cuny.edu (J.V. Lazarus).

## Graphical abstract

A research agenda for turning the tide on fatty liver disease

<figure><img src="image_2.png" /></figure>

An estimated 38% of adults and 13% of children and adolescents worldwide have fatty liver disease. Using a Delphi methodology, over two rounds a multidisciplinary panel (n = 288) from 94 countries reviewed and ranked fatty liver disease research priorities. Across rounds, consensus increased in all domains. The final research agenda comprises 28 priorities that can catalyse the global health community's efforts to advance and accelerate responses to this widespread and fast-growing public health threat.

## Highlights

* A large, global multidisciplinary panel reached high agreement levels on 28 fatty liver disease research priorities.

* Priorities spanned a broad range of areas, from disease burden and health system responses to policy and treatment.

* Consensus increased in all 6 research domains across two voting rounds, from 78.3 in R1 to 81.1 in R2.

* The mean level of combined agreement ('agree' + 'somewhat agree') across all priorities in R2 was 97.7%.

* All priorities had >90% combined agreement ('agree' + 'somewhat agree') and 5 of these achieved unanimous agreement.

## Impact and implications

An estimated 38% of adults and 13% of children and adolescents worldwide have fatty liver disease, making it the most prevalent liver disease in history. Despite substantial scientific progress in the past three decades, the burden continues to grow, with an urgent need to advance understanding of how to prevent, manage, and treat the disease. Through a global consensus process, a multidisciplinary group agreed on 28 research priorities covering a broad range of themes, from disease burden, treatment, and health system responses to awareness and policy. The findings have relevance for clinical and non-clinical researchers as well as funders working on fatty liver disease and non-communicable diseases more broadly, setting out a prioritised, ranked research agenda for turning the tide on this fast-growing public health threat.
# A global research priority agenda to advance public health responses to fatty liver disease

Jeffrey V. Lazarus<sup>1,2,3,*†</sup>, Henry E. Mark<sup>4,5,†</sup>, Alina M. Allen<sup>6,†</sup>, Juan Pablo Arab<sup>7,8,9,†</sup>, Patrizia Carrieri<sup>10,†</sup>, Mazen Noureddin<sup>11,†</sup>, William Alazawi<sup>12</sup>, Naim Alkhouri<sup>13</sup>, Saleh A. Alqahtani<sup>14</sup>, Marco Arrese<sup>9</sup>, Ramon Bataller<sup>15</sup>, Thomas Berg<sup>16</sup>, Paul N. Brennan<sup>17</sup>, Patrizia Burra<sup>18</sup>, Graciela E. Castro-Narro<sup>19,20,21</sup>, Helena Cortez-Pinto<sup>22</sup>, Kenneth Cusi<sup>23</sup>, Nikos Dedes<sup>24</sup>, Ajay Duseja<sup>25</sup>, Sven M. Francque<sup>26,27</sup>, Hannes Hagström<sup>28</sup>, Terry T.-K. Huang<sup>3,29</sup>, Dana Ivancovsky Wajcman<sup>1</sup>, Achim Kautz<sup>30</sup>, Christopher J. Kopka<sup>31</sup>, Aleksander Krag<sup>32</sup>, Veronica Miller<sup>33</sup>, Philip N. Newsome<sup>34</sup>, Mary E. Rinella<sup>35</sup>, Diana Romero<sup>36</sup>, Shiv Kumar Sarin<sup>37</sup>, Marcelo Silva<sup>38</sup>, C. Wendy Spearman<sup>39</sup>, Emmanuel A. Tsochatzis<sup>40</sup>, Luca Valenti<sup>41,42</sup>, Marcela Villota-Rivas<sup>1</sup>, Shira Zelber-Sagi<sup>43,44</sup>, Jörn M. Schattenberg<sup>45,‡</sup>, Vincent Wai-Sun Wong<sup>46,‡</sup>, Zobair M. Younossi<sup>47,‡</sup>, on behalf of the Healthy Livers, Healthy Lives Collaborators

Journal of Hepatology **2023**. vol. 79 | 618–634

<figure><img src="image_4.png" /></figure>

Check for updates

**Background & aims:** An estimated 38% of adults worldwide have non-alcoholic fatty liver disease (NAFLD). From individual impacts to widespread public health and economic consequences, the implications of this disease are profound. This study aimed to develop an aligned, prioritised fatty liver disease research agenda for the global health community.

**Methods:** Nine co-chairs drafted initial research priorities, subsequently reviewed by 40 core authors and debated during a three-day in-person meeting. Following a Delphi methodology, over two rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the priorities, via Qualtrics XM, indicating agreement using a four-point Likert-scale and providing written feedback. The core group revised the draft priorities between rounds. In R2, panellists also ranked the priorities within six domains: epidemiology, models of care, treatment and care, education and awareness, patient and community perspectives, and leadership and public health policy.

**Results:** The consensus-built fatty liver disease research agenda encompasses 28 priorities. The mean percentage of 'agree' responses increased from 78.3 in R1 to 81.1 in R2. Five priorities received unanimous combined agreement ('agree' + 'somewhat agree'); the remaining 23 priorities had >90% combined agreement. While all but one of the priorities exhibited at least a super-majority of agreement (>66.7% 'agree'), 13 priorities had <80% 'agree', with greater reliance on 'somewhat agree' to achieve >90% combined agreement.

**Conclusions:** Adopting this multidisciplinary consensus-built research priorities agenda can deliver a step-change in addressing fatty liver disease, mitigating against its individual and societal harms and proactively altering its natural history through prevention, identification, treatment, and care. This agenda should catalyse the global health community's efforts to advance and accelerate responses to this widespread and fast-growing public health threat.

© 2023 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

## Introduction

Over the past three decades, the fatty liver disease burden has increased drastically. An estimated 38% (95% CI 33.71-42.49) of the global adult population<sup>1,2</sup> and around 13% of children and adolescents,<sup>3</sup> now have the disease. Left unmanaged, the disease can progress through increasing stages of hepatic fibrosis, leading to cirrhosis and associated complications, including hepatocellular carcinoma (HCC) (Box 1).<sup>4,5</sup> Fatty liver disease causes quality of life impairments, which worsen with disease progression and are compounded by comorbidities.<sup>6–8</sup> Fatty liver disease is a leading cause of HCC, which is the second leading cause of years of life lost amongst all cancers.<sup>9</sup> Beyond the human toll, the disease has wide-reaching social

and economic implications and yet it remains under-recognised and under-evaluated.<sup>10,11</sup>

Through cardiometabolic risk factors, fatty liver disease shares a complex bi-directional relationship with other common diseases, including cardiovascular disease, the leading cause of death in those with fatty liver disease.<sup>13</sup> Type 2 diabetes mellitus, cancer, sarcopenia, and chronic kidney disease are all commonly associated with fatty liver disease,<sup>14,15</sup> with the risk of extrahepatic complications increasing in parallel with liver disease severity.<sup>15</sup>

The multisystem nature of fatty liver disease has important implications for patient management, including the development of multi-disciplinary care models.<sup>16</sup> A lack of specific

Keywords: Delphi method; Global health; Non-communicable disease (NCD); NAFLD/NASH; Steatotic liver disease.

Received 5 April 2023; received in revised form 21 April 2023; accepted 26 April 2023; available online 20 June 2023

* Corresponding author. The City University of New York Graduate School of Public Health and Health Policy (CUNY SPH), New York, NY, USA.

E-mail address: Jeffrey.Lazarus@sph.cuny.edu (J.V. Lazarus).

† Contributed equally as first authors

‡ Contributed equally as senior authors

https://doi.org/10.1016/j.jhep.2023.04.035

<figure><img src="image_5.png" /></figure>
# A global research priority agenda to advance public health responses to fatty liver disease

Jeffrey V. Lazarus<sup>1,2,3,*†</sup>, Henry E. Mark<sup>4,5,†</sup>, Alina M. Allen<sup>6,†</sup>, Juan Pablo Arab<sup>7,8,9,†</sup>, Patrizia Carrieri<sup>10,†</sup>, Mazen Noureddin<sup>11,†</sup>, William Alazawi<sup>12</sup>, Naim Alkhouri<sup>13</sup>, Saleh A. Alqahtani<sup>14</sup>, Marco Arrese<sup>9</sup>, Ramon Bataller<sup>15</sup>, Thomas Berg<sup>16</sup>, Paul N. Brennan<sup>17</sup>, Patrizia Burra<sup>18</sup>, Graciela E. Castro-Narro<sup>19,20,21</sup>, Helena Cortez-Pinto<sup>22</sup>, Kenneth Cusi<sup>23</sup>, Nikos Dedes<sup>24</sup>, Ajay Duseja<sup>25</sup>, Sven M. Francque<sup>26,27</sup>, Hannes Hagström<sup>28</sup>, Terry T.-K. Huang<sup>3,29</sup>, Dana Ivancovsky Wajcman<sup>1</sup>, Achim Kautz<sup>30</sup>, Christopher J. Kopka<sup>31</sup>, Aleksander Krag<sup>32</sup>, Veronica Miller<sup>33</sup>, Philip N. Newsome<sup>34</sup>, Mary E. Rinella<sup>35</sup>, Diana Romero<sup>36</sup>, Shiv Kumar Sarin<sup>37</sup>, Marcelo Silva<sup>38</sup>, C. Wendy Spearman<sup>39</sup>, Emmanuel A. Tsochatzis<sup>40</sup>, Luca Valenti<sup>41,42</sup>, Marcela Villota-Rivas<sup>1</sup>, Shira Zelber-Sagi<sup>43,44</sup>, Jörn M. Schattenberg<sup>45,‡</sup>, Vincent Wai-Sun Wong<sup>46,‡</sup>, Zobair M. Younossi<sup>47,‡</sup>, on behalf of the Healthy Livers, Healthy Lives Collaborators

Journal of Hepatology **2023**. vol. 79 | 618–634

<figure><img src="image_3.png" /></figure>

Check for updates

**Background & aims:** An estimated 38% of adults worldwide have non-alcoholic fatty liver disease (NAFLD). From individual impacts to widespread public health and economic consequences, the implications of this disease are profound. This study aimed to develop an aligned, prioritised fatty liver disease research agenda for the global health community.

**Methods:** Nine co-chairs drafted initial research priorities, subsequently reviewed by 40 core authors and debated during a three-day in-person meeting. Following a Delphi methodology, over two rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the priorities, via Qualtrics XM, indicating agreement using a four-point Likert-scale and providing written feedback. The core group revised the draft priorities between rounds. In R2, panellists also ranked the priorities within six domains: epidemiology, models of care, treatment and care, education and awareness, patient and community perspectives, and leadership and public health policy.

**Results:** The consensus-built fatty liver disease research agenda encompasses 28 priorities. The mean percentage of ‘agree’ responses increased from 78.3 in R1 to 81.1 in R2. Five priorities received unanimous combined agreement (‘agree’ + ‘somewhat agree’); the remaining 23 priorities had >90% combined agreement. While all but one of the priorities exhibited at least a super-majority of agreement (>66.7% ‘agree’), 13 priorities had <80% ‘agree’, with greater reliance on ‘somewhat agree’ to achieve >90% combined agreement.

**Conclusions:** Adopting this multidisciplinary consensus-built research priorities agenda can deliver a step-change in addressing fatty liver disease, mitigating against its individual and societal harms and proactively altering its natural history through prevention, identification, treatment, and care. This agenda should catalyse the global health community’s efforts to advance and accelerate responses to this widespread and fast-growing public health threat.

© 2023 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver. This is an open access article under the CC BY-NC-ND license ([http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/)).

## Introduction

Over the past three decades, the fatty liver disease burden has increased drastically. An estimated 38% (95% CI 33.71-42.49) of the global adult population<sup>1,2</sup> and around 13% of children and adolescents,<sup>3</sup> now have the disease. Left unmanaged, the disease can progress through increasing stages of hepatic fibrosis, leading to cirrhosis and associated complications, including hepatocellular carcinoma (HCC) (Box 1).<sup>4,5</sup> Fatty liver disease causes quality of life impairments, which worsen with disease progression and are compounded by comorbidities.<sup>6–8</sup> Fatty liver disease is a leading cause of HCC, which is the second leading cause of years of life lost amongst all cancers.<sup>9</sup> Beyond the human toll, the disease has wide-reaching social

and economic implications and yet it remains under-recognised and under-evaluated.<sup>10,11</sup>

Through cardiometabolic risk factors, fatty liver disease shares a complex bi-directional relationship with other common diseases, including cardiovascular disease, the leading cause of death in those with fatty liver disease.<sup>13</sup> Type 2 diabetes mellitus, cancer, sarcopenia, and chronic kidney disease are all commonly associated with fatty liver disease,<sup>14,15</sup> with the risk of extrahepatic complications increasing in parallel with liver disease severity.<sup>15</sup>

The multisystem nature of fatty liver disease has important implications for patient management, including the development of multi-disciplinary care models.<sup>16</sup> A lack of specific

Keywords: Delphi method; Global health; Non-communicable disease (NCD); NAFLD/NASH; Steatotic liver disease.

Received 5 April 2023; received in revised form 21 April 2023; accepted 26 April 2023; available online 20 June 2023

* Corresponding author. The City University of New York Graduate School of Public Health and Health Policy (CUNY SPH), New York, NY, USA.

E-mail address: Jeffrey.Lazarus@sph.cuny.edu (J.V. Lazarus).

† Contributed equally as first authors

‡ Contributed equally as senior authors

https://doi.org/10.1016/j.jhep.2023.04.035

<figure><img src="image_4.png" /></figure>
symptoms often leads to a clinically relevant delay in diagnosis.¹⁷,¹⁸ Non-invasive tests (NITs) provide a practical and safe way of assessing fibrosis severity¹⁹ and the risk of future liver-related events.²⁰,²¹ NITs have been used in the development of pathways to identify and stratify patients based on care needs,²²⁻²⁵ yet such pathways are not implemented in the majority of healthcare settings.¹⁶

Several pharmacological treatments are under development, with some in late-stage clinical trials.²⁶,²⁷ However, India is the only country where regulators have approved a pharmacological treatment for routine use in fatty liver disease (saroglitazar).²⁸ In the absence of pharmacological treatments approved for NASH, management is focused on improving insulin resistance and weight loss, when needed, and on attenuating the pro-inflammatory milieu of obesity, which are the predominant disease drivers.²⁹,³⁰

Few outside of the liver community recognise the need to deliver whole-of-society public health responses to fatty liver disease.³¹⁻³³ In 2021, a global consortium of experts set out consensus recommendations on how to accelerate public health action on this issue.³⁴ The negative impact of the COVID-19 pandemic on fatty liver disease risk factors³⁵,³⁶ further reinforces the urgent attention this public health threat requires.

The liver health community (i.e., the people and organisations who are largely working to improve liver health) must now build on past efforts to develop a clear vision and pathway to reduce the burden and address the individual and societal impacts of this growing challenge. Research is the central pivot for these efforts, accelerating the pace of knowledge creation and its translation into policy and practice.³⁷⁻³⁹

# Materials and methods

## Delphi expert panel member sample

The study's nine co-chairs used an iterative approach involving purposive, snowball, and targeted sampling to generate a large, global panel for this Delphi study. Based on publication record and engagement with the fatty liver disease agenda, the co-chairs identified 31 experts in clinical care (e.g., liver, diabetes, obesity, and nutrition), public health, policy, advocacy, and patient representation, who collectively formed the core author group (n = 40) (Table S1). The proposed survey panel (n = 473) was created by

compiling a list of known fatty liver disease experts from around the world with input from the core group (Fig. 1). Through this process, an expert panel diverse in demographic, disciplinary, and geographical characteristics was obtained (Table 1).

## Delphi statement domains

The development of the research priorities started with the core author group leading the development of evidence notes around seven topics, summarising the current knowledge base, envisioning what 'success' would look like in the next decade, identifying key questions, and suggesting research priorities for: (1) the human and economic burden, (2) defining and implementing models of care, (3) treatment and care, (4) education and awareness, (5) patient and community perspectives, (6) policy strategies and a societal approach, and (7) leadership for the fatty liver disease public health agenda. Twenty-six of the core-group members and 11 co-authors held a three-day meeting at Wilton Park, UK, in October 2022, co-chaired by H.E.M and opened by T.B and J.V.L, as part of the process. The research priorities were subsequently revised by J.V.L and H.E.M to reflect the Wilton Park discussions, and topics 6 and 7 were combined. The full core group received revised priorities for review in December 2022, with further revisions made based on core group feedback ahead of the first Delphi survey round (21 December 2022 to 15 January 2023).

## Delphi method data collection and analysis

The study design consisted of an in-person Wilton Park meeting (Table S2) and two survey rounds (R1 and R2) wherein panellists reviewed and voted on the research priorities. The study used the Qualtrics XM platform to develop and distribute the surveys (round duration ranged from 2 to 3.5 weeks), which included four-point Likert-type response categories for measuring the level of agreement with the draft research priorities (i.e., 'agree', 'somewhat agree', 'somewhat disagree', and 'disagree'); the survey included a fifth 'not qualified to respond' option to accommodate the broad range of knowledge and expertise across panel participants. Panellists could provide comments and suggest edits to individual priorities in text boxes, which followed each of the statements. Both R1 and R2 included a text box allowing for overall comments at the end of each survey. Demographic data were collected from participants in R1.

An analytic team comprised of a sub-set of the core group (J.V.L, H.E.M, P.N.B, C.J.K, D.R, D.I.W, and M.V-R) reviewed the R1 data, including 600 open-ended comments from the panellists, and initiated draft revisions. The full core group then reviewed the revised priorities. In R2 (8-21 February 2023), panellists voted on the revised priorities, which were accompanied by text boxes summarising changes made based on panellist and core group input from R1. Panellists also ranked at least half of the priorities within each of the six domains; for domains with only three priorities panellists ranked all three.

Quantitative analysis of the R1 and R2 results included frequencies and proportions of the four response categories spanning 'agree' to 'disagree' for all research priority statements, as well as those selecting 'not qualified to respond'. For the final R2 Delphi results, we assigned each research priority statement with a grade to indicate the level of combined

### Box 1. The evolution of fatty liver disease nomenclature.¹²

The relationship between fatty liver disease, obesity, and diabetes was first described in the mid-1900s. Until then, the distinction between alcohol-related and non-alcoholic fatty liver disease (NAFLD) had been uncommon. In 1980, Ludwig *et al.* coined the term non-alcoholic steatohepatitis (NASH),¹² with NAFLD being a widely used umbrella term describing a histological spectrum ranging from steatosis without inflammation, to steatosis with varying degrees of inflammation and hepatocellular ballooning, which can lead to fibrosis, cirrhosis, and hepatocellular carcinoma. Recently, several proposals have been made to change the disease name, moving away from the construct of 'non-alcoholic' and better reflecting the metabolic foundation of the disease's aetiology. In 2023, a global consensus process is ongoing to reach agreement on the disease nomenclature. In this paper, we refer to fatty liver disease which arises in the absence of heavy alcohol intake and independently of other liver diseases.
symptoms often leads to a clinically relevant delay in diagnosis.¹⁷,¹⁸ Non-invasive tests (NITs) provide a practical and safe way of assessing fibrosis severity¹⁹ and the risk of future liver-related events.²⁰,²¹ NITs have been used in the development of pathways to identify and stratify patients based on care needs,²²⁻²⁵ yet such pathways are not implemented in the majority of healthcare settings.¹⁶

Several pharmacological treatments are under development, with some in late-stage clinical trials.²⁶,²⁷ However, India is the only country where regulators have approved a pharmacological treatment for routine use in fatty liver disease (saroglitazar).²⁸ In the absence of pharmacological treatments approved for NASH, management is focused on improving insulin resistance and weight loss, when needed, and on attenuating the pro-inflammatory milieu of obesity, which are the predominant disease drivers.²⁹,³⁰

Few outside of the liver community recognise the need to deliver whole-of-society public health responses to fatty liver disease.³¹⁻³³ In 2021, a global consortium of experts set out consensus recommendations on how to accelerate public health action on this issue.³⁴ The negative impact of the COVID-19 pandemic on fatty liver disease risk factors³⁵,³⁶ further reinforces the urgent attention this public health threat requires.

The liver health community (i.e., the people and organisations who are largely working to improve liver health) must now build on past efforts to develop a clear vision and pathway to reduce the burden and address the individual and societal impacts of this growing challenge. Research is the central pivot for these efforts, accelerating the pace of knowledge creation and its translation into policy and practice.³⁷⁻³⁹

# Materials and methods

## Delphi expert panel member sample

The study's nine co-chairs used an iterative approach involving purposive, snowball, and targeted sampling to generate a large, global panel for this Delphi study. Based on publication record and engagement with the fatty liver disease agenda, the co-chairs identified 31 experts in clinical care (e.g., liver, diabetes, obesity, and nutrition), public health, policy, advocacy, and patient representation, who collectively formed the core author group (n = 40) (Table S1). The proposed survey panel (n = 473) was created by

compiling a list of known fatty liver disease experts from around the world with input from the core group (Fig. 1). Through this process, an expert panel diverse in demographic, disciplinary, and geographical characteristics was obtained (Table 1).

## Delphi statement domains

The development of the research priorities started with the core author group leading the development of evidence notes around seven topics, summarising the current knowledge base, envisioning what 'success' would look like in the next decade, identifying key questions, and suggesting research priorities for: (1) the human and economic burden, (2) defining and implementing models of care, (3) treatment and care, (4) education and awareness, (5) patient and community perspectives, (6) policy strategies and a societal approach, and (7) leadership for the fatty liver disease public health agenda. Twenty-six of the core-group members and 11 co-authors held a three-day meeting at Wilton Park, UK, in October 2022, co-chaired by H.E.M and opened by T.B and J.V.L, as part of the process. The research priorities were subsequently revised by J.V.L and H.E.M to reflect the Wilton Park discussions, and topics 6 and 7 were combined. The full core group received revised priorities for review in December 2022, with further revisions made based on core group feedback ahead of the first Delphi survey round (21 December 2022 to 15 January 2023).

## Delphi method data collection and analysis

The study design consisted of an in-person Wilton Park meeting (Table S2) and two survey rounds (R1 and R2) wherein panellists reviewed and voted on the research priorities. The study used the Qualtrics XM platform to develop and distribute the surveys (round duration ranged from 2 to 3.5 weeks), which included four-point Likert-type response categories for measuring the level of agreement with the draft research priorities (i.e., 'agree', 'somewhat agree', 'somewhat disagree', and 'disagree'); the survey included a fifth 'not qualified to respond' option to accommodate the broad range of knowledge and expertise across panel participants. Panellists could provide comments and suggest edits to individual priorities in text boxes, which followed each of the statements. Both R1 and R2 included a text box allowing for overall comments at the end of each survey. Demographic data were collected from participants in R1.

An analytic team comprised of a sub-set of the core group (J.V.L, H.E.M, P.N.B, C.J.K, D.R, D.I.W, and M.V-R) reviewed the R1 data, including 600 open-ended comments from the panellists, and initiated draft revisions. The full core group then reviewed the revised priorities. In R2 (8-21 February 2023), panellists voted on the revised priorities, which were accompanied by text boxes summarising changes made based on panellist and core group input from R1. Panellists also ranked at least half of the priorities within each of the six domains; for domains with only three priorities panellists ranked all three.

Quantitative analysis of the R1 and R2 results included frequencies and proportions of the four response categories spanning 'agree' to 'disagree' for all research priority statements, as well as those selecting 'not qualified to respond'. For the final R2 Delphi results, we assigned each research priority statement with a grade to indicate the level of combined

### Box 1. The evolution of fatty liver disease nomenclature.¹²

The relationship between fatty liver disease, obesity, and diabetes was first described in the mid-1900s. Until then, the distinction between alcohol-related and non-alcoholic fatty liver disease (NAFLD) had been uncommon. In 1980, Ludwig *et al.* coined the term non-alcoholic steatohepatitis (NASH),¹² with NAFLD being a widely used umbrella term describing a histological spectrum ranging from steatosis without inflammation, to steatosis with varying degrees of inflammation and hepatocellular ballooning, which can lead to fibrosis, cirrhosis, and hepatocellular carcinoma. Recently, several proposals have been made to change the disease name, moving away from the construct of 'non-alcoholic' and better reflecting the metabolic foundation of the disease's aetiology. In 2023, a global consensus process is ongoing to reach agreement on the disease nomenclature. In this paper, we refer to fatty liver disease which arises in the absence of heavy alcohol intake and independently of other liver diseases.
Global research priority agenda for fatty liver disease

<figure><img src="image_6.png" /><figcaption>**Fig. 1.** Delphi panel generation and data collection. Study methodology, including sample and data collection. Top, the iterative sampling approach used to generate a large and diverse Delphi panel (n = 344): nine co-chairs identified a core group of 31 experts in clinical care, public health, policy, and advocacy, who collectively formed the core authorship group (n = 40), working across 20 countries; the core group identified individuals with expertise in the fatty liver disease field. Bottom, the iterative digital data-collection process, including priority drafting (by the study co-chairs) and revision (by the co-chairs and other core authors) of the statements; one survey round (R1) of draft statements; analysis and revision of the statements by the core group; and a revised and final survey round (R2) of the consensus statements. R1 included text boxes for panellists to provide comments and suggest edits to individual statements; the final round (R2) allowed for overall comments at the end of each domain. For the final set of statements in R2, panellists ranked at least the top half of recommendations in each of the six domains. *For domains with three priorities, panellists were required to rank them all. RR, response rate.*</figcaption></figure>

agreement (agree' + somewhat agree), using a system that has been used in other Delphi studies³⁴,⁴⁰,⁴¹ in which 'U' denotes unanimous (100%) agreement, 'A' denotes 90-99% combined agreement, 'B' denotes 78-89% combined agreement, and 'C' denotes 67-77% combined agreement. The data tables report the proportion who selected 'not qualified to respond', who were removed from the denominator to calculate the levels of agreement/disagreement from the relevant sample.

For the ranking, scores were calculated and normalised in Microsoft Excel (v.16.70) to compare rankings within each domain. Demographic data were analysed descriptively, including frequencies and proportions. No data were excluded from any analyses. Instances of missing data were totalled, and denominators were adjusted as applicable, for any calculations involving missing datapoints.

Ethical considerations

As this study does not include patients, patient data, or biological human samples, it received ethical review exemption from the Hospital Clínic of Barcelona, Spain, ethics committee on 19 December 2022. Each participant was asked to consent to participating in the study, prior to their inclusion. Adequate measures to ensure personal data protection and confidentiality have been taken and data were deidentified for all analyses.

Results

A total of 473 individuals were invited to participate in R1 and 344 (72.7%) completed the survey. These 344 respondents

were invited to participate in R2, of whom 288 (83.7%) completed the survey. Table 1 details the demographics of all expert panellists involved in the study. The mean age of respondents was 53.8 (standard deviation: 10.1). Most respondents were male (64.8%), worked in high-income countries (69.9%) and in the Europe and Central Asia region (42.2%), were primarily employed in the academic sector (66.6%), and worked in the clinical research field (79.4%). A total of 94 countries were represented in terms of respondent country of origin and 91 in terms of respondent country of work.

In R1, the study presented 31 initial research priorities to the panel. During revisions ahead of R2, three priorities were removed, with key components of these original statements being merged with existing priorities, leaving 28 priorities for the panel to review in R2. Across the two Delphi rounds, consensus increased for all six domains. The mean percentage of 'agree' responses across domains increased from 78.3 in R1 to 81.1 in R2, following the consideration of substantive comments received in R1.

Table 2 presents the final priorities, agreement grades, and rankings for each of the six domains. Within the final priorities in R2 (Fig. 2), the panel reached a unanimous combined agreement ('agree' + 'somewhat agree') with five priorities and >90% combined agreement with the remaining 23; the mean level of combined agreement across all priorities was 97.7%. For 13 priorities, 'agree' answers were below 80%, with higher reliance on 'somewhat agree' to achieve the high rate of overall combined agreement (Table S3).
## Global research priority agenda for fatty liver disease

<figure><img src="image_5.png" /><figcaption>**Fig. 1.** Delphi panel generation and data collection. Study methodology, including sample and data collection. Top, the iterative sampling approach used to generate a large and diverse Delphi panel (n = 344): nine co-chairs identified a core group of 31 experts in clinical care, public health, policy, and advocacy, who collectively formed the core authorship group (n = 40), working across 20 countries; the core group identified individuals with expertise in the fatty liver disease field. Bottom, the iterative digital data-collection process, including priority drafting (by the study co-chairs) and revision (by the co-chairs and other core authors) of the statements; one survey round (R1) of draft statements; analysis and revision of the statements by the core group; and a revised and final survey round (R2) of the consensus statements. R1 included text boxes for panellists to provide comments and suggest edits to individual statements; the final round (R2) allowed for overall comments at the end of each domain. For the final set of statements in R2, panellists ranked at least the top half of recommendations in each of the six domains. *For domains with three priorities, panellists were required to rank them all. RR, response rate.*</figcaption></figure>

agreement (agree' + somewhat agree), using a system that has been used in other Delphi studies<sup>34,40,41</sup> in which 'U' denotes unanimous (100%) agreement, 'A' denotes 90-99% combined agreement, 'B' denotes 78-89% combined agreement, and 'C' denotes 67-77% combined agreement. The data tables report the proportion who selected 'not qualified to respond', who were removed from the denominator to calculate the levels of agreement/disagreement from the relevant sample.

For the ranking, scores were calculated and normalised in Microsoft Excel (v.16.70) to compare rankings within each domain. Demographic data were analysed descriptively, including frequencies and proportions. No data were excluded from any analyses. Instances of missing data were totalled, and denominators were adjusted as applicable, for any calculations involving missing datapoints.

### Ethical considerations

As this study does not include patients, patient data, or biological human samples, it received ethical review exemption from the Hospital Clínic of Barcelona, Spain, ethics committee on 19 December 2022. Each participant was asked to consent to participating in the study, prior to their inclusion. Adequate measures to ensure personal data protection and confidentiality have been taken and data were deidentified for all analyses.

### Results

A total of 473 individuals were invited to participate in R1 and 344 (72.7%) completed the survey. These 344 respondents

were invited to participate in R2, of whom 288 (83.7%) completed the survey. Table 1 details the demographics of all expert panellists involved in the study. The mean age of respondents was 53.8 (standard deviation: 10.1). Most respondents were male (64.8%), worked in high-income countries (69.9%) and in the Europe and Central Asia region (42.2%), were primarily employed in the academic sector (66.6%), and worked in the clinical research field (79.4%). A total of 94 countries were represented in terms of respondent country of origin and 91 in terms of respondent country of work.

In R1, the study presented 31 initial research priorities to the panel. During revisions ahead of R2, three priorities were removed, with key components of these original statements being merged with existing priorities, leaving 28 priorities for the panel to review in R2. Across the two Delphi rounds, consensus increased for all six domains. The mean percentage of 'agree' responses across domains increased from 78.3 in R1 to 81.1 in R2, following the consideration of substantive comments received in R1.

Table 2 presents the final priorities, agreement grades, and rankings for each of the six domains. Within the final priorities in R2 (Fig. 2), the panel reached a unanimous combined agreement ('agree' + 'somewhat agree') with five priorities and >90% combined agreement with the remaining 23; the mean level of combined agreement across all priorities was 97.7%. For 13 priorities, 'agree' answers were below 80%, with higher reliance on 'somewhat agree' to achieve the high rate of overall combined agreement (Table S3).
<table><caption>Table 1. Delphi panel characteristics (n = 344).</caption><thead><tr><th>Characteristic</th><th>n (%)</th></tr></thead><tbody><tr><td><strong>Gender</strong></td><td></td></tr><tr><td>Woman</td><td>115 (33.7)</td></tr><tr><td>Man</td><td>221 (64.8)</td></tr><tr><td>Non-binary or gender diverse</td><td>3 (0.9)</td></tr><tr><td>Prefer not to say</td><td>2 (0.6)</td></tr><tr><td>No response</td><td>3 (0.9)</td></tr><tr><td><strong>Age</strong></td><td></td></tr><tr><td>All, mean [SD]</td><td>53.8 [10.1]</td></tr><tr><td>No response</td><td>12 (3.5)</td></tr><tr><td><strong>Country of origin, by income level (n = 94)</strong></td><td></td></tr><tr><td>Low or middle</td><td>124 (36.9)</td></tr><tr><td>High</td><td>212 (63.1)</td></tr><tr><td>No response</td><td>8 (2.3)</td></tr><tr><td><strong>Global region<sup>a</sup> of origin</strong></td><td></td></tr><tr><td>East Asia and Pacific</td><td>37 (11.0)</td></tr><tr><td>Europe and Central Asia<sup>b</sup></td><td>142 (42.3)</td></tr><tr><td>Latin America and Caribbean</td><td>41 (12.2)</td></tr><tr><td>Middle East and North Africa</td><td>28 (8.3)</td></tr><tr><td>North America</td><td>52 (15.5)</td></tr><tr><td>South Asia</td><td>19 (5.7)</td></tr><tr><td>Sub-Saharan Africa</td><td>17 (5.1)</td></tr><tr><td>No response</td><td>8 (2.3)</td></tr><tr><td><strong>Country of work, by income level (n = 91)</strong></td><td></td></tr><tr><td>Low or middle</td><td>102 (30.1)</td></tr><tr><td>High</td><td>237 (69.9)</td></tr><tr><td>No response</td><td>5 (1.5)</td></tr><tr><td><strong>Global region<sup>a</sup> of work</strong></td><td></td></tr><tr><td>East Asia and Pacific</td><td>36 (10.6)</td></tr><tr><td>Europe and Central Asia<sup>c</sup></td><td>143 (42.2)</td></tr><tr><td>Latin America and Caribbean</td><td>34 (10.0)</td></tr><tr><td>Middle East and North Africa</td><td>24 (7.1)</td></tr><tr><td>North America</td><td>76 (22.4)</td></tr><tr><td>South Asia</td><td>12 (3.5)</td></tr><tr><td>Sub-Saharan Africa</td><td>14 (4.1)</td></tr><tr><td>No response</td><td>5 (1.5)</td></tr><tr><td><strong>Primary sector of employment<sup>d</sup></strong></td><td></td></tr><tr><td>Academic</td><td>229 (66.6)</td></tr><tr><td>Public</td><td>62 (18.0)</td></tr><tr><td>Private</td><td>38 (11.0)</td></tr><tr><td>Civil society</td><td>9 (2.6)</td></tr><tr><td>Other</td><td>3 (0.9)</td></tr><tr><td>No response</td><td>3 (0.9)</td></tr><tr><td><strong>Field(s) of employment<sup>d,e</sup></strong></td><td></td></tr><tr><td>Clinical research</td><td>273 (79.4)</td></tr><tr><td>Non-clinical research</td><td>81 (23.5)</td></tr><tr><td>Healthcare provider</td><td>180 (52.3)</td></tr><tr><td>Patient/policy advocacy</td><td>36 (10.5)</td></tr><tr><td>Education</td><td>10 (2.9)</td></tr><tr><td>Other</td><td>7 (2.0)</td></tr><tr><td>No response</td><td>3 (0.9)</td></tr><tr><td><strong>Years working in fatty liver disease field</strong></td><td></td></tr><tr><td>1 to 11</td><td>148 (43.7)</td></tr><tr><td>12 to 22</td><td>132 (38.9)</td></tr><tr><td>23 to 33</td><td>49 (14.5)</td></tr><tr><td>34 to 44</td><td>8 (2.4)</td></tr><tr><td>45 to 55</td><td>2 (0.6)</td></tr><tr><td>No response</td><td>5 (1.5)</td></tr><tr><td><strong>Publications authored focused on fatty liver disease</strong></td><td></td></tr><tr><td>&lt;6</td><td>103 (30.9)</td></tr><tr><td>6 to 25</td><td>95 (28.5)</td></tr><tr><td>26 to 50</td><td>54 (16.2)</td></tr><tr><td>51 to 100</td><td>42 (12.6)</td></tr><tr><td>&gt;100</td><td>39 (11.7)</td></tr><tr><td>No response</td><td>11 (3.2)</td></tr></tbody></table>

(continued)

<table><caption>Table 1. (continued)</caption><thead><tr><th>Characteristic</th><th>n (%)</th></tr></thead><tbody><tr><td><strong>International or regional liver association membership(s)<sup>e</sup></strong></td><td></td></tr><tr><td>AASLD</td><td>165 (48.0)</td></tr><tr><td>APASL</td><td>34 (9.9)</td></tr><tr><td>ALEH</td><td>30 (8.7)</td></tr><tr><td>EASL</td><td>191 (55.5)</td></tr><tr><td>Other</td><td>18 (5.2)</td></tr><tr><td>No membership</td><td>152 (44.2)</td></tr><tr><td><strong>Area of national professional association/society membership(s) in country of work<sup>e</sup></strong></td><td></td></tr><tr><td>Liver disease</td><td>254 (73.8)</td></tr><tr><td>Gastroenterology</td><td>184 (53.5)</td></tr><tr><td>Obesity</td><td>42 (12.2)</td></tr><tr><td>Diabetes/endocrinology</td><td>45 (13.1)</td></tr><tr><td>Heart disease</td><td>11 (3.2)</td></tr><tr><td>Cancer</td><td>15 (4.4)</td></tr><tr><td>Primary care</td><td>5 (1.5)</td></tr><tr><td>Other</td><td>26 (7.6)</td></tr><tr><td>No membership</td><td>25 (7.3)</td></tr></tbody></table>

Percentages may sum to >100 due to rounding. Percentages for 'no response' are based on the total number of participants; all other percentages are calculated after excluding n of no response, unless otherwise indicated. AASLD, American Association for the Study of Liver Diseases; APASL, Asian Pacific Association for the Study of the Liver; ALEH, Asociación Latinoamericana para el Estudio del Higado (Latin American Association for the Study of the Liver); EASL, European Association for the Study of the Liver.

<sup>a</sup>Based on World Bank regions.

<sup>b</sup>n = 3 participants are originally from Central Asia.

<sup>c</sup>n = 3 participants work in Central Asia.

<sup>d</sup>Denominator includes n of no response.

<sup>e</sup>Sum may exceed sample size as participants could choose >1 response.

Patient and community perspectives was one of two domains within the study where more than half of the research priority statements had <80% of the panel 'agree.' Five of six statements (5.1 and 5.3-5.6) illustrated higher reliance on 'somewhat agree' to achieve >90% combined agreement. Leadership and public health policies was the second domain where more than half of the research priority statements had <80% of the panel 'agree.' Two of three statements (6.1 and 6.3) illustrated higher reliance on 'somewhat agree' to achieve >90% combined agreement.

The priority rankings are explored in the discussion, alongside a summary of current evidence within each area.

Discussion

This study engaged a multi-disciplinary group of experts and leaders from around the world to develop a consensus research agenda that is ambitious and transformational in nature and can deliver a step-change in how fatty liver disease is prevented and managed. To achieve this change, the study not only puts forward a shared research vision, but also illuminates degrees of agreement within the fatty liver disease community of practice, underscoring the benefit of continued discussion throughout the community. Here, we explore the importance of the research priorities for advancing the field with a focus on the highest ranked priorities across the six fatty liver disease research domains. The high response rates across both survey rounds and the substantial, often near-unanimous agreement of the panellists on all priorities suggests that agreeing on research priorities, for the first time in the fatty liver disease field, was a meaningful and important undertaking that builds on early priority-setting efforts.⁴²,⁴³
<table><caption>Table 1. Delphi panel characteristics (n = 344).</caption><thead><tr><th>Characteristic</th><th>n (%)</th></tr></thead><tbody><tr><td><strong>Gender</strong></td><td></td></tr><tr><td>Woman</td><td>115 (33.7)</td></tr><tr><td>Man</td><td>221 (64.8)</td></tr><tr><td>Non-binary or gender diverse</td><td>3 (0.9)</td></tr><tr><td>Prefer not to say</td><td>2 (0.6)</td></tr><tr><td>No response</td><td>3 (0.9)</td></tr><tr><td><strong>Age</strong></td><td></td></tr><tr><td>All, mean [SD]</td><td>53.8 [10.1]</td></tr><tr><td>No response</td><td>12 (3.5)</td></tr><tr><td><strong>Country of origin, by income level (n = 94)</strong></td><td></td></tr><tr><td>Low or middle</td><td>124 (36.9)</td></tr><tr><td>High</td><td>212 (63.1)</td></tr><tr><td>No response</td><td>8 (2.3)</td></tr><tr><td><strong>Global region<sup>a</sup> of origin</strong></td><td></td></tr><tr><td>East Asia and Pacific</td><td>37 (11.0)</td></tr><tr><td>Europe and Central Asia<sup>b</sup></td><td>142 (42.3)</td></tr><tr><td>Latin America and Caribbean</td><td>41 (12.2)</td></tr><tr><td>Middle East and North Africa</td><td>28 (8.3)</td></tr><tr><td>North America</td><td>52 (15.5)</td></tr><tr><td>South Asia</td><td>19 (5.7)</td></tr><tr><td>Sub-Saharan Africa</td><td>17 (5.1)</td></tr><tr><td>No response</td><td>8 (2.3)</td></tr><tr><td><strong>Country of work, by income level (n = 91)</strong></td><td></td></tr><tr><td>Low or middle</td><td>102 (30.1)</td></tr><tr><td>High</td><td>237 (69.9)</td></tr><tr><td>No response</td><td>5 (1.5)</td></tr><tr><td><strong>Global region<sup>a</sup> of work</strong></td><td></td></tr><tr><td>East Asia and Pacific</td><td>36 (10.6)</td></tr><tr><td>Europe and Central Asia<sup>c</sup></td><td>143 (42.2)</td></tr><tr><td>Latin America and Caribbean</td><td>34 (10.0)</td></tr><tr><td>Middle East and North Africa</td><td>24 (7.1)</td></tr><tr><td>North America</td><td>76 (22.4)</td></tr><tr><td>South Asia</td><td>12 (3.5)</td></tr><tr><td>Sub-Saharan Africa</td><td>14 (4.1)</td></tr><tr><td>No response</td><td>5 (1.5)</td></tr><tr><td><strong>Primary sector of employment<sup>d</sup></strong></td><td></td></tr><tr><td>Academic</td><td>229 (66.6)</td></tr><tr><td>Public</td><td>62 (18.0)</td></tr><tr><td>Private</td><td>38 (11.0)</td></tr><tr><td>Civil society</td><td>9 (2.6)</td></tr><tr><td>Other</td><td>3 (0.9)</td></tr><tr><td>No response</td><td>3 (0.9)</td></tr><tr><td><strong>Field(s) of employment<sup>d,e</sup></strong></td><td></td></tr><tr><td>Clinical research</td><td>273 (79.4)</td></tr><tr><td>Non-clinical research</td><td>81 (23.5)</td></tr><tr><td>Healthcare provider</td><td>180 (52.3)</td></tr><tr><td>Patient/policy advocacy</td><td>36 (10.5)</td></tr><tr><td>Education</td><td>10 (2.9)</td></tr><tr><td>Other</td><td>7 (2.0)</td></tr><tr><td>No response</td><td>3 (0.9)</td></tr><tr><td><strong>Years working in fatty liver disease field</strong></td><td></td></tr><tr><td>1 to 11</td><td>148 (43.7)</td></tr><tr><td>12 to 22</td><td>132 (38.9)</td></tr><tr><td>23 to 33</td><td>49 (14.5)</td></tr><tr><td>34 to 44</td><td>8 (2.4)</td></tr><tr><td>45 to 55</td><td>2 (0.6)</td></tr><tr><td>No response</td><td>5 (1.5)</td></tr><tr><td><strong>Publications authored focused on fatty liver disease</strong></td><td></td></tr><tr><td>&lt;6</td><td>103 (30.9)</td></tr><tr><td>6 to 25</td><td>95 (28.5)</td></tr><tr><td>26 to 50</td><td>54 (16.2)</td></tr><tr><td>51 to 100</td><td>42 (12.6)</td></tr><tr><td>&gt;100</td><td>39 (11.7)</td></tr><tr><td>No response</td><td>11 (3.2)</td></tr></tbody></table>

(continued)

<table><caption>Table 1. (continued)</caption><thead><tr><th>Characteristic</th><th>n (%)</th></tr></thead><tbody><tr><td><strong>International or regional liver association membership(s)<sup>e</sup></strong></td><td></td></tr><tr><td>AASLD</td><td>165 (48.0)</td></tr><tr><td>APASL</td><td>34 (9.9)</td></tr><tr><td>ALEH</td><td>30 (8.7)</td></tr><tr><td>EASL</td><td>191 (55.5)</td></tr><tr><td>Other</td><td>18 (5.2)</td></tr><tr><td>No membership</td><td>152 (44.2)</td></tr><tr><td><strong>Area of national professional association/society membership(s) in country of work<sup>e</sup></strong></td><td></td></tr><tr><td>Liver disease</td><td>254 (73.8)</td></tr><tr><td>Gastroenterology</td><td>184 (53.5)</td></tr><tr><td>Obesity</td><td>42 (12.2)</td></tr><tr><td>Diabetes/endocrinology</td><td>45 (13.1)</td></tr><tr><td>Heart disease</td><td>11 (3.2)</td></tr><tr><td>Cancer</td><td>15 (4.4)</td></tr><tr><td>Primary care</td><td>5 (1.5)</td></tr><tr><td>Other</td><td>26 (7.6)</td></tr><tr><td>No membership</td><td>25 (7.3)</td></tr></tbody></table>

Percentages may sum to >100 due to rounding. Percentages for 'no response' are based on the total number of participants; all other percentages are calculated after excluding n of no response, unless otherwise indicated. AASLD, American Association for the Study of Liver Diseases; APASL, Asian Pacific Association for the Study of the Liver; ALEH, Asociación Latinoamericana para el Estudio del Higado (Latin American Association for the Study of the Liver); EASL, European Association for the Study of the Liver.

<sup>a</sup>Based on World Bank regions.

<sup>b</sup>n = 3 participants are originally from Central Asia.

<sup>c</sup>n = 3 participants work in Central Asia.

<sup>d</sup>Denominator includes n of no response.

<sup>e</sup>Sum may exceed sample size as participants could choose >1 response.

Patient and community perspectives was one of two domains within the study where more than half of the research priority statements had <80% of the panel 'agree.' Five of six statements (5.1 and 5.3-5.6) illustrated higher reliance on 'somewhat agree' to achieve >90% combined agreement. Leadership and public health policies was the second domain where more than half of the research priority statements had <80% of the panel 'agree.' Two of three statements (6.1 and 6.3) illustrated higher reliance on 'somewhat agree' to achieve >90% combined agreement.

The priority rankings are explored in the discussion, alongside a summary of current evidence within each area.

Discussion

This study engaged a multi-disciplinary group of experts and leaders from around the world to develop a consensus research agenda that is ambitious and transformational in nature and can deliver a step-change in how fatty liver disease is prevented and managed. To achieve this change, the study not only puts forward a shared research vision, but also illuminates degrees of agreement within the fatty liver disease community of practice, underscoring the benefit of continued discussion throughout the community. Here, we explore the importance of the research priorities for advancing the field with a focus on the highest ranked priorities across the six fatty liver disease research domains. The high response rates across both survey rounds and the substantial, often near-unanimous agreement of the panellists on all priorities suggests that agreeing on research priorities, for the first time in the fatty liver disease field, was a meaningful and important undertaking that builds on early priority-setting efforts.⁴²,⁴³
## Building the case for action: a better understanding of the human and economic burden

Knowledge of fatty liver disease has advanced tremendously over the past three decades, including on the predominant risk factors and disease drivers, yet gaps remain in our understanding of its natural history.⁴⁴ Most studies on its natural history and clinical progression emerge from tertiary centres, registries, or are based on biopsy availability,⁴⁵⁻⁴⁷ which introduces disease-spectrum bias, while few are from prospective unbiased cohorts. As the field seeks to advance understanding, the panel specifically prioritised cohort studies that prospectively monitor outcomes in patients with defined liver disease (priority 1.2; ranked 1st in its domain); such cohorts will ideally be sampled from the general population.

In a separate but related priority, the panel unanimously supported the development and validation of risk prediction models to forecast progressive hepatic and extrahepatic outcomes (priority 1.4; ranked 3rd in its domain). The few risk-prediction models currently in use focus on broad risk factors, such as diabetes and body mass index. Future efforts will lead toward more nuanced predictors of outcomes, including novel biomarkers, as part of the quest towards precision medicine.⁴³,⁴⁸

While notable efforts have been made to establish the disease prevalence in both adults and children,¹⁻³,⁴⁸ there are critical knowledge gaps in most countries and regions. The panel prioritised additional studies to better quantify the overall burden, including the disease prevalence and the quality of life impairment, in the general population and in high-risk groups (priority 1.1; ranked 2nd in its domain).

The panel almost universally agreed that additional studies are necessary to better quantify both the direct and indirect costs of fatty liver disease (priority 1.3). Available studies, while showing substantial costs associated with the disease,¹⁰,¹¹,⁴⁹,⁵⁰ are limited to a small number of high-income countries. Of equal importance to the panel was to advance understanding of the factors driving inequities in fatty liver disease (priority 1.5). The limited data in existence highlight large inequities by social group⁵¹ and mirror what is seen more widely with non-communicable diseases (NCDs).⁵² Further elucidating these factors will support the development of more targeted approaches to prevent and manage the burden of fatty liver disease.

## Advancing health system responses to fatty liver disease

### Defining and implementing multidisciplinary models of care

One of the greatest challenges in clinical practice remains the identification of those with fatty liver disease and subsequent risk-stratification of those needing aggressive intervention and close monitoring by a specialist, from those who can be managed in primary care. Great advances have been made on the use of NITs in the past decades⁴⁸,⁵³,⁵⁴ and there is increasingly robust evidence of the value of current NITs for prognostication,²⁰,²¹ yet substantial challenges remain.⁵⁵ There is a critical unmet need when it comes to non-invasive approaches for monitoring disease progression and assessing disease resolution or meaningful improvements in fibrosis.⁴⁸,⁵⁶,⁵⁷ The panel unanimously recognised this imperative and gave a high priority to further validating NITs, with a focus on enabling early diagnosis, prognosis, and monitoring of

liver disease progression (priority 2.4; ranked 1st in its domain). Within this, emphasis will be needed on the cost-effectiveness of different approaches within different resource environments¹⁹,⁵⁸,⁵⁹ and the appropriate cut-offs to be used in different settings and population groups.⁶⁰

The multisystem nature of fatty liver disease, and the fact that many patients present with a range of comorbidities, requires a multi-disciplinary approach to management and care;¹⁶,⁶¹,⁶² however, multi-disciplinary care models have not been widely adopted in most healthcare settings.¹⁶ The panel unanimously called for further studies to determine the effectiveness of different models of care, including the impact on patient outcomes and their cost-effectiveness (priority 2.1; ranked 2nd in its domain). As this work advances, emphasis should be placed on care models that can be adaptable and implementable based on local resources. Specific considerations are needed around care models for paediatric populations (priority 2.2).⁶³⁻⁶⁶

Alongside the development of effective care models, the heterogeneity of patient presentation, coupled with the large burden of disease, means that tools are needed to support clinicians to identify those at highest risk of disease progression and adverse outcomes. The panel stressed the need to validate risk prediction models in different population groups, enabling them to be tailored to specific groups (priority 2.3; ranked 3rd in its domain).

The use of digital technologies in healthcare settings holds great potential for supporting service delivery,⁶⁷ yet this is a relatively new area of research within the field of fatty liver disease.⁶⁸⁻⁷¹ The panel supported the exploration of how novel digital technologies can be utilised within healthcare settings (priority 2.5) and further exploration of the potential for artificial intelligence methods to improve diagnosis of fatty liver disease (priority 2.7). The panel also supported further understanding how digital health approaches can support patients to achieve lifestyle behavioural change (priority 2.6). This work can build upon and complement broader efforts within the NCD and mental health fields.⁷²,⁷³

### Accelerating advances in fatty liver disease treatment

In advancing treatment and care for affected populations, the panel highly ranked the importance of understanding the role of NITs in guiding treatment indication, response, and discontinuation, as well as predicting outcomes (priority 3.2; ranked 1st in its domain). This priority speaks to the current gap in evidence on the use of NITs to gain information on therapeutic responses.⁴⁸,⁷⁴ As specific therapeutics are approved, NITs which can guide treatment decisions will be critical, especially given the likely long duration and high cost of treatment.

Currently, the central focus of treatment for fatty liver disease has been lifestyle interventions (e.g., nutrition, exercise, and weight loss), pharmacological treatment of comorbidities such as obesity and diabetes, and liver-directed therapies. The panel acknowledged that the prevention of fatty liver disease-related cirrhosis or HCC will require multi-pronged strategies which address an array of risk factors (e.g., social, environmental, behavioural, biological, and genetic) and called for studies to assess the efficacy and cost-effectiveness of such strategies (priority 3.1; ranked 2nd in its domain). As fatty liver disease treatment options expand, patient-centred decision
## Building the case for action: a better understanding of the human and economic burden

Knowledge of fatty liver disease has advanced tremendously over the past three decades, including on the predominant risk factors and disease drivers, yet gaps remain in our understanding of its natural history.⁴⁴ Most studies on its natural history and clinical progression emerge from tertiary centres, registries, or are based on biopsy availability,⁴⁵⁻⁴⁷ which introduces disease-spectrum bias, while few are from prospective unbiased cohorts. As the field seeks to advance understanding, the panel specifically prioritised cohort studies that prospectively monitor outcomes in patients with defined liver disease (priority 1.2; ranked 1st in its domain); such cohorts will ideally be sampled from the general population.

In a separate but related priority, the panel unanimously supported the development and validation of risk prediction models to forecast progressive hepatic and extrahepatic outcomes (priority 1.4; ranked 3rd in its domain). The few risk-prediction models currently in use focus on broad risk factors, such as diabetes and body mass index. Future efforts will lead toward more nuanced predictors of outcomes, including novel biomarkers, as part of the quest towards precision medicine.⁴³,⁴⁸

While notable efforts have been made to establish the disease prevalence in both adults and children,¹⁻³,⁴⁸ there are critical knowledge gaps in most countries and regions. The panel prioritised additional studies to better quantify the overall burden, including the disease prevalence and the quality of life impairment, in the general population and in high-risk groups (priority 1.1; ranked 2nd in its domain).

The panel almost universally agreed that additional studies are necessary to better quantify both the direct and indirect costs of fatty liver disease (priority 1.3). Available studies, while showing substantial costs associated with the disease,¹⁰,¹¹,⁴⁹,⁵⁰ are limited to a small number of high-income countries. Of equal importance to the panel was to advance understanding of the factors driving inequities in fatty liver disease (priority 1.5). The limited data in existence highlight large inequities by social group⁵¹ and mirror what is seen more widely with non-communicable diseases (NCDs).⁵² Further elucidating these factors will support the development of more targeted approaches to prevent and manage the burden of fatty liver disease.

## Advancing health system responses to fatty liver disease

### Defining and implementing multidisciplinary models of care

One of the greatest challenges in clinical practice remains the identification of those with fatty liver disease and subsequent risk-stratification of those needing aggressive intervention and close monitoring by a specialist, from those who can be managed in primary care. Great advances have been made on the use of NITs in the past decades⁴⁸,⁵³,⁵⁴ and there is increasingly robust evidence of the value of current NITs for prognostication,²⁰,²¹ yet substantial challenges remain.⁵⁵ There is a critical unmet need when it comes to non-invasive approaches for monitoring disease progression and assessing disease resolution or meaningful improvements in fibrosis.⁴⁸,⁵⁶,⁵⁷ The panel unanimously recognised this imperative and gave a high priority to further validating NITs, with a focus on enabling early diagnosis, prognosis, and monitoring of

liver disease progression (priority 2.4; ranked 1st in its domain). Within this, emphasis will be needed on the cost-effectiveness of different approaches within different resource environments¹⁹,⁵⁸,⁵⁹ and the appropriate cut-offs to be used in different settings and population groups.⁶⁰

The multisystem nature of fatty liver disease, and the fact that many patients present with a range of comorbidities, requires a multi-disciplinary approach to management and care;¹⁶,⁶¹,⁶² however, multi-disciplinary care models have not been widely adopted in most healthcare settings.¹⁶ The panel unanimously called for further studies to determine the effectiveness of different models of care, including the impact on patient outcomes and their cost-effectiveness (priority 2.1; ranked 2nd in its domain). As this work advances, emphasis should be placed on care models that can be adaptable and implementable based on local resources. Specific considerations are needed around care models for paediatric populations (priority 2.2).⁶³⁻⁶⁶

Alongside the development of effective care models, the heterogeneity of patient presentation, coupled with the large burden of disease, means that tools are needed to support clinicians to identify those at highest risk of disease progression and adverse outcomes. The panel stressed the need to validate risk prediction models in different population groups, enabling them to be tailored to specific groups (priority 2.3; ranked 3rd in its domain).

The use of digital technologies in healthcare settings holds great potential for supporting service delivery,⁶⁷ yet this is a relatively new area of research within the field of fatty liver disease.⁶⁸⁻⁷¹ The panel supported the exploration of how novel digital technologies can be utilised within healthcare settings (priority 2.5) and further exploration of the potential for artificial intelligence methods to improve diagnosis of fatty liver disease (priority 2.7). The panel also supported further understanding how digital health approaches can support patients to achieve lifestyle behavioural change (priority 2.6). This work can build upon and complement broader efforts within the NCD and mental health fields.⁷²,⁷³

### Accelerating advances in fatty liver disease treatment

In advancing treatment and care for affected populations, the panel highly ranked the importance of understanding the role of NITs in guiding treatment indication, response, and discontinuation, as well as predicting outcomes (priority 3.2; ranked 1st in its domain). This priority speaks to the current gap in evidence on the use of NITs to gain information on therapeutic responses.⁴⁸,⁷⁴ As specific therapeutics are approved, NITs which can guide treatment decisions will be critical, especially given the likely long duration and high cost of treatment.

Currently, the central focus of treatment for fatty liver disease has been lifestyle interventions (e.g., nutrition, exercise, and weight loss), pharmacological treatment of comorbidities such as obesity and diabetes, and liver-directed therapies. The panel acknowledged that the prevention of fatty liver disease-related cirrhosis or HCC will require multi-pronged strategies which address an array of risk factors (e.g., social, environmental, behavioural, biological, and genetic) and called for studies to assess the efficacy and cost-effectiveness of such strategies (priority 3.1; ranked 2nd in its domain). As fatty liver disease treatment options expand, patient-centred decision
<table><caption>Table 2. Consensus statements for a fatty liver disease research priorities agenda.</caption><thead><tr><th>Statement</th><th>Grade</th><th>Rank</th><th>A (%)</th><th>SA (%)</th><th>A+SA (%)</th><th>SD (%)</th><th>D (%)</th><th>NQ (%)</th><th>N</th></tr></thead><tbody><tr><td colspan="10"><strong>Domain 1: The human and economic burden</strong></td></tr><tr><td>1.1 Implement studies to better quantify the fatty liver disease burden, including health-related quality of life, in the general population and in specific high-risk groups.</td><td>A</td><td>2</td><td>92.7</td><td>6.3</td><td>99.0</td><td>0.7</td><td>0.3</td><td>0.0</td><td>288</td></tr><tr><td>1.2 Conduct cohort studies to prospectively monitor outcomes in patients with defined liver disease phenotypes (e.g., NASH, NASH with fibrosis, cirrhosis, hepatocellular carcinoma).</td><td>U</td><td>1</td><td>93.0</td><td>6.6</td><td>99.7</td><td>0.3</td><td>0.0</td><td>0.3</td><td>287</td></tr><tr><td>1.3 Conduct additional studies on the socioeconomic costs of fatty liver disease, capturing direct and indirect costs.</td><td>A</td><td></td><td>84.3</td><td>13.2</td><td>97.6</td><td>1.7</td><td>0.7</td><td>0.3</td><td>287</td></tr><tr><td>1.4 Develop and validate risk prediction models to forecast progressive hepatic and extrahepatic outcomes, to inform clinical decision making.</td><td>U</td><td>3</td><td>91.6</td><td>8.4</td><td>100.0</td><td>0.0</td><td>0.0</td><td>0.7</td><td>286</td></tr><tr><td>1.5 Report all data disaggregated by sex, race, ethnicity, age, socioeconomic status, education level, and other variables related to inequities.</td><td>A</td><td></td><td>74.2</td><td>23.3</td><td>97.6</td><td>2.1</td><td>0.3</td><td>0.3</td><td>287</td></tr><tr><td colspan="10"><strong>Domain 2: Defining and implementing models of care</strong></td></tr><tr><td>2.1 Determine the effectiveness of different models of care for fatty liver disease, including their impact on patient outcomes and their cost-effectiveness.</td><td>U</td><td>2</td><td>90.6</td><td>9.0</td><td>99.7</td><td>0.0</td><td>0.3</td><td>0.0</td><td>288</td></tr><tr><td>2.2 Validate multidisciplinary models of care for fatty liver disease in paediatric populations.</td><td>A</td><td></td><td>80.7</td><td>17.9</td><td>98.6</td><td>1.4</td><td>0.0</td><td>2.8</td><td>280</td></tr><tr><td>2.3 Evaluate how risk prediction models for fatty liver disease perform in different populations, so that they can be tailored to specific populations and groups.</td><td>A</td><td>3</td><td>85.1</td><td>12.8</td><td>97.9</td><td>1.7</td><td>0.3</td><td>0.0</td><td>288</td></tr><tr><td>2.4 Validate non-invasive tests to enable early diagnosis, prognosis, and monitoring of liver disease progression.</td><td>U</td><td>1</td><td>93.4</td><td>6.3</td><td>99.7</td><td>0.3</td><td>0.0</td><td>0.0</td><td>288</td></tr><tr><td>2.5 Explore how novel digital technologies (e.g., artificial intelligence, data-based analytics, digital health applications and therapeutics) can be utilised within healthcare settings.</td><td>A</td><td></td><td>73.2</td><td>21.3</td><td>94.4</td><td>4.9</td><td>0.7</td><td>0.3</td><td>287</td></tr><tr><td>2.6 Assess how digital health (e.g., applications, interventions, therapeutics) can support patients to achieve lifestyle behavioural change.</td><td>A</td><td></td><td>69.8</td><td>26.7</td><td>96.5</td><td>2.8</td><td>0.7</td><td>0.0</td><td>288</td></tr><tr><td>2.7 Further explore the use of artificial intelligence to improve diagnostics for fatty liver disease.</td><td>A</td><td></td><td>63.9</td><td>31.2</td><td>95.1</td><td>3.5</td><td>1.4</td><td>1.0</td><td>285</td></tr><tr><td colspan="10"><strong>Domain 3: Treatment and care</strong></td></tr><tr><td>3.1 Assess the efficacy and cost-effectiveness of multi-faceted strategies (e.g., social, environmental, behavioural, biological) to prevent fatty liver-related cirrhosis and hepatocellular carcinoma.</td><td>A</td><td>2</td><td>84.7</td><td>14.3</td><td>99.0</td><td>0.7</td><td>0.3</td><td>0.3</td><td>287</td></tr><tr><td>3.2 Study the role of non-invasive tests in guiding treatment indication, response, and discontinuation, as well as predicting outcomes.</td><td>A</td><td>1</td><td>94.1</td><td>5.2</td><td>99.3</td><td>0.3</td><td>0.3</td><td>0.0</td><td>288</td></tr><tr><td>3.3 Evaluate patient-centred decision making in relation to fatty liver disease treatment and care outcomes.</td><td>A</td><td></td><td>79.5</td><td>16.3</td><td>95.8</td><td>3.5</td><td>0.7</td><td>0.0</td><td>288</td></tr><tr><td>3.4 Evaluate the efficacy and cost-effectiveness of the optimal management of related diseases (e.g., diabetes, obesity) on fatty liver disease and other liver-related outcomes.</td><td>U</td><td>3</td><td>90.3</td><td>9.4</td><td>99.7</td><td>0.3</td><td>0.0</td><td>0.0</td><td>288</td></tr><tr><td colspan="10"><strong>Domain 4: Education and awareness</strong></td></tr><tr><td>4.1 Conduct comparative population-based surveys to understand fatty liver disease knowledge amongst the general population and high-risk groups specifically, to inform the development of awareness-raising approaches.</td><td>A</td><td>2</td><td>82.2</td><td>14.6</td><td>96.9</td><td>2.1</td><td>1.0</td><td>0.3</td><td>287</td></tr></tbody></table>

(continued on next page)
<table><caption>Table 2. Consensus statements for a fatty liver disease research priorities agenda.</caption><thead><tr><th>Statement</th><th>Grade</th><th>Rank</th><th>A (%)</th><th>SA (%)</th><th>A+SA (%)</th><th>SD (%)</th><th>D (%)</th><th>NQ (%)</th><th>N</th></tr></thead><tbody><tr><td colspan="10"><strong>Domain 1: The human and economic burden</strong></td></tr><tr><td>1.1 Implement studies to better quantify the fatty liver disease burden, including health-related quality of life, in the general population and in specific high-risk groups.</td><td>A</td><td>2</td><td>92.7</td><td>6.3</td><td>99.0</td><td>0.7</td><td>0.3</td><td>0.0</td><td>288</td></tr><tr><td>1.2 Conduct cohort studies to prospectively monitor outcomes in patients with defined liver disease phenotypes (e.g., NASH, NASH with fibrosis, cirrhosis, hepatocellular carcinoma).</td><td>U</td><td>1</td><td>93.0</td><td>6.6</td><td>99.7</td><td>0.3</td><td>0.0</td><td>0.3</td><td>287</td></tr><tr><td>1.3 Conduct additional studies on the socioeconomic costs of fatty liver disease, capturing direct and indirect costs.</td><td>A</td><td></td><td>84.3</td><td>13.2</td><td>97.6</td><td>1.7</td><td>0.7</td><td>0.3</td><td>287</td></tr><tr><td>1.4 Develop and validate risk prediction models to forecast progressive hepatic and extrahepatic outcomes, to inform clinical decision making.</td><td>U</td><td>3</td><td>91.6</td><td>8.4</td><td>100.0</td><td>0.0</td><td>0.0</td><td>0.7</td><td>286</td></tr><tr><td>1.5 Report all data disaggregated by sex, race, ethnicity, age, socioeconomic status, education level, and other variables related to inequities.</td><td>A</td><td></td><td>74.2</td><td>23.3</td><td>97.6</td><td>2.1</td><td>0.3</td><td>0.3</td><td>287</td></tr><tr><td colspan="10"><strong>Domain 2: Defining and implementing models of care</strong></td></tr><tr><td>2.1 Determine the effectiveness of different models of care for fatty liver disease, including their impact on patient outcomes and their cost-effectiveness.</td><td>U</td><td>2</td><td>90.6</td><td>9.0</td><td>99.7</td><td>0.0</td><td>0.3</td><td>0.0</td><td>288</td></tr><tr><td>2.2 Validate multidisciplinary models of care for fatty liver disease in paediatric populations.</td><td>A</td><td></td><td>80.7</td><td>17.9</td><td>98.6</td><td>1.4</td><td>0.0</td><td>2.8</td><td>280</td></tr><tr><td>2.3 Evaluate how risk prediction models for fatty liver disease perform in different populations, so that they can be tailored to specific populations and groups.</td><td>A</td><td>3</td><td>85.1</td><td>12.8</td><td>97.9</td><td>1.7</td><td>0.3</td><td>0.0</td><td>288</td></tr><tr><td>2.4 Validate non-invasive tests to enable early diagnosis, prognosis, and monitoring of liver disease progression.</td><td>U</td><td>1</td><td>93.4</td><td>6.3</td><td>99.7</td><td>0.3</td><td>0.0</td><td>0.0</td><td>288</td></tr><tr><td>2.5 Explore how novel digital technologies (e.g., artificial intelligence, data-based analytics, digital health applications and therapeutics) can be utilised within healthcare settings.</td><td>A</td><td></td><td>73.2</td><td>21.3</td><td>94.4</td><td>4.9</td><td>0.7</td><td>0.3</td><td>287</td></tr><tr><td>2.6 Assess how digital health (e.g., applications, interventions, therapeutics) can support patients to achieve lifestyle behavioural change.</td><td>A</td><td></td><td>69.8</td><td>26.7</td><td>96.5</td><td>2.8</td><td>0.7</td><td>0.0</td><td>288</td></tr><tr><td>2.7 Further explore the use of artificial intelligence to improve diagnostics for fatty liver disease.</td><td>A</td><td></td><td>63.9</td><td>31.2</td><td>95.1</td><td>3.5</td><td>1.4</td><td>1.0</td><td>285</td></tr><tr><td colspan="10"><strong>Domain 3: Treatment and care</strong></td></tr><tr><td>3.1 Assess the efficacy and cost-effectiveness of multi-faceted strategies (e.g., social, environmental, behavioural, biological) to prevent fatty liver-related cirrhosis and hepatocellular carcinoma.</td><td>A</td><td>2</td><td>84.7</td><td>14.3</td><td>99.0</td><td>0.7</td><td>0.3</td><td>0.3</td><td>287</td></tr><tr><td>3.2 Study the role of non-invasive tests in guiding treatment indication, response, and discontinuation, as well as predicting outcomes.</td><td>A</td><td>1</td><td>94.1</td><td>5.2</td><td>99.3</td><td>0.3</td><td>0.3</td><td>0.0</td><td>288</td></tr><tr><td>3.3 Evaluate patient-centred decision making in relation to fatty liver disease treatment and care outcomes.</td><td>A</td><td></td><td>79.5</td><td>16.3</td><td>95.8</td><td>3.5</td><td>0.7</td><td>0.0</td><td>288</td></tr><tr><td>3.4 Evaluate the efficacy and cost-effectiveness of the optimal management of related diseases (e.g., diabetes, obesity) on fatty liver disease and other liver-related outcomes.</td><td>U</td><td>3</td><td>90.3</td><td>9.4</td><td>99.7</td><td>0.3</td><td>0.0</td><td>0.0</td><td>288</td></tr><tr><td colspan="10"><strong>Domain 4: Education and awareness</strong></td></tr><tr><td>4.1 Conduct comparative population-based surveys to understand fatty liver disease knowledge amongst the general population and high-risk groups specifically, to inform the development of awareness-raising approaches.</td><td>A</td><td>2</td><td>82.2</td><td>14.6</td><td>96.9</td><td>2.1</td><td>1.0</td><td>0.3</td><td>287</td></tr></tbody></table>

(continued on next page)
Global research priority agenda for fatty liver disease

<table><caption>**Table 2. (continued)**</caption><thead><tr><th>Statement</th><th>Grade</th><th>Rank</th><th>A (%)</th><th>SA (%)</th><th>A+SA (%)</th><th>SD (%)</th><th>D (%)</th><th>NQ (%)</th><th>N</th></tr></thead><tbody><tr><td>4.2 Conduct research to identify the educational needs of healthcare providers in key areas, such as primary care, diabetes/endocrinology, obesity medicine, and cardiology, about fatty liver disease.</td><td>A</td><td>1</td><td>89.6</td><td>9.4</td><td>99.0</td><td>0.7</td><td>0.3</td><td>0.0</td><td>288</td></tr><tr><td>4.3 Study the effectiveness of strategies to impact fatty liver disease knowledge, attitudes, beliefs, and practices (KABPs), prioritising KABPs among healthcare professionals and high-risk groups.</td><td>A</td><td>3</td><td>72.8</td><td>25.4</td><td>98.3</td><td>1.0</td><td>0.7</td><td>0.3</td><td>287</td></tr><tr><td colspan="10"><strong>Domain 5: Patient and community perspectives</strong></td></tr><tr><td>5.1 Conduct research to understand the needs and experiences of fatty liver disease patients and at-risk communities (e.g., perspectives around prevention, treatment, and care, including mental health).</td><td>A</td><td>2</td><td>78.0</td><td>19.2</td><td>97.2</td><td>2.4</td><td>0.3</td><td>0.3</td><td>287</td></tr><tr><td>5.2 Study the impact of treatment and care on overall quality of life, including functional status (physical, psychological, social), in fatty liver disease patients.</td><td>A</td><td>1</td><td>81.9</td><td>17.4</td><td>99.3</td><td>0.7</td><td>0.0</td><td>0.0</td><td>288</td></tr><tr><td>5.3 Assess if published patient guidelines result in patients having an improved understanding of fatty liver disease and taking a more active role in their disease management.</td><td>A</td><td></td><td>71.9</td><td>25.7</td><td>97.6</td><td>2.1</td><td>0.3</td><td>0.0</td><td>288</td></tr><tr><td>5.4 Evaluate the efficacy of patient-led self-care programmes in improving fatty liver disease outcomes.</td><td>A</td><td></td><td>74.6</td><td>22.0</td><td>96.5</td><td>3.5</td><td>0.0</td><td>0.3</td><td>287</td></tr><tr><td>5.5 Explore the potential of new technologies (e.g., digital health applications and therapeutics, mobile interventions) to foster patient engagement in treatment and care.</td><td>A</td><td>3</td><td>75.5</td><td>21.3</td><td>96.9</td><td>2.4</td><td>0.7</td><td>0.7</td><td>286</td></tr><tr><td>5.6 Evaluate the effect of interventions to reduce liver disease stigma among patients, the public, and healthcare providers.</td><td>A</td><td></td><td>74.7</td><td>21.2</td><td>95.8</td><td>2.8</td><td>1.4</td><td>0.0</td><td>288</td></tr><tr><td colspan="10"><strong>Domain 6: Leadership and policies for the fatty liver disease public health agenda</strong></td></tr><tr><td>6.1 Conduct periodic studies of national and sub-national policies and guidelines for the prevention and management of fatty liver disease, to identify trends and gaps, and assess their implementation.</td><td>A</td><td>1</td><td>79.4</td><td>18.8</td><td>98.3</td><td>1.0</td><td>0.7</td><td>0.3</td><td>287</td></tr><tr><td>6.2 Analyse policy successes and failures in addressing non-communicable diseases, to inform the development of fatty liver disease-specific strategies.</td><td>A</td><td>2</td><td>82.6</td><td>14.6</td><td>97.2</td><td>2.4</td><td>0.3</td><td>0.3</td><td>287</td></tr><tr><td>6.3 Monitor, study, and report mentions of fatty liver disease within patient groups and professional societies outside of the field of hepatology (e.g., at events, in publications).</td><td>A</td><td>3</td><td>66.8</td><td>28.0</td><td>94.8</td><td>3.8</td><td>1.4</td><td>0.7</td><td>286</td></tr><tr><td><strong>Mean % agreement</strong></td><td></td><td></td><td>81.1</td><td>16.6</td><td>97.7</td><td></td><td></td><td></td><td></td></tr></tbody></table>

Percentages may add up to >100 due to rounding. Grades are based on the percentage of combined agreement ('agree' + 'somewhat agree'). U, unanimous (100%) agreement; A, 90-99% agreement. Responses to each statement are presented as percentages of the total responses. A, agree; SA, somewhat agree; SD, somewhat disagree; D, disagree; NQ, the percentage of participants that indicated that they were not qualified to respond; N, total number of responses; NASH, non-alcoholic steatohepatitis.

making will also become increasingly important (priority 3.3), as seen more broadly in the NCD field.⁷⁵,⁷⁶

Recognising the shared metabolic risks inherent in both fatty liver disease and other highly prevalent co-morbidities, the panel unanimously highlighted the importance of further evaluating the efficacy and cost-effectiveness of optimal management of related diseases (e.g., diabetes and obesity) on liver-related outcomes (priority 3.4; ranked 3rd in its domain). These factors increase risk of fibrosis progression, which in turn increases all-cause mortality, with the majority of patients succumbing to cardiovascular disease and solid organ malignancy,⁴⁶,⁷⁷ but further evidence is needed that optimal management of these comorbidities has a beneficial impact on

hepatic outcomes.⁷⁸ This evidence will be critical in ongoing efforts to engage and involve primary care and non-liver specialities within the multidisciplinary management of fatty liver disease.

### Improving knowledge and awareness

Despite fatty liver disease being highly prevalent, awareness is generally low amongst non-liver health specialists – most importantly primary care physicians and diabetologists – with critical knowledge gaps around risk-factors, diagnosis, and management approaches⁷⁹⁻⁸¹ and a lack of tools to support clinical decision making.⁷⁹ While important progress is being made in this area,⁸² the panel gave prominence to research
# Global research priority agenda for fatty liver disease

<table><caption>**Table 2. (continued)**</caption><thead><tr><th>Statement</th><th>Grade</th><th>Rank</th><th>A (%)</th><th>SA (%)</th><th>A+SA (%)</th><th>SD (%)</th><th>D (%)</th><th>NQ (%)</th><th>N</th></tr></thead><tbody><tr><td>4.2 Conduct research to identify the educational needs of healthcare providers in key areas, such as primary care, diabetes/endocrinology, obesity medicine, and cardiology, about fatty liver disease.</td><td>A</td><td>1</td><td>89.6</td><td>9.4</td><td>99.0</td><td>0.7</td><td>0.3</td><td>0.0</td><td>288</td></tr><tr><td>4.3 Study the effectiveness of strategies to impact fatty liver disease knowledge, attitudes, beliefs, and practices (KABPs), prioritising KABPs among healthcare professionals and high-risk groups.</td><td>A</td><td>3</td><td>72.8</td><td>25.4</td><td>98.3</td><td>1.0</td><td>0.7</td><td>0.3</td><td>287</td></tr><tr><td colspan="10"><strong>Domain 5: Patient and community perspectives</strong></td></tr><tr><td>5.1 Conduct research to understand the needs and experiences of fatty liver disease patients and at-risk communities (e.g., perspectives around prevention, treatment, and care, including mental health).</td><td>A</td><td>2</td><td>78.0</td><td>19.2</td><td>97.2</td><td>2.4</td><td>0.3</td><td>0.3</td><td>287</td></tr><tr><td>5.2 Study the impact of treatment and care on overall quality of life, including functional status (physical, psychological, social), in fatty liver disease patients.</td><td>A</td><td>1</td><td>81.9</td><td>17.4</td><td>99.3</td><td>0.7</td><td>0.0</td><td>0.0</td><td>288</td></tr><tr><td>5.3 Assess if published patient guidelines result in patients having an improved understanding of fatty liver disease and taking a more active role in their disease management.</td><td>A</td><td></td><td>71.9</td><td>25.7</td><td>97.6</td><td>2.1</td><td>0.3</td><td>0.0</td><td>288</td></tr><tr><td>5.4 Evaluate the efficacy of patient-led self-care programmes in improving fatty liver disease outcomes.</td><td>A</td><td></td><td>74.6</td><td>22.0</td><td>96.5</td><td>3.5</td><td>0.0</td><td>0.3</td><td>287</td></tr><tr><td>5.5 Explore the potential of new technologies (e.g., digital health applications and therapeutics, mobile interventions) to foster patient engagement in treatment and care.</td><td>A</td><td>3</td><td>75.5</td><td>21.3</td><td>96.9</td><td>2.4</td><td>0.7</td><td>0.7</td><td>286</td></tr><tr><td>5.6 Evaluate the effect of interventions to reduce liver disease stigma among patients, the public, and healthcare providers.</td><td>A</td><td></td><td>74.7</td><td>21.2</td><td>95.8</td><td>2.8</td><td>1.4</td><td>0.0</td><td>288</td></tr><tr><td colspan="10"><strong>Domain 6: Leadership and policies for the fatty liver disease public health agenda</strong></td></tr><tr><td>6.1 Conduct periodic studies of national and sub-national policies and guidelines for the prevention and management of fatty liver disease, to identify trends and gaps, and assess their implementation.</td><td>A</td><td>1</td><td>79.4</td><td>18.8</td><td>98.3</td><td>1.0</td><td>0.7</td><td>0.3</td><td>287</td></tr><tr><td>6.2 Analyse policy successes and failures in addressing non-communicable diseases, to inform the development of fatty liver disease-specific strategies.</td><td>A</td><td>2</td><td>82.6</td><td>14.6</td><td>97.2</td><td>2.4</td><td>0.3</td><td>0.3</td><td>287</td></tr><tr><td>6.3 Monitor, study, and report mentions of fatty liver disease within patient groups and professional societies outside of the field of hepatology (e.g., at events, in publications).</td><td>A</td><td>3</td><td>66.8</td><td>28.0</td><td>94.8</td><td>3.8</td><td>1.4</td><td>0.7</td><td>286</td></tr><tr><td><strong>Mean % agreement</strong></td><td></td><td></td><td>81.1</td><td>16.6</td><td>97.7</td><td></td><td></td><td></td><td></td></tr></tbody></table>

Percentages may add up to >100 due to rounding. Grades are based on the percentage of combined agreement ('agree' + 'somewhat agree'). U, unanimous (100%) agreement; A, 90-99% agreement. Responses to each statement are presented as percentages of the total responses. A, agree; SA, somewhat agree; SD, somewhat disagree; D, disagree; NQ, the percentage of participants that indicated that they were not qualified to respond; N, total number of responses; NASH, non-alcoholic steatohepatitis.

making will also become increasingly important (priority 3.3), as seen more broadly in the NCD field.⁷⁵,⁷⁶

Recognising the shared metabolic risks inherent in both fatty liver disease and other highly prevalent co-morbidities, the panel unanimously highlighted the importance of further evaluating the efficacy and cost-effectiveness of optimal management of related diseases (e.g., diabetes and obesity) on liver-related outcomes (priority 3.4; ranked 3rd in its domain). These factors increase risk of fibrosis progression, which in turn increases all-cause mortality, with the majority of patients succumbing to cardiovascular disease and solid organ malignancy,⁴⁶,⁷⁷ but further evidence is needed that optimal management of these comorbidities has a beneficial impact on

hepatic outcomes.⁷⁸ This evidence will be critical in ongoing efforts to engage and involve primary care and non-liver specialities within the multidisciplinary management of fatty liver disease.

## Improving knowledge and awareness

Despite fatty liver disease being highly prevalent, awareness is generally low amongst non-liver health specialists – most importantly primary care physicians and diabetologists – with critical knowledge gaps around risk-factors, diagnosis, and management approaches⁷⁹⁻⁸¹ and a lack of tools to support clinical decision making.⁷⁹ While important progress is being made in this area,⁸² the panel gave prominence to research
aimed at identifying the educational needs of healthcare providers in key areas, including primary care, diabetes, and obesity (priority 4.2; ranked 1st in its domain), to inform targeted educational strategies. Studies will also be needed to assess the effectiveness of such strategies to impact knowledge, attitudes/beliefs, and practices, starting with key healthcare professionals (priority 4.3; ranked 3rd in its domain).

Many people living with fatty liver disease are unaware of their fibrosis stage, which has important implications for adherence to management approaches.⁸³ Equally, within population groups at high risk of disease progression, including people with type 2 diabetes mellitus and other metabolic diseases, awareness of fatty liver disease, the health risks posed by it, or how it interacts with their other diseases, is low.⁸⁴,⁸⁵ To inform the development of awareness-raising approaches, the panel suggests that comparative population-based surveys are implemented to understand knowledge amongst the general population and high-risk groups (priority 4.1; ranked 2nd in its domain).

## Delivering whole-of-society responses

### Patient and community perspectives

The large prevalence of fatty liver disease and the less severe effects of steatosis potentially masks that, in advanced stages, the disease causes substantial impairment in quality of life which is often compounded in those with multiple morbidities.⁶⁻⁸ Alongside liver-related outcomes, fatigue and depression are important contributors to reduced quality of life in people living with fatty liver disease.⁸⁶,⁸⁷

While combined agreement on patient-centred orientations was high, the study's results noted above suggest that further discussion within the liver health community on research

priorities for patient and community engagement is warranted. The panel felt strongly about the need to study the impact of treatment and care on overall quality of life, including functional status (priority 5.2; ranked 1st in its domain). Knowledge gaps remain about patient needs and experiences,⁸⁸ including perspectives around prevention, treatment, and care. The panel prioritised studies that can advance this understanding (priority 5.1; ranked 2nd in its domain).

In chronic disease management, engaged patients are shown to have better outcomes,⁸⁹ while lower engagement levels are associated with more adverse events.⁹⁰ Digital approaches have proven effective at improving patient engagement in NCD management⁹¹,⁹² and initial efforts have been made to understand the role of technologies in fostering patient engagement in fatty liver disease treatment and care.⁹³,⁹⁴ The panel prioritised further exploration in this novel area of research (priority 5.5; ranked 3rd in its domain). In the area of patient engagement, the panel also agreed that assessing the impact of patient care guidelines⁹⁵ will be important (priority 5.3).

In other areas, the panel agreed on further evaluating the efficacy of patient-led self-care programmes in improving fatty liver disease outcomes (priority 5.4) and evaluating the effect of interventions to reduce liver disease stigma among patients, the public, and healthcare providers (priority 5.6).

## Leadership and public health policies

From the local to the global level, public health policy responses to fatty liver disease have, to date, not stemmed the increase in fatty liver disease morbidity or mortality.³¹,³⁴,⁹⁶ A global review of policies, strategies, and guidelines conducted in 2020 found that of 102 countries assessed, around one-third

<figure><img src="image_7.png" /><figcaption>Fig. 2. Research priorities agenda for fatty liver disease.</figcaption></figure>
aimed at identifying the educational needs of healthcare providers in key areas, including primary care, diabetes, and obesity (priority 4.2; ranked 1st in its domain), to inform targeted educational strategies. Studies will also be needed to assess the effectiveness of such strategies to impact knowledge, attitudes/beliefs, and practices, starting with key healthcare professionals (priority 4.3; ranked 3rd in its domain).

Many people living with fatty liver disease are unaware of their fibrosis stage, which has important implications for adherence to management approaches.⁸³ Equally, within population groups at high risk of disease progression, including people with type 2 diabetes mellitus and other metabolic diseases, awareness of fatty liver disease, the health risks posed by it, or how it interacts with their other diseases, is low.⁸⁴,⁸⁵ To inform the development of awareness-raising approaches, the panel suggests that comparative population-based surveys are implemented to understand knowledge amongst the general population and high-risk groups (priority 4.1; ranked 2nd in its domain).

## Delivering whole-of-society responses

### Patient and community perspectives

The large prevalence of fatty liver disease and the less severe effects of steatosis potentially masks that, in advanced stages, the disease causes substantial impairment in quality of life which is often compounded in those with multiple morbidities.⁶⁻⁸ Alongside liver-related outcomes, fatigue and depression are important contributors to reduced quality of life in people living with fatty liver disease.⁸⁶,⁸⁷

While combined agreement on patient-centred orientations was high, the study's results noted above suggest that further discussion within the liver health community on research

priorities for patient and community engagement is warranted. The panel felt strongly about the need to study the impact of treatment and care on overall quality of life, including functional status (priority 5.2; ranked 1st in its domain). Knowledge gaps remain about patient needs and experiences,⁸⁸ including perspectives around prevention, treatment, and care. The panel prioritised studies that can advance this understanding (priority 5.1; ranked 2nd in its domain).

In chronic disease management, engaged patients are shown to have better outcomes,⁸⁹ while lower engagement levels are associated with more adverse events.⁹⁰ Digital approaches have proven effective at improving patient engagement in NCD management⁹¹,⁹² and initial efforts have been made to understand the role of technologies in fostering patient engagement in fatty liver disease treatment and care.⁹³,⁹⁴ The panel prioritised further exploration in this novel area of research (priority 5.5; ranked 3rd in its domain). In the area of patient engagement, the panel also agreed that assessing the impact of patient care guidelines⁹⁵ will be important (priority 5.3).

In other areas, the panel agreed on further evaluating the efficacy of patient-led self-care programmes in improving fatty liver disease outcomes (priority 5.4) and evaluating the effect of interventions to reduce liver disease stigma among patients, the public, and healthcare providers (priority 5.6).

## Leadership and public health policies

From the local to the global level, public health policy responses to fatty liver disease have, to date, not stemmed the increase in fatty liver disease morbidity or mortality.³¹,³⁴,⁹⁶ A global review of policies, strategies, and guidelines conducted in 2020 found that of 102 countries assessed, around one-third

<figure><img src="image_6.png" /><figcaption>Fig. 2. Research priorities agenda for fatty liver disease.</figcaption></figure>
Global research priority agenda for fatty liver disease

of countries scored zero on an associated preparedness index.⁹⁶ Fatty liver disease is also absent in otherwise broad, global strategies and guidelines, including the World Health Organization's NCD strategies.⁹⁷,⁹⁸ Building on past efforts, the panel near unanimously called for periodic studies to assess national and sub-national policies and guidelines for the prevention and management of fatty liver disease, to identify trends and gaps and assess their implementation (priority 6.1; ranked 1st in its domain).

Agreement was also reached on the need to analyse policy successes and failures in addressing NCDs, to inform the development of fatty liver disease-specific strategies (priority 6.2; ranked 2nd in its domain). This will require a greater focus within the liver heath community on the commercial determinants driving the increasing burden of fatty liver disease.⁹⁹

The multidisciplinary and multi-sectoral nature of the public health responses to fatty liver disease require further engagement and collaboration with those outside of the field of hepatology. In an effort to guide and inform such engagements, and assess their impact, the panel recommends efforts to monitor, study, and report mentions of fatty liver disease within patient groups and professional societies (priority 6.3; ranked 3rd in its domain).

Study strengths and limitations

The major strength of this study is its novelty as the first global effort to propose a comprehensive research agenda for fatty liver disease utilising the rigorous Delphi consensus methodology. Additionally, within this methodology, the ability to illustrate degrees of agreement by breaking-out ‘agree’ and ‘somewhat agree’ responses may assist decision makers and researchers. We suggest that the breadth of issues covered, combined with the relatively focused priorities, makes the

outcome both aspirational and practical. While this process did not consider how to operationalise these research priorities, including the resource requirements to do so, the findings can guide the investment decisions of research funders.

The Delphi methodology used in this study is an effective approach in consensus building, yet building consensus is not without challenges. In this study we used purposive sampling to develop a core group. To mitigate the biases of purposive sampling, we used snowballing and targeted sampling to yield a panel of 344 people diverse in both expertise and geographical representation. We do, however, acknowledge that the characteristics of the final group (e.g., predominantly based in high-income countries and employed in the academic sector), will have been reflected within the agreement levels of the research priorities. For instance, the lower levels of agreement on the more patient centric and policy-oriented priorities likely reflects the smaller proportion of the panel working in patient/policy advocacy. While 10.5% (n = 36) of the panel reported some engagement in patient/policy advocacy, this was the primary area of work for only 4.7% (n = 16). Conducting the survey in the English language may have also influenced who accepted the invitation to contribute.

Conclusions

Delivering comprehensive health system and public health responses to fatty liver disease will require the global health community to re-envision the landscape, grow the fatty liver disease community of practice, and place greater emphasis on collective and collaborative thinking and action. This global multidisciplinary effort has, for the first time, developed a consensus fatty liver disease research agenda that can serve as the foundation for turning the tide on this silent public health threat.

Affiliations

<footnote n="1">¹Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, University of Barcelona, Barcelona, Spain; ²Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; ³CUNY Graduate School of Public Health and Health Policy (CUNY SPH), New York, NY, USA; ⁴European Association for the Study of the Liver (EASL), Geneva, Switzerland; ⁵Independent Consultant, Nottingham, UK; ⁶Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA; ⁷Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada; ⁸Department of Epidemiology and Biostatistics, Schulich School of Medicine, Western University, London, Ontario, Canada; ⁹Department of Gastroenterology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile; ¹⁰Aix Marseille Univ, Inserm, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale, ISSPAM, Marseille, France; ¹¹Houston Methodist Hospital, Houston Research Institute, Houston, TX, USA; ¹²Barts Liver Centre, Blizard Institute, Queen Mary University of London, London, UK; ¹³Fatty Liver Program, Arizona Liver Health, Phoenix, AZ, USA; ¹⁴King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia; ¹⁵Liver Unit, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; ¹⁶Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany; ¹⁷Division of Hepatology, University of Dundee, Dundee, Scotland, UK; ¹⁸Multivisceral Transplant Unit-Gastroenterology, Department of Surgery, Oncology and Gastroenterology at the Padua University Hospital, Padua, Italy; ¹⁹Department of Hepatology and Transplant, Hospital Médica Sur, Mexico City, Mexico; ²⁰Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; ²¹Asociación Latinoamericana para el Estudio del Higado (ALEH), Santiago, Chile; ²²Clinica Universitária de Gastrenterologia, Laboratório de Nutrição, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal; ²³Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, University of Florida, Gainesville, FL, USA; ²⁴Greek Patients Association, Athens, Greece; ²⁵Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India; ²⁶Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, Belgium; ²⁷InflaMed Centre of Excellence, Laboratory for Experimental Medicine and Paediatrics, Translational Sciences in Inflammation and Immunology, Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk, Belgium; ²⁸Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden; ²⁹CUNY Center for Systems and Community Design and NYU-CUNY Prevention Research Center, New York, NY, USA; ³⁰Kautz 5 gUG, Köln, Germany; ³¹Independent Researcher, Ponte de Lima, Portugal; ³²Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark; ³³University California Berkeley School of Public Health, Berkeley, CA, USA; ³⁴National Institute for Health Research Birmingham Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham, Birmingham, UK; ³⁵Department of Medicine, University of Chicago, Chicago, IL, USA; ³⁶Department of Community Health and Social Sciences, CUNY Graduate School of Public Health and Health Policy, New York, NY, USA; ³⁷Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India; ³⁸Hepatology and Clinical Research Units, Hospital Universitario Austral, Buenos Aires, Argentina; ³⁹Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; ⁴⁰UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK; ⁴¹Precision Medicine, Biological Resource Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; ⁴²Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy; ⁴³School of Public Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel; ⁴⁴Department of Gastroenterology, Tel Aviv Medical Centre, Tel Aviv, Israel; ⁴⁵Metabolic Liver Research Program, I. Department of Medicine, University Medical</footnote>
Global research priority agenda for fatty liver disease

of countries scored zero on an associated preparedness index.⁹⁶ Fatty liver disease is also absent in otherwise broad, global strategies and guidelines, including the World Health Organization's NCD strategies.⁹⁷,⁹⁸ Building on past efforts, the panel near unanimously called for periodic studies to assess national and sub-national policies and guidelines for the prevention and management of fatty liver disease, to identify trends and gaps and assess their implementation (priority 6.1; ranked 1st in its domain).

Agreement was also reached on the need to analyse policy successes and failures in addressing NCDs, to inform the development of fatty liver disease-specific strategies (priority 6.2; ranked 2nd in its domain). This will require a greater focus within the liver heath community on the commercial determinants driving the increasing burden of fatty liver disease.⁹⁹

The multidisciplinary and multi-sectoral nature of the public health responses to fatty liver disease require further engagement and collaboration with those outside of the field of hepatology. In an effort to guide and inform such engagements, and assess their impact, the panel recommends efforts to monitor, study, and report mentions of fatty liver disease within patient groups and professional societies (priority 6.3; ranked 3rd in its domain).

Study strengths and limitations

The major strength of this study is its novelty as the first global effort to propose a comprehensive research agenda for fatty liver disease utilising the rigorous Delphi consensus methodology. Additionally, within this methodology, the ability to illustrate degrees of agreement by breaking-out ‘agree’ and ‘somewhat agree’ responses may assist decision makers and researchers. We suggest that the breadth of issues covered, combined with the relatively focused priorities, makes the

outcome both aspirational and practical. While this process did not consider how to operationalise these research priorities, including the resource requirements to do so, the findings can guide the investment decisions of research funders.

The Delphi methodology used in this study is an effective approach in consensus building, yet building consensus is not without challenges. In this study we used purposive sampling to develop a core group. To mitigate the biases of purposive sampling, we used snowballing and targeted sampling to yield a panel of 344 people diverse in both expertise and geographical representation. We do, however, acknowledge that the characteristics of the final group (e.g., predominantly based in high-income countries and employed in the academic sector), will have been reflected within the agreement levels of the research priorities. For instance, the lower levels of agreement on the more patient centric and policy-oriented priorities likely reflects the smaller proportion of the panel working in patient/policy advocacy. While 10.5% (n = 36) of the panel reported some engagement in patient/policy advocacy, this was the primary area of work for only 4.7% (n = 16). Conducting the survey in the English language may have also influenced who accepted the invitation to contribute.

Conclusions

Delivering comprehensive health system and public health responses to fatty liver disease will require the global health community to re-envision the landscape, grow the fatty liver disease community of practice, and place greater emphasis on collective and collaborative thinking and action. This global multidisciplinary effort has, for the first time, developed a consensus fatty liver disease research agenda that can serve as the foundation for turning the tide on this silent public health threat.

Affiliations

<footnote n="1">¹Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, University of Barcelona, Barcelona, Spain; ²Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; ³CUNY Graduate School of Public Health and Health Policy (CUNY SPH), New York, NY, USA; ⁴European Association for the Study of the Liver (EASL), Geneva, Switzerland; ⁵Independent Consultant, Nottingham, UK; ⁶Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA; ⁷Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada; ⁸Department of Epidemiology and Biostatistics, Schulich School of Medicine, Western University, London, Ontario, Canada; ⁹Department of Gastroenterology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile; ¹⁰Aix Marseille Univ, Inserm, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale, ISSPAM, Marseille, France; ¹¹Houston Methodist Hospital, Houston Research Institute, Houston, TX, USA; ¹²Barts Liver Centre, Blizard Institute, Queen Mary University of London, London, UK; ¹³Fatty Liver Program, Arizona Liver Health, Phoenix, AZ, USA; ¹⁴King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia; ¹⁵Liver Unit, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; ¹⁶Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany; ¹⁷Division of Hepatology, University of Dundee, Dundee, Scotland, UK; ¹⁸Multivisceral Transplant Unit-Gastroenterology, Department of Surgery, Oncology and Gastroenterology at the Padua University Hospital, Padua, Italy; ¹⁹Department of Hepatology and Transplant, Hospital Médica Sur, Mexico City, Mexico; ²⁰Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; ²¹Asociación Latinoamericana para el Estudio del Higado (ALEH), Santiago, Chile; ²²Clinica Universitária de Gastrenterologia, Laboratório de Nutrição, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal; ²³Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, University of Florida, Gainesville, FL, USA; ²⁴Greek Patients Association, Athens, Greece; ²⁵Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India; ²⁶Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, Belgium; ²⁷InflaMed Centre of Excellence, Laboratory for Experimental Medicine and Paediatrics, Translational Sciences in Inflammation and Immunology, Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk, Belgium; ²⁸Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden; ²⁹CUNY Center for Systems and Community Design and NYU-CUNY Prevention Research Center, New York, NY, USA; ³⁰Kautz 5 gUG, Köln, Germany; ³¹Independent Researcher, Ponte de Lima, Portugal; ³²Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark; ³³University California Berkeley School of Public Health, Berkeley, CA, USA; ³⁴National Institute for Health Research Birmingham Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham, Birmingham, UK; ³⁵Department of Medicine, University of Chicago, Chicago, IL, USA; ³⁶Department of Community Health and Social Sciences, CUNY Graduate School of Public Health and Health Policy, New York, NY, USA; ³⁷Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India; ³⁸Hepatology and Clinical Research Units, Hospital Universitario Austral, Buenos Aires, Argentina; ³⁹Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; ⁴⁰UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK; ⁴¹Precision Medicine, Biological Resource Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; ⁴²Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy; ⁴³School of Public Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel; ⁴⁴Department of Gastroenterology, Tel Aviv Medical Centre, Tel Aviv, Israel; ⁴⁵Metabolic Liver Research Program, I. Department of Medicine, University Medical</footnote>
Centre Mainz, Mainz, Germany; ⁴⁶The Chinese University of Hong Kong, Hong Kong; ⁴⁷Center for Liver Disease, Inova, Falls Church, VA, USA

## Abbreviations

HCC, hepatocellular carcinoma; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; NCD, non-communicable disease; NIT, non-invasive test; R, round.

## Financial support

The data collection and analysis were funded by the European Association for the Study of the Liver (EASL), with support from Takeda, MSD, Bristol-Myers-Squibb Company, and Apollo Endo.

## Conflict of interest

J.V.L. acknowledges grants and speaker fees from AbbVie, Gilead Sciences, MSD, and Roche Diagnostics to his institution, speaker fees from Intercept, Janssen, Novo Nordisk, and ViIV, and consulting fees from Novavax, outside of the submitted work. He also acknowledges support to ISGlobal from the grant CEX2018-000806-S funded by MCIN/AEI/10.13039/501100011033 and the Generalitat de Catalunya through the CERCA Programme, outside of the submitted work. H.E.M acknowledges consultancy fees from the European Association for the Study of The Liver (EASL) related to the current manuscript. A.M.A. acknowledges grant support to her institution from the National Institutes of Health (NIH) (DK128127), Novo Nordisk, Pfizer, and Target Pharma and advisory board participation for Novo Nordisk, outside of the submitted work. M.N. acknowledges consulting fees from and advisory board participation for Altimmune, BI, BMS, Cytodyn, 89BIO, EchoSens, Gilead, GSK, Madrigal, Merck, Novo Nordisk, OWL, Prespectum, Pfizer, Roche Diagnostics, Siemens, Terns, and Takeda, payment or honoraria from Madrigal, Echosens, and Sonic Incytes, patents from AI in NAFLD, roles as AASLD Vice-chair of NAFLD SIG and AE at CGH, and stock from Anaetos Rivus Pharma, CIMA, ChronWell, and Viking, outside of the submitted work. W.A. has received fees for consulting and teaching or competitively awarded grant funding from Gilead Sciences, GlaxoSmithKline, and AstraZeneca, outside of the submitted work. N.A. acknowledges grants or contracts from 89Bio, AbbVie/Allergan, Akero, Better Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Corcept, DSM, Galectin, Genentech, Genfit, Gilead, Hepagene, Heallo, Intercept, Inventiva, Ionis, Madrigal, Merck, NGM, Noom, NorthSea, Novo Nordisk, Perspectum, Pfizer, Poxel, Viking, and Zydus, consulting fees from AbbVie/Allergan, Echosens, Fibronostics, Gilead, Intercept, Madrigal, Novo Nordisk, Perspectum, Pfizer, and Zydus, and payment or honoraria from AbbVie/Allergan, Alexion, Echosens, Eisai, Exelixis, Gilead, Intercept, Perspectum, Salix, and Theratechnologies, outside of the submitted work. R.B. acknowledges payment or honoraria and support for attending meetings and/or travel from AbbVie, outside of the submitted work. T.B. acknowledges grants to or contracts with his institution from AbbVie, BMS, Gilead, MSD/Merck, Humedics, Intercept, Merz, Norgine, Novartis, Orphanal, and Sequana Medical, consulting fees from AbbVie, Alexion, Bayer, Gilead, GSK, Eisai, Enyo Pharma, HepaRegenX GmbH, Humedics, Intercept, Ipsen, Janssen, MSD/Merck, Novartis, Orphanal, Roche, Sequana Medical, SIRTEX, SOBI, and Shionogi, payment or honoraria from AbbVie, Alexion, Bayer, Gilead, Eisai, Falk Foundation, Intercept, Ipsen, Janssen, MedUpdate GmbH, MSD/Merck, Novartis, Orphanal, Sequana Medica, SIRTEX, and SOBI, and support for attending meetings and/or travel from Gilead, AbbVie, Intercept, and Janssen, outside of the submitted work. P.N.B. acknowledges consulting fees from Resolution Therapeutics and payment or honoraria from Takeda, outside of the submitted work. P.B. acknowledges payment or honoraria from Gilead and Chiesi Farmaceutici, support for attending meetings and/or travel from Alpha Wasserman, advisory board participation for Biotest, Kedrion, Astellas, Gilead, Sandoz, and Chiesi Farmaceutici, and a preceptorship for Novartis, outside of the submitted work. H.C-P acknowledges consulting fees from Orphanal and Novo Nordisk and lecture fees from and advisory board participation for Roche Portugal and EISAI, outside of the submitted work. K.C. acknowledges grant support to his institution from Echosens, Inventiva, Poxel, Novo, Labcorp, and Zydus, consulting fees from BMS, Lilly, Madrigal, Merck, Myovant, Novo Nordisk, Prosciento, Quest, Sagimet, Sonic Incytes, and Terns, and other support from Echosens, Inventiva, Poxel, Labcorp, and Zydus, outside of the submitted work. N.D. acknowledges roles as Chair of the Greek Patients Association and the Positive Voice (PLHIV Association), outside of the submitted work. A.D. acknowledges an unpaid role as Secretary-General of the Indian National Association for the Study of the Liver (INASL), outside of the submitted work. S.M.F. acknowledges grants or contracts from Research Foundation Flanders, Astellas, Falk Pharma, Genfit, Gilead Sciences, GlympsBio, Janssens Pharmaceutica, Inventiva, Merck Sharp & Dome, Pfizer, and Roche, consulting fees from AbbVie, Actelion, Aelin Therapeutics, Aligos Therapeutics, Allergan, Astellas, Astra Zeneca, Bayer, Boehringer

Ingelheim, Bristol-Meyers Squibb, CSL Behring, Coherus, Echosens, Eisai, Enyo, Galapagos, Galmed, Genetech, Genfit, Gilead Sciences, Intercept, Inventiva, Janssens Pharmaceutical, Julius Clinical, Madrigal, Medimmune, Merck Sharp & Dome, NGM Bio, Novartis, Novo Nordisk, Promethera, and Roche, and lecture fees from AbbVie, Allergan, Bayer, Eisai, Genfit, Gilead Sciences, Janssens Cilag, Intercept, Inventiva, Merck Sharp & Dome, Novo Nordisk, and Promethera, outside of the submitted work. H.H. acknowledges grants or contracts from Astra Zeneca, Pfizer, MSD, EchoSens, and Gilead, consulting fees from Astra Zeneca, and payment or honoraria from MediPlast, outside of the submitted work. T.T-K.H. acknowledges grants or contracts from the Centers for Disease Control and Prevention, outside of the submitted work. A.I.K. acknowledges grants or contracts from EU Horizon 20, the Novo Nordisk Foundation, Innovation Fund Denmark, the Danish National Research Foundation, the Region of Southern Denmark, and AstraZeneca, royalties or licenses from Gyldendal, payment or honoraria from Norgine, Siemens, and Nordic Bioscience, patents from the Region of Southern Denmark and the University of Southern Denmark, advisory board participation for Norgine and Siemens, an unpaid role as Vice Secretary of the European Association for the Study of The Liver (EASL), and other support from Norgine, Siemens, Echosence, and Nordic Bioscience, outside of the submitted work. V.M. acknowledges grants from 89Bio, Akero Therapeutics Inc., Albireo Pharma Inc., Aligos Therapeutics, Alimentiv, AlloVir, Altimmune Inc., AMRA Medical AB, Arrowhead Pharmaceuticals, ChemomAb Ltd., Covance Inc., Cymabay Therapeutics, E-Scopics, EA Pharma Co. LTD, Echosens, Eli Lilly & Company, ENYO Pharma SA, Galectin Therapeutics, Gilead Sciences Inc., GlaxoSmithKline PLC, HepQuant, High Tide Therapeutics, HistolIndex, Intercept Pharmaceuticals, Inventiva Pharma, Janssen, LabCorp, LG Chem Life Sciences, Merck & Company Inc., Northsea Therapeutics, Novartis Pharma AG, Novo Nordisk, Oncoustics, Pharmanest, Pliant Therapeutics, and Regeneron Pharmaceuticals to the Forum for Collaborative Research, outside of the submitted work. P.N.N. acknowledges grants or contracts from Novo Nordisk, consulting fees from Novo Nordisk, Boehringer Ingelheim, Gilead, Intercept, Poxel Pharmaceuticals, BMS, Pfizer, Sun Pharma, Madrigal, and GSK, payment or honoraria from Novo Nordisk and AiCME, support for attending meetings and/or travel from Novo Nordisk, and advisory board participation for Novo Nordisk, Boehringer Ingelheim, Gilead, Intercept, Poxel Pharmaceuticals, BMS, Pfizer, Sun Pharma, Madrigal, and GSK, outside of the submitted work. M.E.R. acknowledges consulting fees from Boehringer Ingelheim, Novo Nordisk, GSK, Intercept, Madrigal, and Cytodyn, outside of the submitted work. D.R. acknowledges remuneration to her institution from the European Association for the Study of The Liver (EASL) related to the current manuscript. M.S acknowledges grants to his institution from Inventiva, Zydus, and Merck, advisory board participation for Zydus, and unpaid leadership and membership roles for ALEH and the Global NASH Council, outside of the submitted work. C.W.S acknowledges payment or honoraria from Gilead Sciences and Abbott, support for attending meetings and/or travel from Gilead Sciences, and roles as Co-chair of the Society on Liver Disease of Africa and member of the International Advisory Board of *The Lancet Gastroenterology and Hepatology* journal, outside of the submitted work. E.A.T. acknowledges consulting fees from Novo Nordisk, Boehringer, and Pfizer, payment or honoraria from Novo Nordisk and Dr Falk, board participation for Boehringer, Pfizer, and Novo Nordisk, and a role a member of the EASL Governing Board, outside of the submitted work. L.V. acknowledges grants or contracts and support for attending meetings and/or travel from Gilead Sciences, consulting fees from Gilead, Pfizer, Astra Zeneca, Novo Nordisk, Intercept pharmaceuticals, Diatech Pharmacogenetics, IONIS, and Boehringer Ingelheim, payment or honoraria from MSD, Gilead, AlfaSigma, AbbVie, and Viatris, patents from Takeda, and board participation for Intercept, Pfizer, Gilead, Novo Nordisk, and Boehringer Ingelheim, outside of the submitted work. M.V-R acknowledges consultancy fees from the European Association for the Study of The Liver (EASL) related to the current manuscript. S.Z-S has given presentations for and received support for attending meetings and/or travel from AbbVie, outside of the submitted work. J.M.S acknowledges research funding from Gilead Sciences, Boehringer Ingelheim, and Siemens Healthcare GmbH, consulting fees from Apollo Endosurgery, Albireo Pharma Inc, Bayer, BMS, Boehringer Ingelheim, Gilead Sciences, GSK, Intercept Pharmaceuticals, Ipsen, Inventiva Pharma, Madrigal, MSD, Northsea Therapeutics, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi, and Siemens Healthcare GmbH, payment or honoraria from Boehringer Ingelheim, Echosens, MedPublico GmbH, Novo Nordisk, and Madrigal Pharmaceuticals, support for attending meetings and/or travel from Gilead Sciences, and stock from AGED diagnostics and Hepta Bio, outside of the submitted work. V.W-S.W acknowledges consultancy fees from Gilead Sciences to his institution, consulting fees from AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Intercept, Inventiva, Novo Nordisk, Pfizer, Sagimet Biosciences, and TARGET PharmaSolutions, payment and honoraria from Abbott,
Centre Mainz, Mainz, Germany; ⁴⁶The Chinese University of Hong Kong, Hong Kong; ⁴⁷Center for Liver Disease, Inova, Falls Church, VA, USA

## Abbreviations

HCC, hepatocellular carcinoma; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; NCD, non-communicable disease; NIT, non-invasive test; R, round.

## Financial support

The data collection and analysis were funded by the European Association for the Study of the Liver (EASL), with support from Takeda, MSD, Bristol-Myers-Squibb Company, and Apollo Endo.

## Conflict of interest

J.V.L. acknowledges grants and speaker fees from AbbVie, Gilead Sciences, MSD, and Roche Diagnostics to his institution, speaker fees from Intercept, Janssen, Novo Nordisk, and ViIV, and consulting fees from Novavax, outside of the submitted work. He also acknowledges support to ISGlobal from the grant CEX2018-000806-S funded by MCIN/AEI/10.13039/501100011033 and the Generalitat de Catalunya through the CERCA Programme, outside of the submitted work. H.E.M acknowledges consultancy fees from the European Association for the Study of The Liver (EASL) related to the current manuscript. A.M.A acknowledges grant support to her institution from the National Institutes of Health (NIH) (DK128127), Novo Nordisk, Pfizer, and Target Pharma and advisory board participation for Novo Nordisk, outside of the submitted work. M.N acknowledges consulting fees from and advisory board participation for Altimmune, BI, BMS, Cytodyn, 89BIO, EchoSens, Gilead, GSK, Madrigal, Merck, Novo Nordisk, OWL, Prespectum, Pfizer, Roche Diagnostics, Siemens, Terns, and Takeda, payment or honoraria from Madrigal, Echosens, and Sonic Incytes, patents from AI in NAFLD, roles as AASLD Vice-chair of NAFLD SIG and AE at CGH, and stock from Anaetos Rivus Pharma, CIMA, ChronWell, and Viking, outside of the submitted work. W.A has received fees for consulting and teaching or competitively awarded grant funding from Gilead Sciences, GlaxoSmithKline, and AstraZeneca, outside of the submitted work. N.A acknowledges grants or contracts from 89Bio, AbbVie/Allergan, Akero, Better Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Corcept, DSM, Galectin, Genentech, Genfit, Gilead, Hepagene, Heallo, Intercept, Inventiva, Ionis, Madrigal, Merck, NGM, Noom, NorthSea, Novo Nordisk, Perspectum, Pfizer, Poxel, Viking, and Zydus, consulting fees from AbbVie/Allergan, Echosens, Fibronostics, Gilead, Intercept, Madrigal, Novo Nordisk, Perspectum, Pfizer, and Zydus, and payment or honoraria from AbbVie/Allergan, Alexion, Echosens, Eisai, Exelixis, Gilead, Intercept, Perspectum, Salix, and Theratechnologies, outside of the submitted work. R.B acknowledges payment or honoraria and support for attending meetings and/or travel from AbbVie, outside of the submitted work. T.B acknowledges grants to or contracts with his institution from AbbVie, BMS, Gilead, MSD/Merck, Humedics, Intercept, Merz, Norgine, Novartis, Orphanal, and Sequana Medical, consulting fees from AbbVie, Alexion, Bayer, Gilead, GSK, Eisai, Enyo Pharma, HepaRegenX GmbH, Humedics, Intercept, Ipsen, Janssen, MSD/Merck, Novartis, Orphanal, Roche, Sequana Medical, SIRTEX, SOBI, and Shionogi, payment or honoraria from AbbVie, Alexion, Bayer, Gilead, Eisai, Falk Foundation, Intercept, Ipsen, Janssen, MedUpdate GmbH, MSD/Merck, Novartis, Orphanal, Sequana Medica, SIRTEX, and SOBI, and support for attending meetings and/or travel from Gilead, AbbVie, Intercept, and Janssen, outside of the submitted work. P.N.B acknowledges consulting fees from Resolution Therapeutics and payment or honoraria from Takeda, outside of the submitted work. P.B acknowledges payment or honoraria from Gilead and Chiesi Farmaceutici, support for attending meetings and/or travel from Alpha Wasserman, advisory board participation for Biotest, Kedrion, Astellas, Gilead, Sandoz, and Chiesi Farmaceutici, and a preceptorship for Novartis, outside of the submitted work. H.C-P acknowledges consulting fees from Orphanal and Novo Nordisk and lecture fees from and advisory board participation for Roche Portugal and EISAI, outside of the submitted work. K.C acknowledges grant support to his institution from Echosens, Inventiva, Poxel, Novo, Labcorp, and Zydus, consulting fees from BMS, Lilly, Madrigal, Merck, Myovant, Novo Nordisk, Prosciento, Quest, Sagimet, Sonic Incytes, and Terns, and other support from Echosens, Inventiva, Poxel, Labcorp, and Zydus, outside of the submitted work. N.D acknowledges roles as Chair of the Greek Patients Association and the Positive Voice (PLHIV Association), outside of the submitted work. A.D acknowledges an unpaid role as Secretary-General of the Indian National Association for the Study of the Liver (INASL), outside of the submitted work. S.M.F acknowledges grants or contracts from Research Foundation Flanders, Astellas, Falk Pharma, Genfit, Gilead Sciences, GlympsBio, Janssens Pharmaceutica, Inventiva, Merck Sharp & Dome, Pfizer, and Roche, consulting fees from AbbVie, Actelion, Aelin Therapeutics, Aligos Therapeutics, Allergan, Astellas, Astra Zeneca, Bayer, Boehringer

Ingelheim, Bristol-Meyers Squibb, CSL Behring, Coherus, Echosens, Eisai, Enyo, Galapagos, Galmed, Genetech, Genfit, Gilead Sciences, Intercept, Inventiva, Janssens Pharmaceutical, Julius Clinical, Madrigal, Medimmune, Merck Sharp & Dome, NGM Bio, Novartis, Novo Nordisk, Promethera, and Roche, and lecture fees from AbbVie, Allergan, Bayer, Eisai, Genfit, Gilead Sciences, Janssens Cilag, Intercept, Inventiva, Merck Sharp & Dome, Novo Nordisk, and Promethera, outside of the submitted work. H.H acknowledges grants or contracts from Astra Zeneca, Pfizer, MSD, EchoSens, and Gilead, consulting fees from Astra Zeneca, and payment or honoraria from MediPlast, outside of the submitted work. T.T-K.H acknowledges grants or contracts from the Centers for Disease Control and Prevention, outside of the submitted work. AI.K acknowledges grants or contracts from EU Horizon 20, the Novo Nordisk Foundation, Innovation Fund Denmark, the Danish National Research Foundation, the Region of Southern Denmark, and AstraZeneca, royalties or licenses from Gyldendal, payment or honoraria from Norgine, Siemens, and Nordic Bioscience, patents from the Region of Southern Denmark and the University of Southern Denmark, advisory board participation for Norgine and Siemens, an unpaid role as Vice Secretary of the European Association for the Study of The Liver (EASL), and other support from Norgine, Siemens, Echosence, and Nordic Bioscience, outside of the submitted work. V.M acknowledges grants from 89bio, Akero Therapeutics Inc., Albireo Pharma Inc., Aligos Therapeutics, Alimentiv, AlloVir, Altimmune Inc., AMRA Medical AB, Arrowhead Pharmaceuticals, ChemomAb Ltd., Covance Inc., Cymabay Therapeutics, E-Scopics, EA Pharma Co. LTD, Echosens, Eli Lilly & Company, ENYO Pharma SA, Galectin Therapeutics, Gilead Sciences Inc., GlaxoSmithKline PLC, HepQuant, High Tide Therapeutics, HistolIndex, Intercept Pharmaceuticals, Inventiva Pharma, Janssen, LabCorp, LG Chem Life Sciences, Merck & Company Inc., Northsea Therapeutics, Novartis Pharma AG, Novo Nordisk, Oncoustics, Pharmanest, Pliant Therapeutics, and Regeneron Pharmaceuticals to the Forum for Collaborative Research, outside of the submitted work. P.N.N acknowledges grants or contracts from Novo Nordisk, consulting fees from Novo Nordisk, Boehringer Ingelheim, Gilead, Intercept, Poxel Pharmaceuticals, BMS, Pfizer, Sun Pharma, Madrigal, and GSK, payment or honoraria from Novo Nordisk and AiCME, support for attending meetings and/or travel from Novo Nordisk, and advisory board participation for Novo Nordisk, Boehringer Ingelheim, Gilead, Intercept, Poxel Pharmaceuticals, BMS, Pfizer, Sun Pharma, Madrigal, and GSK, outside of the submitted work. M.E.R acknowledges consulting fees from Boehringer Ingelheim, Novo Nordisk, GSK, Intercept, Madrigal, and Cytodyn, outside of the submitted work. D.R. acknowledges remuneration to her institution from the European Association for the Study of The Liver (EASL) related to the current manuscript. M.S acknowledges grants to his institution from Inventiva, Zydus, and Merck, advisory board participation for Zydus, and unpaid leadership and membership roles for ALEH and the Global NASH Council, outside of the submitted work. C.W.S acknowledges payment or honoraria from Gilead Sciences and Abbott, support for attending meetings and/or travel from Gilead Sciences, and roles as Co-chair of the Society on Liver Disease of Africa and member of the International Advisory Board of *The Lancet Gastroenterology and Hepatology* journal, outside of the submitted work. E.A.T acknowledges consulting fees from Novo Nordisk, Boehringer, and Pfizer, payment or honoraria from Novo Nordisk and Dr Falk, board participation for Boehringer, Pfizer, and Novo Nordisk, and a role a member of the EASL Governing Board, outside of the submitted work. L.V acknowledges grants or contracts and support for attending meetings and/or travel from Gilead Sciences, consulting fees from Gilead, Pfizer, Astra Zeneca, Novo Nordisk, Intercept pharmaceuticals, Diatech Pharmacogenetics, IONIS, and Boehringer Ingelheim, payment or honoraria from MSD, Gilead, AlfaSigma, AbbVie, and Viatris, patents from Takeda, and board participation for Intercept, Pfizer, Gilead, Novo Nordisk, and Boehringer Ingelheim, outside of the submitted work. M.V-R acknowledges consultancy fees from the European Association for the Study of The Liver (EASL) related to the current manuscript. S.Z-S has given presentations for and received support for attending meetings and/or travel from AbbVie, outside of the submitted work. J.M.S acknowledges research funding from Gilead Sciences, Boehringer Ingelheim, and Siemens Healthcare GmbH, consulting fees from Apollo Endosurgery, Albireo Pharma Inc, Bayer, BMS, Boehringer Ingelheim, Gilead Sciences, GSK, Intercept Pharmaceuticals, Ipsen, Inventiva Pharma, Madrigal, MSD, Northsea Therapeutics, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi, and Siemens Healthcare GmbH, payment or honoraria from Boehringer Ingelheim, Echosens, MedPublico GmbH, Novo Nordisk, and Madrigal Pharmaceuticals, support for attending meetings and/or travel from Gilead Sciences, and stock from AGED diagnostics and Hepta Bio, outside of the submitted work. V.W-S.W acknowledges consultancy fees from Gilead Sciences to his institution, consulting fees from AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Intercept, Inventiva, Novo Nordisk, Pfizer, Sagimet Biosciences, and TARGET PharmaSolutions, payment and honoraria from Abbott,
## Global research priority agenda for fatty liver disease

AbbVie, Gilead Sciences, Novo Nordisk, and Unilab, support for attending meetings and/or travel from AbbVie and Gilead Sciences, and unpaid stock as co-founder of Illuminatio Medical Technology Limited, outside of the submitted work. Z.M.Y acknowledges consulting fees from Gilead, Intercept, Siemens, Novo Nordisk, Madrigal, Merck, Quest, and Bristol Myers Squibb, outside of the submitted work. J.P.A, P.C, S.A.A, M.A, G.C-N, D.I.W, A.K, C.J.K, and S.K.S have no conflicts of interest to disclose.

Please refer to the accompanying ICMJE disclosure forms for further details.

## Authors' contributions

This study was led by a core group of 40 co-authors. J.V.L led the core group and provided regular updates by email. Twenty-six core group members and 11 co-authors participated in a three-day in-person meeting hosted by Wilton Park, UK, in October 2022, which informed the development of the research priorities included in the Delphi study. Seven co-chairs (A.M.A, J.P.A, P.C, M.N, J.M.S, V.W-S.W, and Z.M.Y) led the drafting of seven evidence notes, including key priorities and challenges, ahead of the Wilton Park meeting and were supported by core group members (R.B, T.B, H.C-P, K.C, N.D, A.D, T.T-K.H, A.I.K, V.M, P.N.N, M.E.R, M.S, E.T, and S.Z-S). The evidence notes were reviewed by J.V.L and H.E.M and informed the drafting of the research priorities statements and actions. D.R and J.V.L led the methodology. J.V.L, H.E.M, P.N.B, C.J.K, D.R, D.I.W, and M.V-R reviewed comments submitted as part of the two survey rounds. J.V.L, H.E.M, and M.V-R reviewed all comments sent directly by email. All panel members provided two rounds of comments through Qualtrics XM. H.E.M, M.V-R, and J.V.L wrote the first draft of the manuscript, which was reviewed by the core group. Those fulfilling authorship criteria are named.

## Data availability statement

De-identified source data for all analyses will be made available by contacting the corresponding author (Jeffrey.Lazarus@sph.cuny.edu), with appropriate ethical approval and for fair use.

## Acknowledgments

The formation of the Healthy Livers, Healthy Lives global coalition builds on three years of work led initially by the EASL International Liver Foundation (EILF) and since 2021 by EASL. Collaboration has been at the centre of this work. Over 500 individuals and organisations spanning over 100 countries have engaged in these efforts, with multiple disciplines and sectors represented, including affected populations. As part of this process, in October 2022, delegates, including representatives from EASL, the American Association for the Study of Liver Diseases (AASLD), the Latin American Association for the Study of the Liver (Asociación Latinoamericana para el Estudio del Hígado [ALEH]) (representatives of the Asian Pacific Association for the Study of the Liver [APASL] were unable to attend), the Society on Liver Disease in Africa (SOLDA), the European Association for the Study of Diabetes (EASD), the European Association for the Study of Obesity (EASO), the European Society of Primary Care Gastroenterology (ESPCG), the Global NASH Council (GNC), United European Gastroenterology (UEG), the World Obesity Federation (WOF), and the World Organization of Family Doctors (WONCA), gathered for three days of discussion at Wilton Park, a UK-based forum for strategic dialogue.

We are grateful to the following experts for their contributions to the Delphi process: Manal F. Abdelmalek, Abdelmounem E. Abdo, Matthew J. Armstrong, Carol L. Brosgart, José Luis Calleja, Michael R. Charlton, Yogesh Chawla, Abhijit Chowdhury, David E. Cohen, Alessandro Demaio, Javier Diaz-Ferrer, Anna Mae Diehl, Alexander French, Cheryl Grainger, Nadege T. Gunn, Bela Hunyady, Robert James, Jia-Horm Kao, Rohit Kohli, Hye Won Lee, Cosmas Rinaldi A. Lesmana, Panu K. Luukkonen, Dina Mansour, Patrick Marcellin, Rui T. Marinho, Luca Miele, Tahiri Mohammed, Munkhjargal Ayurzana, Jude Oben, Missiani Ochwoto, Juan Paredes Méndez, Rachel Pryke, Puneet Puri, Marcus Ranney, Stuart K. Roberts, John F. Ryan, Arun J. Sanyal, Raymond Sayegh, Piotr Socha, Joan B. Soriano, Juan José Suárez, Ki-Chul Sung, Tawesak Tanwandee, Juan Turnes, Saskia van Mil, Kym Watt, Sarah H. Wild, Stavra A. Xanthakos, and Amany Zekry.

## The Healthy Livers, Healthy Lives Collaborators

Jeffrey V. Lazarus¹,¹,²,³, Henry E. Mark⁴,⁵, Alina M. Allen⁶, Juan Pablo Arab⁷,⁸,⁹, Patrizia Carrieri¹⁰, Mazen Noureddin¹¹, William Alazawi¹², Naim Alkhouri¹³, Saleh A. Alqahtani¹⁴, Marco Arrese⁹, Ramon Bataller¹⁵, Thomas Berg¹⁶, Paul N. Brennan¹⁷, Patrizia Burra¹⁸, Graciela E. Castro-Narro¹⁹,²⁰,²¹, Helena Cortez-Pinto²², Kenneth Cusi²³, Nikos Dedes²⁴, Ajay Duseja²⁵, Sven M. Francque²⁶,²⁷, Hannes Hagström²⁸, Terry T-K. Huang³,²⁹, Dana Ivancovsky Wajcman¹, Achim

Kautz³⁰, Christopher J. Kopka³¹, Aleksander Krag³², Veronica Miller³³, Philip N. Newsome³⁴, Mary E. Rinella³⁵, Diana Romero³⁶, Shiv Kumar Sarin³⁷, Marcelo Silva³⁸, C. Wendy Spearman³⁹, Emmanuel A. Tsochatzis⁴⁰, Luca Valenti⁴¹,⁴², Marcela Villoota-Rivas³¹, Shira Zelber-Sagi⁴³,⁴⁴, Jörn M. Schattenberg⁴⁵, Vincent Wai-Sun Wong⁴⁶, Zobair M. Younossi⁴⁷, Fredrik Aberg⁴⁸, Leon A. Adams⁴⁹, Khalid Al-Naamani⁵⁰, Reda M. Albadawy⁵¹, Zinaida Alexa⁵², Michael Allison⁵³, Faisal Abdullatif Alnaser⁵⁴, Khalid Alswat⁵⁵, Mario R. Alvarez-da-Silva⁵⁶, Dome-nico Alvaro⁵⁷, Michele Alves-Bezerra⁵⁸, Raul J. Andrade⁵⁹, Quentin M. Anstee⁶⁰, Yaw Asante Awuku⁶¹, Oidov Baatarkhuu⁶², Gyorgy Baffy⁶³, Shokhista R. Bakieva⁶⁴, Meena B. Bansal⁶⁵, Robert Barouki⁶⁶, Rachel L. Batterham⁶⁷, Cynthia Behling⁶⁸, Renata Belfort-DeAguiar⁶⁹, Annalisa Berzigotti⁷⁰, Michael Betel⁷¹, Cristiana Bianco⁷², Emanuele Bosi⁷³, Jerome Boursier⁷⁴, Elizabeth M. Brunt⁷⁵, Elisabetta Bugianesi⁷⁶, Christopher J. Byrne⁷⁷, Maria Cecilia Cabrera Cabrejos⁷⁸, Stephen Caldwell⁷⁹, Rotonya Carr⁸⁰, Marlen Ivón Castellanos Fernández⁸¹, Laurent Castera⁸², Maria Gabriela Castillo-López⁸³, Cyrielle Caussy⁸⁴, Eira Cerda-Reyes⁸⁵, Antonio Ceriello⁸⁶, Wah-Kheong Chan⁸⁷, Yoosoo Chang⁸⁸, Phunchai Charatcharoenwithaya⁸⁹, Norberto Chavez-Tapia⁹⁰, Raymond T. Chung⁹¹, Massimo Colombo⁹², Kirsten J. Coppell⁹³, Helma P. Cotrim⁹⁴, Antonio Craxi⁹⁵, Javier Crespo⁹⁶, Anuradha Dassanayake⁹⁷, Nicholas O. Davidson⁹⁸, Robert J. de Knecht⁹⁹, Victor de Ledinghen¹⁰⁰, Münevver Demir¹⁰¹, Hailemichael Desalegn¹⁰², Moises Diago¹⁰³, John F. Dillon⁷⁷, Bruce Dimmig¹⁰⁴, M. Ashworth Dirac¹⁰⁵, Melissa Dirchwolf¹⁰⁶, Jean-François Dufour¹⁰⁷, Karel Dvorak¹⁰⁸, Mattias Ekstedt¹⁰⁹, Mohamed El-Kassas¹¹⁰, Osama M. Elsanousi¹¹¹, Ahmed M. Elsharkawy¹¹⁴, Reda M. Elwakil¹¹², Wayne Eskridge¹¹³, Mohammed Eslam¹¹⁴, Gamal Eslam¹¹⁵, Jian-Gao Fan¹¹⁶, Maria Lucia Ferraz¹¹⁷, Robert Fliaksi¹¹⁸, Davide Fortin¹⁰, Yasser Fouad¹¹⁹, Scott L. Friedman⁶⁵, Michael Fuchs¹²⁰, Adrian Gadano¹²¹, Amalia Gastaldelli¹²², Anja Geerts¹²³, Andreas Geier¹²⁴, Jacob George¹¹⁴, Lynn H. Gerber¹²⁵, Hasmik L. Ghazinyan¹²⁶, Liana Gheorghe¹²⁷, Denise Giangola Kile¹²⁸, Marcos Girala¹²⁹, George Goh Boon Bee¹³⁰, Nicolas Goossens¹³¹, Isabel Graupera¹³², Henning Grenbæk¹³³, Saeed Hamid¹³⁴, Vanessa Hebdtch¹³⁵, Zachary Henry⁷⁹, Ingrid J. Hickman¹³⁶, L. Ansley Hobbs³, Samantha L. Hocking¹³⁷, Wolf Peter Hofmann¹³⁸, Ramazan Idilman¹³⁹, Paula Iruzubieta⁹⁶, Scott Isaacs¹⁴⁰, Vasily A. Isakov¹⁴¹, Mona H. Ismail¹⁴², Mohammad H. Jamal¹⁴³, Helen Jarvis¹⁴⁴, Peter Jepsen¹³³, François R. Jornayvaz¹⁴⁵, Sud-hamshu K.C.¹⁴⁶, Satoru Kakizaki¹⁴⁷, Saul Karpen¹⁴⁸, Takumi Kawaguchi¹⁴⁹, Shelley E. Keating¹⁵⁰, Yousef Khader¹⁵¹, Seung Up Kim¹⁵², Won Kim¹⁵³, David E. Kleiner¹⁵⁴, Ger Koek¹⁵⁵, Narcisse Patrice Joseph Komas¹⁵⁶, Liana A. Kondill¹⁵⁷, Bart G. Koot¹⁵⁸, Marko Korenjak¹⁵⁹, Eleni Kottilili¹⁶⁰, Yiannoula Koulla¹⁶¹, Carina Kugelmas¹⁶², Marcelo Kugelmas¹⁶³, Asma Labidi¹⁶⁴, Naomi F. Lange¹⁶⁵, Joel E. Lavine¹⁶⁶, Mariana Lazo¹⁶⁷, Nathalie Leite¹⁶⁸, Han-Chieh Lin¹⁶⁹, Undram Lkhagvaa⁶², Michelle T. Long¹⁷⁰, Patricio Lopez-Jaramillo¹⁷¹, Adelina Lozano¹⁷², Maria Paula Macedo¹⁷³, Reza Malekzadeh¹⁷⁴, Giulio Marchesini¹⁷⁵, Sebastian Marciano¹²¹, Kim Martinez¹⁷⁶, Sophia E. Martinez Vázquez²⁰, Lyudmila Mateva¹⁷⁷, José M. Mato¹⁷⁸, Charles N. Mbendi¹⁷⁹, Alexis Gorden McCary¹⁸⁰, Jeff McIntyre¹⁸¹, Martin McKee¹⁸², Juan M. Mendive¹⁸³, Ivana Kolasevic¹⁸⁴, Pamela S. Miller¹⁸⁵, Tamara Milovanovic¹⁸⁶, Terri Milton¹⁸⁷, Rosalba Moreno-Alcantar¹⁸⁸, Timothy R. Morgan¹⁸⁹, Ayesha A. Motala¹⁹⁰, Jean Muris¹⁹¹, Carla Musso¹⁹², Edna J. Nava-González¹⁹³, Francesco Negro¹⁹⁴, Alexander V. Nersov¹⁹⁵, Brent A. Neuschwander-Tetri¹⁹⁶, Dafina Nikolaov¹⁹⁷, Suzanne Norris¹⁹⁸, Katja Novak¹⁹⁹, Ponsiano Ocama²⁰⁰, Janus P. Ong²⁰¹, Arlinking Ong-Go²⁰², Charles Oyekwere²⁰³, P. Martin Padilla-Machaca²⁰⁴, Raluca Pais²⁰⁵, Calvin Q. Pan²⁰⁶, Arturo Panduro²⁰⁷, Manas K. Panigrah²⁰⁸, Georgios Papatheodoridis²⁰⁹, Imran Paruk¹⁹⁰, Keyur Patel²¹⁰, Carlos Penha-Goncalves²¹¹, Norma M. Pérez²¹², Juanita Pérez-Escobar²¹³, Juan M. Pericàs²¹⁴, Gianluca Perseghin²¹⁵, Mário Guimarães Pessoa²¹⁶, Salvatore Petta²¹⁷, Claudia Pinto Marques Souza de Oliveira²¹⁸, Dorairaj Prabhakaran²¹⁹, Nikolaos Pyrosopoulos²²⁰, Atoosa Rabiee²²¹, Alnoor Ramji²²², Vlad Ratziu²²³, Natarajan Ravendhran²²⁴, Katrina Ray²²⁵, Michael Roden²²⁶, Manuel Romeo²²⁷, Manuel Romero-Gómez²²⁸, Yaron Rotman²²⁹, Samir Rouabhia²³⁰, Ian A. Rowe²³¹, Shakhlo Sadirova²³², Maryam Salem Alkhatry²³³, Riina Salupere²³⁴, Sanjaya K. Satapathy²³⁵, Jeffrey B. Schwimmer²³⁶, Giada Sebastiani²³⁷, Lynn Seim²³⁸, Yosuke Seki²³⁹, Abdel Karim Serme²⁴⁰, David Shapiro²⁴¹, Lali Sharvadze²⁴², Jonathan E. Shaw²⁴³, Isaac Thom Shawa²⁴⁴, Thrivikrama Shenoy²⁴⁵, Oren Shibolet²⁴⁶, Yusuke Shimakawa²⁴⁷, Jay H. Shubrook²⁴⁸, Shivaram Prasad Singh²⁴⁹, Edford Sinkala²⁵⁰, Lubomir Skladany²⁵¹, Igor Skrypnyk²⁵², Myeong Jun Song²⁵³, Silvia Sookoian²⁵⁴, Kannan Sridharan²⁵⁵, Norbert Stefan²⁵⁶, Jonathan G. Stine²⁵⁷, Nikos Stratakis¹, Dhastagir Sultan Sheriff²⁵⁸, Shikha S. Sundaram²⁵⁹, Gianluca Svegliati-Baroni²⁶⁰, Mark G. Swain²⁶¹, Frank Tacke¹⁰¹, Shahrad Taheri²⁶², Soek-Siam Tan²⁶³, Elliot B. Tapper²⁶⁴, Giovanni Targher²⁶⁵, Eugen Tcaciu²⁶⁶, Maja Thiele²⁷, Dina Tinikos²⁶⁷, Ieva Tomka²⁶⁸, Aldo Torre²⁶⁹, Esther A. Torres²⁷⁰, Sombat Treeprasertsukt²⁷¹, Michael Trenell²⁷², Svetlana Turcan²⁶⁶, Adela Turcanu²⁶⁶, Jonas Valantinas²⁷³, Laurens A. van Kleef⁹⁹, Jose Antonio Velarde Ruiz Velasco²⁷⁴, Mette Vesterhus²⁷⁵, Eduardo Vilar-Gomez²⁷⁶, Imam Waked²⁷⁷, Julia
# Global research priority agenda for fatty liver disease

AbbVie, Gilead Sciences, Novo Nordisk, and Unilab, support for attending meetings and/or travel from AbbVie and Gilead Sciences, and unpaid stock as co-founder of Illuminatio Medical Technology Limited, outside of the submitted work. Z.M.Y acknowledges consulting fees from Gilead, Intercept, Siemens, Novo Nordisk, Madrigal, Merck, Quest, and Bristol Myers Squibb, outside of the submitted work. J.P.A, P.C, S.A.A, M.A, G.C-N, D.I.W, A.K, C.J.K, and S.K.S have no conflicts of interest to disclose.

Please refer to the accompanying ICMJE disclosure forms for further details.

## Authors' contributions

This study was led by a core group of 40 co-authors. J.V.L led the core group and provided regular updates by email. Twenty-six core group members and 11 co-authors participated in a three-day in-person meeting hosted by Wilton Park, UK, in October 2022, which informed the development of the research priorities included in the Delphi study. Seven co-chairs (A.M.A, J.P.A, P.C, M.N, J.M.S, V.W-S.W, and Z.M.Y) led the drafting of seven evidence notes, including key priorities and challenges, ahead of the Wilton Park meeting and were supported by core group members (R.B, T.B, H.C-P, K.C, N.D, A.D, T.T-K.H, A.I.K, V.M, P.N.N, M.E.R, M.S, E.T, and S.Z-S). The evidence notes were reviewed by J.V.L and H.E.M and informed the drafting of the research priorities statements and actions. D.R and J.V.L led the methodology. J.V.L, H.E.M, P.N.B, C.J.K, D.R, D.I.W, and M.V-R reviewed comments submitted as part of the two survey rounds. J.V.L., H.E.M., and M.V-R reviewed all comments sent directly by email. All panel members provided two rounds of comments through Qualtrics XM. H.E.M, M.V-R, and J.V.L wrote the first draft of the manuscript, which was reviewed by the core group. Those fulfilling authorship criteria are named.

## Data availability statement

De-identified source data for all analyses will be made available by contacting the corresponding author (Jeffrey.Lazarus@sph.cuny.edu), with appropriate ethical approval and for fair use.

## Acknowledgments

The formation of the Healthy Livers, Healthy Lives global coalition builds on three years of work led initially by the EASL International Liver Foundation (EILF) and since 2021 by EASL. Collaboration has been at the centre of this work. Over 500 individuals and organisations spanning over 100 countries have engaged in these efforts, with multiple disciplines and sectors represented, including affected populations. As part of this process, in October 2022, delegates, including representatives from EASL, the American Association for the Study of Liver Diseases (AASLD), the Latin American Association for the Study of the Liver (Asociación Latinoamericana para el Estudio del Hígado [ALEH]) (representatives of the Asian Pacific Association for the Study of the Liver [APASL] were unable to attend), the Society on Liver Disease in Africa (SOLDA), the European Association for the Study of Diabetes (EASD), the European Association for the Study of Obesity (EASO), the European Society of Primary Care Gastroenterology (ESPCG), the Global NASH Council (GNC), United European Gastroenterology (UEG), the World Obesity Federation (WOF), and the World Organization of Family Doctors (WONCA), gathered for three days of discussion at Wilton Park, a UK-based forum for strategic dialogue.

We are grateful to the following experts for their contributions to the Delphi process: Manal F. Abdelmalek, Abdelmounem E. Abdo, Matthew J. Armstrong, Carol L. Brosgart, José Luis Calleja, Michael R. Charlton, Yogesh Chawla, Abhijit Chowdhury, David E. Cohen, Alessandro Demaio, Javier Diaz-Ferrer, Anna Mae Diehl, Alexander French, Cheryl Grainger, Nadege T. Gunn, Bela Hunyady, Robert James, Jia-Horng Kao, Rohit Kohli, Hye Won Lee, Cosmas Rinaldi A. Lesmana, Panu K. Luukkonen, Dina Mansour, Patrick Marcellin, Rui T. Marinho, Luca Miele, Tahiri Mohammed, Munkhjargal Ayurzana, Jude Oben, Missiani Ochwoto, Juan Paredes Méndez, Rachel Pryke, Puneet Puri, Marcus Ranney, Stuart K. Roberts, John F. Ryan, Arun J. Sanyal, Raymond Sayegh, Piotr Socha, Joan B. Soriano, Juan José Suárez, Ki-Chul Sung, Tawesak Tanwandee, Juan Turnes, Saskia van Mil, Kym Watt, Sarah H. Wild, Stavra A. Xanthakos, and Amany Zekry.

## The Healthy Livers, Healthy Lives Collaborators

Jeffrey V. Lazarus¹,¹,²,³, Henry E. Mark⁴,⁵, Alina M. Allen⁶, Juan Pablo Arab⁷,⁸,⁹, Patrizia Carrieri¹⁰, Mazen Noureddin¹¹, William Alazawi¹², Naim Alkhouri¹³, Saleh A. Alqahtani¹⁴, Marco Arrese⁹, Ramon Bataller¹⁵, Thomas Berg¹⁶, Paul N. Brennan¹⁷, Patrizia Burra¹⁸, Graciela E. Castro-Narro¹⁹,²⁰,²¹, Helena Cortez-Pinto²², Kenneth Cusi²³, Nikos Dedes²⁴, Ajay Duseja²⁵, Sven M. Francque²⁶,²⁷, Hannes Hagström²⁸, Terry T-K. Huang³,²⁹, Dana Ivancovsky Wajcman¹, Achim

Kautz³⁰, Christopher J. Kopka³¹, Aleksander Krag³², Veronica Miller³³, Philip N. Newsome³⁴, Mary E. Rinella³⁵, Diana Romero³⁶, Shiv Kumar Sarin³⁷, Marcelo Silva³⁸, C. Wendy Spearman³⁹, Emmanuel A. Tsochatzis⁴⁰, Luca Valenti⁴¹,⁴², Marcela Villoota-Rivas³¹, Shira Zelber-Sagi⁴³,⁴⁴, Jörn M. Schattenberg⁴⁵, Vincent Wai-Sun Wong⁴⁶, Zobair M. Younossi⁴⁷, Fredrik Aberg⁴⁸, Leon A. Adams⁴⁹, Khalid Al-Naamani⁵⁰, Reda M. Albadawy⁵¹, Zinaida Alexa⁵², Michael Allison⁵³, Faisal Abdullatif Alnaser⁵⁴, Khalid Alswat⁵⁵, Mario R. Alvarez-da-Silva⁵⁶, Dome-nico Alvaro⁵⁷, Michele Alves-Bezerra⁵⁸, Raul J. Andrade⁵⁹, Quentin M. Anstee⁶⁰, Yaw Asante Awuku⁶¹, Oidov Baatarkhuu⁶², Gyorgy Baffy⁶³, Shokhista R. Bakieva⁶⁴, Meena B. Bansal⁶⁵, Robert Barouki⁶⁶, Rachel L. Batterham⁶⁷, Cynthia Behling⁶⁸, Renata Belfort-DeAguiar⁶⁹, Annalisa Berzigotti⁷⁰, Michael Betel⁷¹, Cristiana Bianco⁷², Emanuele Bosi⁷³, Jerome Boursier⁷⁴, Elizabeth M. Brunt⁷⁵, Elisabetta Bugianesi⁷⁶, Christopher J. Byrne⁷⁷, Maria Cecilia Cabrera Cabrejos⁷⁸, Stephen Caldwell⁷⁹, Rotonya Carr⁸⁰, Marlen Ivón Castellanos Fernández⁸¹, Laurent Castera⁸², Maria Gabriela Castillo-López⁸³, Cyrielle Caussy⁸⁴, Eira Cerda-Reyes⁸⁵, Antonio Ceriello⁸⁶, Wah-Kheong Chan⁸⁷, Yoosoo Chang⁸⁸, Phunchai Charatcharoenwithaya⁸⁹, Norberto Chavez-Tapia⁹⁰, Raymond T. Chung⁹¹, Massimo Colombo⁹², Kirsten J. Coppell⁹³, Helma P. Cotrim⁹⁴, Antonio Craxi⁹⁵, Javier Crespo⁹⁶, Anuradha Dassanayake⁹⁷, Nicholas O. Davidson⁹⁸, Robert J. de Knecht⁹⁹, Victor de Ledinghen¹⁰⁰, Münevver Demir¹⁰¹, Hailemichael Desalegn¹⁰², Moises Diago¹⁰³, John F. Dillon⁷⁷, Bruce Dimmig¹⁰⁴, M. Ashworth Dirac¹⁰⁵, Melissa Dirchwolf¹⁰⁶, Jean-François Dufour¹⁰⁷, Karel Dvorak¹⁰⁸, Mattias Ekstedt¹⁰⁹, Mohamed El-Kassas¹¹⁰, Osama M. Elsanousi¹¹¹, Ahmed M. Elsharkawy¹¹⁴, Reda M. Elwakil¹¹², Wayne Eskridge¹¹³, Mohammed Eslam¹¹⁴, Gamal Eslam¹¹⁵, Jian-Gao Fan¹¹⁶, Maria Lucia Ferraz¹¹⁷, Robert Fliaksi¹¹⁸, Davide Fortin¹⁰, Yasser Fouad¹¹⁹, Scott L. Friedman⁶⁵, Michael Fuchs¹²⁰, Adrian Gadano¹²¹, Amalia Gastaldelli¹²², Anja Geerts¹²³, Andreas Geier¹²⁴, Jacob George¹¹⁴, Lynn H. Gerber¹²⁵, Hasmik L. Ghazinyan¹²⁶, Liana Gheorghe¹²⁷, Denise Giangola Kile¹²⁸, Marcos Girala¹²⁹, George Goh Boon Bee¹³⁰, Nicolas Goossens¹³¹, Isabel Graupera¹³², Henning Grenbæk¹³³, Saeed Hamid¹³⁴, Vanessa Hebdtch¹³⁵, Zachary Henry⁷⁹, Ingrid J. Hickman¹³⁶, L. Ansley Hobbs³, Samantha L. Hocking¹³⁷, Wolf Peter Hofmann¹³⁸, Ramazan Idilman¹³⁹, Paula Iruzubieta⁹⁶, Scott Isaacs¹⁴⁰, Vasily A. Isakov¹⁴¹, Mona H. Ismail¹⁴², Mohammad H. Jamal¹⁴³, Helen Jarvis¹⁴⁴, Peter Jepsen¹³³, François R. Jornayvaz¹⁴⁵, Sud-hamshu K.C.¹⁴⁶, Satoru Kakizaki¹⁴⁷, Saul Karpen¹⁴⁸, Takumi Kawaguchi¹⁴⁹, Shelley E. Keating¹⁵⁰, Yousef Khader¹⁵¹, Seung Up Kim¹⁵², Won Kim¹⁵³, David E. Kleiner¹⁵⁴, Ger Koek¹⁵⁵, Narcisse Patrice Joseph Komas¹⁵⁶, Liana A. Kondill¹⁵⁷, Bart G. Koot¹⁵⁸, Marko Korenjak¹⁵⁹, Eleni Kottilili¹⁶⁰, Yiannoula Koulla¹⁶¹, Carina Kugelmas¹⁶², Marcelo Kugelmas¹⁶³, Asma Labidi¹⁶⁴, Naomi F. Lange¹⁶⁵, Joel E. Lavine¹⁶⁶, Mariana Lazo¹⁶⁷, Nathalie Leite¹⁶⁸, Han-Chieh Lin¹⁶⁹, Undram Lkhagvaa⁶², Michelle T. Long¹⁷⁰, Patricio Lopez-Jaramillo¹⁷¹, Adelina Lozano¹⁷², Maria Paula Macedo¹⁷³, Reza Malekzadeh¹⁷⁴, Giulio Marchesini¹⁷⁵, Sebastian Marciano¹²¹, Kim Martinez¹⁷⁶, Sophia E. Martinez Vázquez²⁰, Lyudmila Mateva¹⁷⁷, José M. Mato¹⁷⁸, Charles N. Mbendi¹⁷⁹, Alexis Gorden McCary¹⁸⁰, Jeff McIntyre¹⁸¹, Martin McKee¹⁸², Juan M. Mendive¹⁸³, Ivana Kolasevic¹⁸⁴, Pamela S. Miller¹⁸⁵, Tamara Milovanovic¹⁸⁶, Terri Milton¹⁸⁷, Rosalba Moreno-Alcantar¹⁸⁸, Timothy R. Morgan¹⁸⁹, Ayesha A. Motala¹⁹⁰, Jean Muris¹⁹¹, Carla Musso¹⁹², Edna J. Nava-González¹⁹³, Francesco Negro¹⁹⁴, Alexander V. Nersov¹⁹⁵, Brent A. Neuschwander-Tetri¹⁹⁶, Dafina Nikolaov¹⁹⁷, Suzanne Norris¹⁹⁸, Katja Novak¹⁹⁹, Ponsiano Ocama²⁰⁰, Janus P. Ong²⁰¹, Arlinking Ong-Go²⁰², Charles Oyekwere²⁰³, P. Martin Padilla-Machaca²⁰⁴, Raluca Pais²⁰⁵, Calvin Q. Pan²⁰⁶, Arturo Panduro²⁰⁷, Manas K. Panigrah²⁰⁸, Georgios Papatheodoridis²⁰⁹, Imran Paruk¹⁹⁰, Keyur Patel²¹⁰, Carlos Penha-Goncalves²¹¹, Norma M. Pérez²¹², Juanita Pérez-Escobar²¹³, Juan M. Pericàs²¹⁴, Gianluca Perseghin²¹⁵, Mário Guimarães Pessoa²¹⁶, Salvatore Petta²¹⁷, Claudia Pinto Marques Souza de Oliveira²¹⁸, Dorairaj Prabhakaran²¹⁹, Nikolaos Pyrosopoulos²²⁰, Atoosa Rabiee²²¹, Alnoor Ramji²²², Vlad Ratziu²²³, Natarajan Ravendhran²²⁴, Katrina Ray²²⁵, Michael Roden²²⁶, Manuel Romeo²²⁷, Manuel Romero-Gómez²²⁸, Yaron Rotman²²⁹, Samir Rouabhia²³⁰, Ian A. Rowe²³¹, Shakhlo Sadirova²³², Maryam Salem Alkhatry²³³, Riina Salupere²³⁴, Sanjaya K. Satapathy²³⁵, Jeffrey B. Schwimmer²³⁶, Giada Sebastiani²³⁷, Lynn Seim²³⁸, Yosuke Seki²³⁹, Abdel Karim Serme²⁴⁰, David Shapiro²⁴¹, Lali Sharvadze²⁴², Jonathan E. Shaw²⁴³, Isaac Thom Shawa²⁴⁴, Thrivikrama Shenoy²⁴⁵, Oren Shibolet²⁴⁶, Yusuke Shimakawa²⁴⁷, Jay H. Shubrook²⁴⁸, Shivaram Prasad Singh²⁴⁹, Edford Sinkala²⁵⁰, Lubomir Skladany²⁵¹, Igor Skrypynyk²⁵², Myeong Jun Song²⁵³, Silvia Sookoian²⁵⁴, Kannan Sridharan²⁵⁵, Norbert Stefan²⁵⁶, Jonathan G. Stine²⁵⁷, Nikos Stratakis¹, Dhastagir Sultan Sheriff²⁵⁸, Shikha S. Sundaram²⁵⁹, Gianluca Svegliati-Baroni²⁶⁰, Mark G. Swain²⁶¹, Frank Tacke¹⁰¹, Shahrad Taheri²⁶², Soek-Siam Tan²⁶³, Elliot B. Tapper²⁶⁴, Giovanni Targher²⁶⁵, Eugen Tcaciu²⁶⁶, Maja Thiele²⁷, Dina Tinikos²⁶⁷, Ieva Tomka²⁶⁸, Aldo Torre²⁶⁹, Esther A. Torres²⁷⁰, Sombat Treeprasertsukt²⁷¹, Michael Trenell²⁷², Svetlana Turcan²⁶⁶, Adela Turcanu²⁶⁶, Jonas Valantinas²⁷³, Laurens A. van Kleef⁹⁹, Jose Antonio Velarde Ruiz Velasco²⁷⁴, Mette Vesterhus²⁷⁵, Eduardo Vilar-Gomez²⁷⁶, Imam Waked²⁷⁷, Julia
Wattacherl²⁷⁸, Heiner Wedemeyer²⁷⁹, Fonda Wilkins²⁸⁰, José Willemse²⁸¹, Robert J. Wong²⁸², Yusuf Yilmaz²⁸³, Hannele Yki-Järvinen²⁸⁴, Ming-Lung Yu²⁸⁵, Volkan Yumuk²⁸⁶, Müjdat Zeybel²⁸⁷, Kenneth I. Zheng²⁸⁸, Ming-Hua Zheng²⁸⁸
*Contributed equally.

¹Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, University of Barcelona, Barcelona, Spain

²Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain

³CUNY Graduate School of Public Health and Health Policy (CUNY SPH), New York, NY, USA

⁴European Association for the Study of the Liver (EASL), Geneva, Switzerland

⁵Independent consultant, Nottingham, UK

⁶Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA

⁷Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada

⁸Department of Epidemiology and Biostatistics, Schulich School of Medicine, Western University, London, Ontario, Canada

⁹Department of Gastroenterology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile

¹Aix Marseille Univ, Inserm, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale, ISSPAM, Marseille, France

¹¹Houston Methodist Hospital, Houston Research Institute, Houston, TX, USA

¹²Barts Liver Centre, Blizard Institute, Queen Mary University of London, London, UK

¹³Fatty Liver Program, Arizona Liver Health, Phoenix, AZ, USA

¹⁴King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia

¹⁵Liver Unit, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

¹⁶Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany

¹⁷Division of Hepatology, University of Dundee, Dundee, Scotland, UK

¹⁸Multivisceral Transplant Unit-Gastroenterology, Department of Surgery, Oncology and Gastroenterology at the Padua University Hospital, Padua, Italy

¹⁹Department of Hepatology and Transplant, Hospital Médica Sur, Mexico City, Mexico

²⁰Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

²¹Asociación Latinoamericana para el Estudio del Hígado (ALEH), Santiago, Chile

²²Clinica Universitária de Gastrenterologia, Laboratório de Nutrição, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal

²³Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, University of Florida, Gainesville, FL, USA

²⁴Greek Patients Association, Athens, Greece

²⁵Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

²⁶Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, Belgium

²⁷InflaMed Centre of Excellence, Laboratory for Experimental Medicine and Paediatrics, Translational Sciences in Inflammation and Immunology, Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk, Belgium

²⁸Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden

²⁹CUNY Center for Systems and Community Design and NYU-CUNY Prevention Research Center, New York, NY, USA

³⁰Kautz 5 gUG, Köln, Germany

³¹Independent researcher, Ponte de Lima, Portugal

³²Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark

³³University California Berkeley School of Public Health, Berkeley, CA, USA

³⁴National Institute for Health Research Birmingham Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham, Birmingham, UK

³⁵Department of Medicine, University of Chicago, Chicago, IL, USA

³⁶Department of Community Health and Social Sciences, CUNY Graduate School of Public Health and Health Policy, New York, NY, USA

³⁷Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India

³⁸Hepatology and Clinical Research Units, Hospital Universitario Austral, Buenos Aires, Argentina

³⁹Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa

⁴⁰UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK

⁴¹Precision Medicine, Biological Resource Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy

⁴²Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy

⁴³School of Public Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel

⁴⁴Department of Gastroenterology, Tel Aviv Medical Centre, Tel Aviv, Israel

⁴⁵Metabolic Liver Research Program, I. Department of Medicine, University Medical Center Mainz, Mainz, Germany

⁴⁶The Chinese University of Hong Kong, Hong Kong, China

⁴⁷Center for Liver Disease, Inova, Falls Church, VA, USA

⁴⁸Transplantation and Liver Surgery, Helsinki University Hospital, Helsinki, Finland

⁴⁹Medical School, The University of Western Australia, Perth, Western Australia, Australia

⁵⁰Department of Internal Medicine, Division of Gastroenterology and Hepatology, Armed Forces Hospital, Muscat, Oman

⁵¹Gastroenterology, Hepatology & Infectious Diseases Department, Benha University, Benha, Egypt

⁵²Republican Clinical Hospital "Timofei Mosneaga", Chișinău, Republic of Moldova

⁵³Liver Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK

⁵⁴Department of Primary Care & Public Health, Faculty of Medicine, Imperial College, London, UK

⁵⁵Liver Disease Research Center, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia

⁵⁶School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

⁵⁷Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

⁵⁸Department of Biomedicine, Biotechnology and Public Health, University of Cadiz, Cadiz, Spain

⁵⁹Servicio de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Universidad de Málaga, Málaga, Spain

⁶⁰Translational & Clinical Research Institute, Faculty of Medical Science, Newcastle University, Newcastle upon Tyne, UK

⁶¹University of Health and Allied Science, Ho, Ghana

⁶²Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia

⁶³VA Boston Healthcare System and Harvard Medical School, Boston, MA, USA

⁶⁴Scientific Department, The Research Institute of Virology of the MoH of the Republic of Uzbekistan, Tashkent, Uzbekistan

⁶⁵Icahn School of Medicine at Mount Sinai, New York, NY, USA

⁶⁶Université Paris Cité, Inserm T³S, Paris, France

⁶⁷Centre for Obesity Research, Department of Medicine, University College London, London, UK

⁶⁸Pacific Rim Pathology Group, San Diego, CA, USA

⁶⁹Internal Medicine Department, Yale University, New Haven, CT, USA

⁷⁰Department of Visceral Surgery and Medicine, Bern University Hospital, University of Bern, Bern, Switzerland

⁷¹Fatty Liver Alliance, Toronto, Ontario, Canada

⁷²Precision Medicine Lab, Biological Resource Center, and Transfusion Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy

⁷³IRCCS Ospedale San Raffaele, Milan, Italy

⁷⁴Angers University & Angers University Hospital, Angers, France

⁷⁵Dept. of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA

⁷⁶Dept. of Medical Sciences, University of Torino, Torino, Italy

⁷⁷School of Medicine, University of Dundee, Dundee, Scotland, UK

⁷⁸Liver Unit, Hospital G. Almenara, Universidad Mayor de San Marcos, Lima, Peru

⁷⁹Department of Medicine, University of Virginia, Charlottesville, VA, USA

⁸⁰Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, WA, USA

⁸¹Institute of Gastroenterology, La Havana, Cuba

⁸²Université Paris Cité, Department of Hepatology, Hospital Beaujon, AP-HP, Clichy, Paris, France

⁸³Departamento Unidad Metabólica, Hospital Universitario Fundación Favaloro, Buenos Aires, Argentina

⁸⁴Endocrinology Diabetes Nutrition Hospices Civils de Lyon, Lyon, France
Wattacherl²⁷⁸, Heiner Wedemeyer²⁷⁹, Fonda Wilkins²⁸⁰, José Willemse²⁸¹, Robert J. Wong²⁸², Yusuf Yilmaz²⁸³, Hannele Yki-Järvinen²⁸⁴, Ming-Lung Yu²⁸⁵, Volkan Yumuk²⁸⁶, Müjdat Zeybel²⁸⁷, Kenneth I. Zheng²⁸⁸, Ming-Hua Zheng²⁸⁸
*Contributed equally.

¹Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, University of Barcelona, Barcelona, Spain

²Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain

³CUNY Graduate School of Public Health and Health Policy (CUNY SPH), New York, NY, USA

⁴European Association for the Study of the Liver (EASL), Geneva, Switzerland

⁵Independent consultant, Nottingham, UK

⁶Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA

⁷Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada

⁸Department of Epidemiology and Biostatistics, Schulich School of Medicine, Western University, London, Ontario, Canada

⁹Department of Gastroenterology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile

¹Aix Marseille Univ, Inserm, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale, ISSPAM, Marseille, France

¹¹Houston Methodist Hospital, Houston Research Institute, Houston, TX, USA

¹²Barts Liver Centre, Blizard Institute, Queen Mary University of London, London, UK

¹³Fatty Liver Program, Arizona Liver Health, Phoenix, AZ, USA

¹⁴King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia

¹⁵Liver Unit, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

¹⁶Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany

¹⁷Division of Hepatology, University of Dundee, Dundee, Scotland, UK

¹⁸Multivisceral Transplant Unit-Gastroenterology, Department of Surgery, Oncology and Gastroenterology at the Padua University Hospital, Padua, Italy

¹⁹Department of Hepatology and Transplant, Hospital Médica Sur, Mexico City, Mexico

²⁰Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

²¹Asociación Latinoamericana para el Estudio del Hígado (ALEH), Santiago, Chile

²²Clinica Universitária de Gastrenterologia, Laboratório de Nutrição, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal

²³Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, University of Florida, Gainesville, FL, USA

²⁴Greek Patients Association, Athens, Greece

²⁵Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

²⁶Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, Belgium

²⁷InflaMed Centre of Excellence, Laboratory for Experimental Medicine and Paediatrics, Translational Sciences in Inflammation and Immunology, Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk, Belgium

²⁸Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden

²⁹CUNY Center for Systems and Community Design and NYU-CUNY Prevention Research Center, New York, NY, USA

³⁰Kautz 5 gUG, Köln, Germany

³¹Independent researcher, Ponte de Lima, Portugal

³²Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark

³³University California Berkeley School of Public Health, Berkeley, CA, USA

³⁴National Institute for Health Research Birmingham Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham, Birmingham, UK

³⁵Department of Medicine, University of Chicago, Chicago, IL, USA

³⁶Department of Community Health and Social Sciences, CUNY Graduate School of Public Health and Health Policy, New York, NY, USA

³⁷Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India

³⁸Hepatology and Clinical Research Units, Hospital Universitario Austral, Buenos Aires, Argentina

³⁹Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa

⁴⁰UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK

⁴¹Precision Medicine, Biological Resource Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy

⁴²Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy

⁴³School of Public Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel

⁴⁴Department of Gastroenterology, Tel Aviv Medical Centre, Tel Aviv, Israel

⁴⁵Metabolic Liver Research Program, I. Department of Medicine, University Medical Center Mainz, Mainz, Germany

⁴⁶The Chinese University of Hong Kong, Hong Kong, China

⁴⁷Center for Liver Disease, Inova, Falls Church, VA, USA

⁴⁸Transplantation and Liver Surgery, Helsinki University Hospital, Helsinki, Finland

⁴⁹Medical School, The University of Western Australia, Perth, Western Australia, Australia

⁵⁰Department of Internal Medicine, Division of Gastroenterology and Hepatology, Armed Forces Hospital, Muscat, Oman

⁵¹Gastroenterology, Hepatology & Infectious Diseases Department, Benha University, Benha, Egypt

⁵²Republican Clinical Hospital "Timofei Mosneaga", Chișinău, Republic of Moldova

⁵³Liver Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK

⁵⁴Department of Primary Care & Public Health, Faculty of Medicine, Imperial College, London, UK

⁵⁵Liver Disease Research Center, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia

⁵⁶School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

⁵⁷Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

⁵⁸Department of Biomedicine, Biotechnology and Public Health, University of Cadiz, Cadiz, Spain

⁵⁹Servicio de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Universidad de Málaga, Málaga, Spain

⁶⁰Translational & Clinical Research Institute, Faculty of Medical Science, Newcastle University, Newcastle upon Tyne, UK

⁶¹University of Health and Allied Science, Ho, Ghana

⁶²Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia

⁶³VA Boston Healthcare System and Harvard Medical School, Boston, MA, USA

⁶⁴Scientific Department, The Research Institute of Virology of the MoH of the Republic of Uzbekistan, Tashkent, Uzbekistan

⁶⁵Icahn School of Medicine at Mount Sinai, New York, NY, USA

⁶⁶Université Paris Cité, Inserm T³S, Paris, France

⁶⁷Centre for Obesity Research, Department of Medicine, University College London, London, UK

⁶⁸Pacific Rim Pathology Group, San Diego, CA, USA

⁶⁹Internal Medicine Department, Yale University, New Haven, CT, USA

⁷⁰Department of Visceral Surgery and Medicine, Bern University Hospital, University of Bern, Bern, Switzerland

⁷¹Fatty Liver Alliance, Toronto, Ontario, Canada

⁷²Precision Medicine Lab, Biological Resource Center, and Transfusion Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy

⁷³IRCCS Ospedale San Raffaele, Milan, Italy

⁷⁴Angers University & Angers University Hospital, Angers, France

⁷⁵Dept. of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA

⁷⁶Dept. of Medical Sciences, University of Torino, Torino, Italy

⁷⁷School of Medicine, University of Dundee, Dundee, Scotland, UK

⁷⁸Liver Unit, Hospital G. Almenara, Universidad Mayor de San Marcos, Lima, Peru

⁷⁹Department of Medicine, University of Virginia, Charlottesville, VA, USA

⁸⁰Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, WA, USA

⁸¹Institute of Gastroenterology, La Havana, Cuba

⁸²Université Paris Cité, Department of Hepatology, Hospital Beaujon, AP-HP, Clichy, Paris, France

⁸³Departamento Unidad Metabólica, Hospital Universitario Fundación Favaloro, Buenos Aires, Argentina

⁸⁴Endocrinology Diabetes Nutrition Hospices Civils de Lyon, Lyon, France
Global research priority agenda for fatty liver disease

<footnote n="85">⁸⁵Central Military Hospital, Asociación Latinoamericana para el Estudio del Higado, Mexico City, Mexico</footnote>

<footnote n="86">⁸⁶IRCCS MultiMedica, Milan, Italy</footnote>

<footnote n="87">⁸⁷Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia</footnote>

<footnote n="88">⁸⁸Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea</footnote>

<footnote n="89">⁸⁹Faculty of Medicine Siriraj Hospital, Bangkok, Thailand</footnote>

<footnote n="90">⁹⁰Médica Sur Clinic & Foundation, Mexico City, Mexico</footnote>

<footnote n="91">⁹¹Liver Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA</footnote>

<footnote n="92">⁹²European Association for the Study of the Liver (EASL) International Liver Foundation, Geneva, Switzerland</footnote>

<footnote n="93">⁹³Department of Medicine, University of Otago, Wellington, New Zealand</footnote>

<footnote n="94">⁹⁴School of Medicine, Federal University of Bahia, Salvador, Brazil</footnote>

<footnote n="95">⁹⁵School of Medicine, University of Palermo, Palermo, Italy</footnote>

<footnote n="96">⁹⁶Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqués de Valdecilla University Hospital, Santander, Spain</footnote>

<footnote n="97">⁹⁷Faculty of Medicine, University of Kelaniya, Kelaniya, Sri Lanka</footnote>

<footnote n="98">⁹⁸Washington University School of Medicine, St. Louis, MO 63110, USA</footnote>

<footnote n="99">⁹⁹Erasmus MC University Medical Center, Rotterdam, the Netherlands</footnote>

<footnote n="10">¹⁰CHU Bordeaux, Bordeaux, France</footnote>

<footnote n="101">¹⁰¹Department of Hepatology & Gastroenterology, Charité - Universitätsmedizin Berlin, Berlin, Germany</footnote>

<footnote n="102">¹⁰²St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia</footnote>

<footnote n="103">¹⁰³Digestive Diseases Department, Hospital General Universitario de Valencia, Valencia, Spain</footnote>

<footnote n="104">¹⁰⁴Banner Liver Support Group, Phoenix, AZ, USA</footnote>

<footnote n="105">¹⁰⁵Department of Family Medicine, University of Washington, Seattle, WA, USA</footnote>

<footnote n="106">¹⁰⁶Liver Unit, Hospital Privado de Rosario, Rosario, Argentina</footnote>

<footnote n="107">¹⁰⁷Centre des Maladies Digestives Lausanne, Lausanne, Switzerland</footnote>

<footnote n="108">¹⁰⁸Fourth Department of Internal Medicine, First Faculty of Medicine, Charles University, Prague, Czech Republic</footnote>

<footnote n="109">¹⁰⁹Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden</footnote>

<footnote n="110">¹¹⁰Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt</footnote>

<footnote n="111">¹¹¹Department of Surgery, Faculty of Medicine, National Ribat University, Khartoum, Sudan</footnote>

<footnote n="112">¹¹²Tropical Medicine Department, Ain Shams University, Cairo, Egypt</footnote>

<footnote n="113">¹¹³Fatty Liver Foundation, Boise, ID, USA</footnote>

<footnote n="114">¹¹⁴Storr Liver Centre, Westmead Hospital, Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia</footnote>

<footnote n="115">¹¹⁵Endemic Medicine Department, Cairo University, Cairo, Egypt</footnote>

<footnote n="116">¹¹⁶Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai, China</footnote>

<footnote n="117">¹¹⁷Federal University of Sao Paulo, São Paulo, Brazil</footnote>

<footnote n="118">¹¹⁸Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland</footnote>

<footnote n="119">¹¹⁹Faculty of Medicine, Minia University, Minya, Egypt</footnote>

<footnote n="120">¹²⁰Central Virginia VA Health Care System and Virginia Commonwealth University, Richmond, VA, USA</footnote>

<footnote n="121">¹²¹Liver Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina</footnote>

<footnote n="122">¹²²Institute of Clinical Physiology, National Research Council, Pisa, Italy</footnote>

<footnote n="123">¹²³Department of Gastroenterology & Hepatology, University Hospital Ghent, Ghent, Belgium</footnote>

<footnote n="124">¹²⁴Division of Hepatology, University Hospital Wuerzburg, Wuerzburg, Germany</footnote>

<footnote n="125">¹²⁵Beatty Liver and Obesity Center, Inova Health System, Falls Church, VA, USA</footnote>

<footnote n="126">¹²⁶Nikomed Medical Centre, Yerevan, Armenia</footnote>

<footnote n="127">¹²⁷Carol Davila University of Medicine and Pharmacy, Bucharest, Romania</footnote>

<footnote n="128">¹²⁸Independent participant, Myrtle Beach, SC, USA</footnote>

<footnote n="129">¹²⁹Departamento de Gastroenterologia, Hospital de Clínicas, Universidade Nacional de Asunción, San Lorenzo, Paraguay</footnote>

<footnote n="130">¹³⁰Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore</footnote>

<footnote n="131">¹³¹Division of Gastroenterology and Hepatology, Geneva University Hospital, Geneva, Switzerland</footnote>

<footnote n="132">¹³²Liver Unit, Hospital Clínic, FCRB-IDIBAPS, University of Barcelona, Barcelona, Spain</footnote>

<footnote n="133">¹³³Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark</footnote>

<footnote n="134">¹³⁴Department of Medicine, Aga Khan University, Karachi, Pakistan</footnote>

<footnote n="135">¹³⁵British Liver Trust, Winchester, UK</footnote>

<footnote n="136">¹³⁶Department of Nutrition and Dietetics, Princess Alexandra Hospital, Brisbane, Queensland, Australia</footnote>

<footnote n="137">¹³⁷Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia</footnote>

<footnote n="138">¹³⁸Medical Care Center for Gastroenterology Bayerischer Platz, Berlin, Germany</footnote>

<footnote n="139">¹³⁹Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey</footnote>

<footnote n="140">¹⁴⁰Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA</footnote>

<footnote n="141">¹⁴¹Department of Gastroenterology & Hepatology, Federal Research Centre of Nutrition, Biotechnology & Food Safety, Moscow, Russia</footnote>

<footnote n="142">¹⁴²King Fahd Hospital of the University, Al-Khobar, and College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia</footnote>

<footnote n="143">¹⁴³Department of Transplantation and Surgery, Kuwait University, Kuwait City, Kuwait</footnote>

<footnote n="144">¹⁴⁴Newcastle University, Newcastle, UK</footnote>

<footnote n="145">¹⁴⁵Geneva University Hospital, Geneva, Switzerland</footnote>

<footnote n="146">¹⁴⁶National Academy of Medical Sciences, Kathmandu, Nepal</footnote>

<footnote n="147">¹⁴⁷Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan</footnote>

<footnote n="148">¹⁴⁸Emory University School of Medicine, Atlanta, GA, USA</footnote>

<footnote n="149">¹⁴⁹Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan</footnote>

<footnote n="150">¹⁵⁰School of Human Movement and Nutrition Sciences, The University of Queensland, Brisbane, Queensland, Australia</footnote>

<footnote n="151">¹⁵¹Department of Public Health, Jordan University of Science and Technology, Irbid, Jordan</footnote>

<footnote n="152">¹⁵²Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea</footnote>

<footnote n="153">¹⁵³Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea</footnote>

<footnote n="154">¹⁵⁴Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA</footnote>

<footnote n="155">¹⁵⁵Maastricht University Medical Center, Maastricht, the Netherlands</footnote>

<footnote n="156">¹⁵⁶Institut Pasteur de Bangui, Bangui, Central African Republic</footnote>

<footnote n="157">¹⁵⁷Center for Global Health, Istituto Superiore Di Sanità (ISS), UniCamillus-Saint Camillus International University of Health Sciences, Rome, Italy</footnote>

<footnote n="158">¹⁵⁸Department of Pediatric Gastroenterology, Emma's Children Hospital, Amsterdam University Medical Center, Amsterdam, the Netherlands</footnote>

<footnote n="159">¹⁵⁹Department of Liver Patients' Association, Brussels, Belgium</footnote>

<footnote n="160">¹⁶⁰Nature Reviews Gastroenterology & Hepatology, Berlin, Germany</footnote>

<footnote n="161">¹⁶¹Cyprus Liver Patients Association, Nicosia, Cyprus</footnote>

<footnote n="162">¹⁶²Department of Pediatrics, Denver Health Medical Center, Denver, CO, USA</footnote>

<footnote n="163">¹⁶³South Denver Gastroenterology, Englewood, CO, USA</footnote>

<footnote n="164">¹⁶⁴Gastroenterology "A" Department, Rabta University Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia</footnote>

<footnote n="165">¹⁶⁵Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland</footnote>

<footnote n="166">¹⁶⁶Department of Pediatrics, Columbia University, New York, NY, USA</footnote>

<footnote n="167">¹⁶⁷Urban Health Collaborative, Dornsife School of Public Health, Drexel University, Philadelphia, PA, USA</footnote>

<footnote n="168">¹⁶⁸Department of Internal Medicine, University Hospital Clementino Fraga Filho, School of Medicine, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil</footnote>

<footnote n="169">¹⁶⁹Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan</footnote>

<footnote n="170">¹⁷⁰Novo Nordisk A/S, Vandtårnsvæj 108-110, 2860 Søborg, Denmark</footnote>

<footnote n="171">¹⁷¹Masira Research Institute, Medical School, Universidad de Santander (UDES), Bucaramanga, Colombia</footnote>

<footnote n="172">¹⁷²Cayetano Heredia Peruvian University, Lima, Peru</footnote>

<footnote n="173">¹⁷³INOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisbon, Portugal</footnote>

<footnote n="174">¹⁷⁴Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran</footnote>

<footnote n="175">¹⁷⁵Alma Mater-University of Bologna, Bologna, Italy</footnote>

<footnote n="176">¹⁷⁶GLI, Lakewood, NJ, USA</footnote>

<footnote n="177">¹⁷⁷University Hospital "St Ivan Rilski", Medical University of Sofia, Sofia, Bulgaria</footnote>

<footnote n="178">¹⁷⁸CIC bioGUNE, Technology Park of Bizkaia, Derio, Spain</footnote>

<footnote n="179">¹⁷⁹Service of Hepatology and Gastroenterology, Department of Internal Medicine, University Clinics of Kinshasa, Kinshasa, Democratic Republic of the Congo</footnote>

<footnote n="180">¹⁸⁰Mid-Atlantic Permanent Medical Group, Rockville, MD, USA</footnote>
Global research priority agenda for fatty liver disease

<footnote n="85">⁸⁵Central Military Hospital, Asociación Latinoamericana para el Estudio del Higado, Mexico City, Mexico</footnote>

<footnote n="86">⁸⁶IRCCS MultiMedica, Milan, Italy</footnote>

<footnote n="87">⁸⁷Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia</footnote>

<footnote n="88">⁸⁸Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea</footnote>

<footnote n="89">⁸⁹Faculty of Medicine Siriraj Hospital, Bangkok, Thailand</footnote>

<footnote n="90">⁹⁰Médica Sur Clinic & Foundation, Mexico City, Mexico</footnote>

<footnote n="91">⁹¹Liver Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA</footnote>

<footnote n="92">⁹²European Association for the Study of the Liver (EASL) International Liver Foundation, Geneva, Switzerland</footnote>

<footnote n="93">⁹³Department of Medicine, University of Otago, Wellington, New Zealand</footnote>

<footnote n="94">⁹⁴School of Medicine, Federal University of Bahia, Salvador, Brazil</footnote>

<footnote n="95">⁹⁵School of Medicine, University of Palermo, Palermo, Italy</footnote>

<footnote n="96">⁹⁶Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqués de Valdecilla University Hospital, Santander, Spain</footnote>

<footnote n="97">⁹⁷Faculty of Medicine, University of Kelaniya, Kelaniya, Sri Lanka</footnote>

<footnote n="98">⁹⁸Washington University School of Medicine, St. Louis, MO 63110, USA</footnote>

<footnote n="99">⁹⁹Erasmus MC University Medical Center, Rotterdam, the Netherlands</footnote>

<footnote n="10">¹⁰CHU Bordeaux, Bordeaux, France</footnote>

<footnote n="101">¹⁰¹Department of Hepatology & Gastroenterology, Charité - Universitätsmedizin Berlin, Berlin, Germany</footnote>

<footnote n="102">¹⁰²St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia</footnote>

<footnote n="103">¹⁰³Digestive Diseases Department, Hospital General Universitario de Valencia, Valencia, Spain</footnote>

<footnote n="104">¹⁰⁴Banner Liver Support Group, Phoenix, AZ, USA</footnote>

<footnote n="105">¹⁰⁵Department of Family Medicine, University of Washington, Seattle, WA, USA</footnote>

<footnote n="106">¹⁰⁶Liver Unit, Hospital Privado de Rosario, Rosario, Argentina</footnote>

<footnote n="107">¹⁰⁷Centre des Maladies Digestives Lausanne, Lausanne, Switzerland</footnote>

<footnote n="108">¹⁰⁸Fourth Department of Internal Medicine, First Faculty of Medicine, Charles University, Prague, Czech Republic</footnote>

<footnote n="109">¹⁰⁹Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden</footnote>

<footnote n="110">¹¹⁰Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt</footnote>

<footnote n="111">¹¹¹Department of Surgery, Faculty of Medicine, National Ribat University, Khartoum, Sudan</footnote>

<footnote n="112">¹¹²Tropical Medicine Department, Ain Shams University, Cairo, Egypt</footnote>

<footnote n="113">¹¹³Fatty Liver Foundation, Boise, ID, USA</footnote>

<footnote n="114">¹¹⁴Storr Liver Centre, Westmead Hospital, Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia</footnote>

<footnote n="115">¹¹⁵Endemic Medicine Department, Cairo University, Cairo, Egypt</footnote>

<footnote n="116">¹¹⁶Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai, China</footnote>

<footnote n="117">¹¹⁷Federal University of Sao Paulo, São Paulo, Brazil</footnote>

<footnote n="118">¹¹⁸Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland</footnote>

<footnote n="119">¹¹⁹Faculty of Medicine, Minia University, Minya, Egypt</footnote>

<footnote n="120">¹²⁰Central Virginia VA Health Care System and Virginia Commonwealth University, Richmond, VA, USA</footnote>

<footnote n="121">¹²¹Liver Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina</footnote>

<footnote n="122">¹²²Institute of Clinical Physiology, National Research Council, Pisa, Italy</footnote>

<footnote n="123">¹²³Department of Gastroenterology & Hepatology, University Hospital Ghent, Ghent, Belgium</footnote>

<footnote n="124">¹²⁴Division of Hepatology, University Hospital Wuerzburg, Wuerzburg, Germany</footnote>

<footnote n="125">¹²⁵Beatty Liver and Obesity Center, Inova Health System, Falls Church, VA, USA</footnote>

<footnote n="126">¹²⁶Nikomed Medical Centre, Yerevan, Armenia</footnote>

<footnote n="127">¹²⁷Carol Davila University of Medicine and Pharmacy, Bucharest, Romania</footnote>

<footnote n="128">¹²⁸Independent participant, Myrtle Beach, SC, USA</footnote>

<footnote n="129">¹²⁹Departamento de Gastroenterologia, Hospital de Clínicas, Universidade Nacional de Asunción, San Lorenzo, Paraguay</footnote>

<footnote n="130">¹³⁰Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore</footnote>

<footnote n="131">¹³¹Division of Gastroenterology and Hepatology, Geneva University Hospital, Geneva, Switzerland</footnote>

<footnote n="132">¹³²Liver Unit, Hospital Clínic, FCRB-IDIBAPS, University of Barcelona, Barcelona, Spain</footnote>

<footnote n="133">¹³³Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark</footnote>

<footnote n="134">¹³⁴Department of Medicine, Aga Khan University, Karachi, Pakistan</footnote>

<footnote n="135">¹³⁵British Liver Trust, Winchester, UK</footnote>

<footnote n="136">¹³⁶Department of Nutrition and Dietetics, Princess Alexandra Hospital, Brisbane, Queensland, Australia</footnote>

<footnote n="137">¹³⁷Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia</footnote>

<footnote n="138">¹³⁸Medical Care Center for Gastroenterology Bayerischer Platz, Berlin, Germany</footnote>

<footnote n="139">¹³⁹Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey</footnote>

<footnote n="140">¹⁴⁰Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA</footnote>

<footnote n="141">¹⁴¹Department of Gastroenterology & Hepatology, Federal Research Centre of Nutrition, Biotechnology & Food Safety, Moscow, Russia</footnote>

<footnote n="142">¹⁴²King Fahd Hospital of the University, Al-Khobar, and College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia</footnote>

<footnote n="143">¹⁴³Department of Transplantation and Surgery, Kuwait University, Kuwait City, Kuwait</footnote>

<footnote n="144">¹⁴⁴Newcastle University, Newcastle, UK</footnote>

<footnote n="145">¹⁴⁵Geneva University Hospital, Geneva, Switzerland</footnote>

<footnote n="146">¹⁴⁶National Academy of Medical Sciences, Kathmandu, Nepal</footnote>

<footnote n="147">¹⁴⁷Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan</footnote>

<footnote n="148">¹⁴⁸Emory University School of Medicine, Atlanta, GA, USA</footnote>

<footnote n="149">¹⁴⁹Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan</footnote>

<footnote n="150">¹⁵⁰School of Human Movement and Nutrition Sciences, The University of Queensland, Brisbane, Queensland, Australia</footnote>

<footnote n="151">¹⁵¹Department of Public Health, Jordan University of Science and Technology, Irbid, Jordan</footnote>

<footnote n="152">¹⁵²Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea</footnote>

<footnote n="153">¹⁵³Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea</footnote>

<footnote n="154">¹⁵⁴Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA</footnote>

<footnote n="155">¹⁵⁵Maastricht University Medical Center, Maastricht, the Netherlands</footnote>

<footnote n="156">¹⁵⁶Institut Pasteur de Bangui, Bangui, Central African Republic</footnote>

<footnote n="157">¹⁵⁷Center for Global Health, Istituto Superiore Di Sanità (ISS), UniCamillus-Saint Camillus International University of Health Sciences, Rome, Italy</footnote>

<footnote n="158">¹⁵⁸Department of Pediatric Gastroenterology, Emma's Children Hospital, Amsterdam University Medical Center, Amsterdam, the Netherlands</footnote>

<footnote n="159">¹⁵⁹Department of Liver Patients' Association, Brussels, Belgium</footnote>

<footnote n="160">¹⁶⁰Nature Reviews Gastroenterology & Hepatology, Berlin, Germany</footnote>

<footnote n="161">¹⁶¹Cyprus Liver Patients Association, Nicosia, Cyprus</footnote>

<footnote n="162">¹⁶²Department of Pediatrics, Denver Health Medical Center, Denver, CO, USA</footnote>

<footnote n="163">¹⁶³South Denver Gastroenterology, Englewood, CO, USA</footnote>

<footnote n="164">¹⁶⁴Gastroenterology "A" Department, Rabta University Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia</footnote>

<footnote n="165">¹⁶⁵Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland</footnote>

<footnote n="166">¹⁶⁶Department of Pediatrics, Columbia University, New York, NY, USA</footnote>

<footnote n="167">¹⁶⁷Urban Health Collaborative, Dornsife School of Public Health, Drexel University, Philadelphia, PA, USA</footnote>

<footnote n="168">¹⁶⁸Department of Internal Medicine, University Hospital Clementino Fraga Filho, School of Medicine, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil</footnote>

<footnote n="169">¹⁶⁹Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan</footnote>

<footnote n="170">¹⁷⁰Novo Nordisk A/S, Vandtårnsvæj 108-110, 2860 Søborg, Denmark</footnote>

<footnote n="171">¹⁷¹Masira Research Institute, Medical School, Universidad de Santander (UDES), Bucaramanga, Colombia</footnote>

<footnote n="172">¹⁷²Cayetano Heredia Peruvian University, Lima, Peru</footnote>

<footnote n="173">¹⁷³INOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisbon, Portugal</footnote>

<footnote n="174">¹⁷⁴Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran</footnote>

<footnote n="175">¹⁷⁵Alma Mater-University of Bologna, Bologna, Italy</footnote>

<footnote n="176">¹⁷⁶GLI, Lakewood, NJ, USA</footnote>

<footnote n="177">¹⁷⁷University Hospital "St Ivan Rilski", Medical University of Sofia, Sofia, Bulgaria</footnote>

<footnote n="178">¹⁷⁸CIC bioGUNE, Technology Park of Bizkaia, Derio, Spain</footnote>

<footnote n="179">¹⁷⁹Service of Hepatology and Gastroenterology, Department of Internal Medicine, University Clinics of Kinshasa, Kinshasa, Democratic Republic of the Congo</footnote>

<footnote n="180">¹⁸⁰Mid-Atlantic Permanente Medical Group, Rockville, MD, USA</footnote>