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AGING 2021, Vol. 13, No. 1
Research Paper

The burden of liver cirrhosis and underlying etiologies: results fromthe global burden of disease study 2017
Mimi Zhai1,*, Jianhai Long2,*, Sushun Liu3, Chun Liu3, Li Li3, Leping Yang3, Yamin Li1,4, Bo Shu3
1

Xiangya Nursing School, Central South University, Changsha, Hunan 410013, China
Department of Respiratory, Beijing Tiantan Hospital, Capital Medicine University, Beijing 100050, China
3
Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan
410011, China
4
Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha,
Hunan 410011, China*Equal contribution
2

Correspondence to: Bo Shu, Yamin Li; email: shubo3@csu.edu.cn, aminny@csu.edu.cn
Keywords: liver cirrhosis, etiology, global burden of disease study
Received: April 29, 2020
Accepted: September 19, 2020
Published: January 12, 2021
Copyright: © 2021 Zhai et al. This is an open access article distributed under the terms of the Creative Commons Attribution
License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original
author and source are credited.

ABSTRACT
Background: To evaluate the pattern and prevalence trends of liver cirrhosis caused by specific etiologies.
Results: Globally, the number of prevalent cases increased 74.53% from 1990 to 2017. The ASR increased 0.75
per year. The most pronounced increases were found in middle-high and high socio-demographic index (SDI)
regions, especially in the Caribbean and Latin America. Among the etiologies, non-alcoholic steatohepatitis(NASH) related liver cirrhosis accounted for 59.46% of the cases. The ASR increased 1.74 per year, and theincrease was observed in all 5 SDI regions. In addition, the ASR of liver cirrhosis caused by alcohol also
increased in both sexes and all SDI regions. In contrast, the ASR of liver cirrhosis caused by hepatitis B virus(HBV) and hepatitis C virus (HCV) decreased, especially in middle and low-middle SDI regions.
Conclusions: Though the number of people suffering from HBV and HCV decreases, liver cirrhosis is still a major
threat to health. Additionally, the number of people with cirrhosis caused by alcohol and NASH continues togrow. Thus, more targeted and specific strategies should be established based on etiology and prevalence
trends of liver cirrhosis.
Methods: We collected data based on Global Burden of Disease (GBD) 2017 study. The age standardized
prevalence rate (ASR) and estimated annual percentage changes (EAPC) were used to estimate the trends inprevalence by population, etiologies and regions.

lowest, with a value of 12.1% [2]. Moreover, newly
diagnosed cases continue to increase globally in the lastfew decades, although many public health initiatives
have been implemented.

INTRODUCTION
Liver cirrhosis is a major health issue that afflicted
more than 160 million people in 2017 worldwide [1].
Previous studies have documented that the incidence ofliver cirrhosis varies, and chronic viral hepatitis is themost common cause, especially hepatitis B virus (HBV)
and hepatitis C virus (HCV) [2, 3]. The highest
incidence of liver cirrhosis is found in East Asia. In
contrast, the incidence in Southern Latin America is the

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The major causative agents of liver cirrhosis include
HBV, HCV, alcohol use, non-alcoholic steatohepatitis(NASH) and other causes [4]. The etiologies of livercirrhosis in each region or country varies bases on the
different risk factors. For instance, HBV is the main

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cause of liver cirrhosis in China [5]. In Mexico, Japanand the United States, liver cirrhosis is mainly caused by
HCV. Moreover, the number of patients with cirrhosis
caused by alcohol and NASH is continuously increasing.
Thus, more targeted prevention strategies should be
implemented based on the trends in liver cirrhosis.

data, researchers can extensively investigate the trends
and landscape of liver cirrhosis throughout the world.
Bosetti et al. studied the worldwide mortality ofcirrhosis in 2002, and de Carvalho et al. described theburden of liver cirrhosis in Brazil in 2017 [2, 4].
Additionally, a recent study mainly demonstrated thetrend of liver cirrhosis mortality worldwide. It indicatedthat hepatitis was the main causes of cirrhosis, but the
impact caused by hepatitis might be attenuated andovertaken by NASH in future [6]. However, rare studies

The Global Burden of Disease (GBD) study provides
estimates of the liver cirrhosis burden in 195 countries
and territories. By using the latest GBD 2017 study

Figure 1. The worldwide prevalence cases of liver cirrhosis in 195 countries and territories. (A) The worldwide prevalence cases ofliver cirrhosis in 1990. (B) The worldwide prevalence cases of liver cirrhosis in 2017.

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Figure 2. The global burden of liver cirrhosis in 195 countries and territories. (A) The ASR of liver cirrhosis in 1990. (B) The ASR ofliver cirrhosis in 2017. (C) The EAPC of liver cirrhosis from 1990 to 2017.

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have investigated the landscape of liver cirrhosis
worldwide via the newest GBD data. In addition, none
study has analyzed the relationship between
sociological indicators and cirrhosis. In this study, weused GBD data to evaluate detailed information on livercirrhosis. We also investigated the burden of livercirrhosis by using the prevalence of various etiologies
and overall liver cirrhosis prevalence.

prevalent cases increased in all 21 regions (Figure 4A).
Country with the largest number of liver cirrhosis cases
was East Asia, followed by South Asia and Southeast
Asia (Figure 4B). The highest ASR in 2017 was also
found in East Asia (Figure 4C and Supplementary Table
7). Additionally, the fastest increase in ASR was found in
the Caribbean (Supplementary Table 7). In contrast, thefastest decrease in ASR was found in Western SubSaharan Africa, with an EAPC of -0.63 (95% CI -0.72-0.55) (Supplementary Table 7).

RESULTSFor etiologies of liver cirrhosis, NASH was the main
etiology with 0.89 billion prevalent patients (59.46%
of liver cirrhosis cases). A total of 0.43 billion prevalent
cases were infected with HBV (28.72%) (Figure 5A
and Supplementary Table 7). Additionally, the fastest
increase in ASR was also found in patients with NASH
(EAPC=1.74 95% CI 1.73-1.75). Contrarily, The ASR
decreased in patients infected with HBV and HCV from1990 to 2017 (Supplementary Table 7).

Global liver cirrhosis burden
Globally, the prevalent cases increased 74.53%.
Although, China had the largest number of patients in1990 (0.27 billion) and in 2017 (0.42 billion) (Figure 1A,
1B and Supplementary Table 6), the growth rate wasonly 54.88%. The United Arab Emirates (UAE) had thehighest growth rate with a value of 837.26% (Figure 1B
and Supplementary Table 6). The worldwide ASR was
19640.0 per 100000 in 2017 (Figure 2A, 2B and
Supplementary Table 7). Among all the countries, thehighest ASR was found in Egypt, followed by Qatar andUnited Arab Emirates (Figure 2A, 2B). The worldwide
ASR increase 0.75 per year (95% CI 0.73-0.77) (Figure
2C and Supplementary Table 7), and the fastest increase
was found in Oman, followed by Iran, Saint Vincent and
the Grenadines (Figure 2C). Contrarily, 40 of the 195
countries and territories demonstrated a decrease trend in
ASR, and the fastest reduction was observed in
Mozambique (Figure 2C).

The influential factors for EAPC
A significant relationship was studied between EAPC
and ASR, HDI, respectively. The ASR of livercirrhosis could be considered the disease reservoir
at baseline. Additionally, the HDI could be considered
the level of available medical resources. In or study,
the EAPC was negatively correlated with the ASR
in 1990 (r=-0.548, p<0.001) (Figure 5B). In contrast,
the EAPC was positively correlated with the HDI in2017 (r=0.628, p<0.001) (Figure 5B). The results
demonstrated that countries with higher HDI
have suffered a more rapid increase in ASR ofliver cirrhosis.

The prevalence cases increased in all 5 SDI regions,especially in the middle-high SDI regions (Figure 3 andSupplementary Table 7). For geographical regions, theFigure 3. The analysis of liver cirrhosis and its etiologies. The liver cirrhosis cases caused by different etiologies, by SDI regions.

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Figure 4. The analysis of liver cirrhosis at a regional level. (A) The prevalence cases of liver cirrhosis caused by different etiologies indifferent region and sex. (B) The prevalence cases of liver cirrhosis in different regions. (C) The ASR of liver cirrhosis in different regions.

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1.74 per year (95% CI 1.73-1.75) (Supplementary Table1). The fastest increase in ASR was found in Oman
(Supplementary Figure 2C). Among all the countries,
193 of them demonstrated an increase trend in ASR;
Afghanistan and Nigeria did not. The ASR also
increased in all 5 SDI regions, especially in the middle
and middle-high SDI regions (Supplementary Table 1).
For the geographical regions, the prevalent cases andthe ASR both increased in all 21 regions(Supplementary Figure 2C and Supplementary Table 1).
In addition, the fastest increase in ASR was observed inWestern Sub-Saharan Africa (Supplementary Table 1).

Liver cirrhosis due to NASH
Globally, approximately 59.46% of patients with livercirrhosis had NASH in 2017 (Figure 5A and
Supplementary Table 7). The prevalent cases increased
125.61% from 1990 to 2017 (Supplementary Table 1).
The country with the largest number of NASH-induced
liver cirrhosis patients was China, and its growth rate
was 117.89% (Supplementary Figure 1A, 1B and
Supplementary Table 6). The highest ASR was
observed in Qatar in 1990 and in UAE in 2017
(Supplementary Figure 2A, 2B). The ASR increased

Figure 5. (A) Composition ratio of each etiology in prevalence cases of liver cirrhosis in 1990 and 2017. (B) The correlation between EAPC
and ASR in 1990, HDI in 2017.

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(Supplementary Figure 8C). Additionally, the ASR
increased in all 5 SDI regions (Supplementary Table 4).
The ASR also increased in all of the geographical regions
except for Asia Pacific–high income, Western SubSaharan Africa and Southern Sub-Saharan Africa(Supplementary Figure 8C, Supplementary Table 4).

Liver cirrhosis due to hepatitis B
The prevalent cases of liver cirrhosis caused by hepatitis
B increased 29.16% during the period (Supplementary
Table 2). Globally, approximately 28.72% of patientswith prevalent liver cirrhosis had HBV in 2017 (Figure
5A). China had the largest number of patients in theworld (Supplementary Figure 3A, 3B). Qatar had thelargest increase with a growth rate of 568.30%(Supplementary Figure 3B and Supplementary Table 6).
The highest ASR was found in Sierra Leone(Supplementary Figure 4A, 4B). Additionally, the ASRof liver cirrhosis caused by HBV displayed a minor
decrease with an EAPC of -0.39 (95% CI -0.46--0.34)(Supplementary Table 2). The highest EAPC was foundin Taiwan. In contrast, the lowest EAPC was observedin Mexico. The ASR decreased in all 5 SDI regions,especially in the Middle SDI regions (Supplementary
Table 2). For the geographical regions, the ASR also
decreased in all 21 regions (Supplementary Figure 4C
and Supplementary Table 2).

Liver cirrhosis due to other causes
The prevalence of liver cirrhosis caused by other causes
increased 45.30% from 1990 to 2017 (Supplementary
Table 5). Although China also had the largest number ofpatients related to the other causes, the growth rate was
4.10%. The highest growth rate was found in Qatar, witha value of 409.68%, and the lowest growth rate wasfound in Bosnia and Herzegovina (Supplementary Figure
9A, 9B and Supplementary Table 6). The highest ASR
was observed in South Korea and Brunei (Supplementary
Figure 10A, 10B). Additionally, the global ASR
remained stable during this period with an EAPC of 0.04
(95% CI -0.02-0.10) (Supplementary Figure 10C andSupplementary Table 5). The ASR increased in the low
and low-middle regions. For geographical regions, theASR decreased in 7 regions, including Asia Pacific–highincome, East Asia, Central Europe, etc. (Supplementary
Figure 10C and Supplementary Table 5).

Liver cirrhosis due to hepatitis C
The prevalence of liver cirrhosis caused by HCV
increased 28.74% (Supplementary Table 3). China also
had the largest number of HCV patients in the world(Supplementary Figure 5A, 5B). The UAE had the fastest
increase rate in the number of HCV patients(Supplementary Figure 5B and Supplementary Table 6).
The highest ASR was observed in Egypt (Supplementary
Figure 6A, 6B). Similar to the liver cirrhosis caused by
HBV, the ASR of HCV-related liver cirrhosis displayed adecrease trend with an EAPC of -0.39 (95% CI -0.42-0.36) (Supplementary Table 3). The fastest ASR increase
was found in Iran, and the fastest ASR decrease wasfound in Equatorial Guinea (Supplementary Figure 6C).
Additionally, the ASR also decreased in all 5 SDI
regions. Amazing, the ASR increased in Eastern Europe
and North America–high income regions (Supplementary
Figure 6C and Supplementary Table 3).

DISCUSSION
The worldwide prevalence of liver cirrhosis continues
increase [7]. The heterogeneous pattern in risk factors isdifferent [8, 9]. Although the incidence of HBV and
HCV continuously decreases, the ever-increasing
incidence of liver cirrhosis caused by alcohol and
NASH remains a formidable threat [10, 11].
In our study, we analyzed the trends of liver cirrhosis. In
general, the prevalence of liver cirrhosis continuously
increased. The trends were mainly dominated by anincrease of NASH-induced liver cirrhosis, with a smaller
contribution from alcohol use. The prevalent cases of
HBV and HCV increased during the period, but the ASR
decreased [12]. The decrease trends of HBV and HCV
ASR were mainly caused by the decrease in the numberof patients with HBV- and HCV-related liver cirrhosis[13, 14]. In contrast to the previous result that hepatitis
was the main cause of liver cirrhosis in the prevalent
cases, liver cirrhosis caused by NASH occupied a major
position [12]. Consequently, exploring the exact pattern ofliver cirrhosis etiologies was important for developing
specific preventive measures. Additionally, the HDI and
EAPC were found to be positively correlated in our study.
HDI was a summary measure indicative of a long andhealthy life, being knowledgeable and having a decent
standard of living. The HDI simplified and captured only
part of human development details. Moreover, patients

Liver cirrhosis due to alcohol use
The prevalence of liver cirrhosis caused by alcoholincreased 78.27% (Supplementary Table 4). China also
had the largest number of patients related to alcohol use in
the world (Supplementary Figure 7A, 7B). The UAE had
the highest increase of the number of cirrhosis patients
caused by alcohol with a growth rate of 863.93%(Supplementary Figure 7B and Supplementary Table 6).
Hungary and Slovakia had the highest ASR in 1990 andin 2017, respectively (Supplementary Figure 8A, 8B).
Globally, the ASR increased 0.84 (95% CI 0.79-0.89)
per year. With respect to the individual countries, thefastest increase of ASR was observed in Vietnam

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with liver cirrhosis had a long survival time. With theincrease in the life expectancy index, the prevalence of
patients with liver cirrhosis also increased. Thus, thedimensions of HDI might be positively correlated with
EAPC. Moreover, a study conducted by Liu et al. also
indicated that the HDI and EAPC were positively
correlated in patients with liver cancer [1]. In 1990 and2017, 46% and 59% of liver cirrhosis patients,
respectively, had NASH. The fastest ASR increase inprevalent cases was also found in patients with NASH,
which was different from the results found in other studies[1, 15]. Additionally, in contrast to other studies that used
incidence as an indicator, we used prevalence as theindicator. Because patients with liver cirrhosis had a longsurvival time, it was more reasonable to use prevalence as
the indicator. In addition, we further analyzed the reason
why NASH accounts for the highest proportion inprevalent cases. By analyzing the GBD data, we foundthat liver cirrhosis caused by hepatitis accounted for thehighest proportion of deaths, while liver cirrhosis causedby NASH accounted for the lowest proportion of deaths.
Therefore, more and more patients had cirrhosis causedby NASH over time, but fewer patients died, resulting in ahigher proportion of prevalent cases. A study revealed thatthe annual percentage change of mortality of NASHinduced cirrhosis was 3-fold greater than that for alcoholinduced cirrhosis, and NASH surpassed alcohol andhepatitis to be the leading cause of liver cirrhosis in the
United States [16]. This might be related to the obesity
epidemic in the United States, and the burden of NASHinduced liver cirrhosis might increase over the next
decade [17]. Thus, public policy, which focused on
primary prevention, prompt diagnosis, and pre-emptive
therapy should establish plans to raise awareness anddecrease the disease burden of NASH.

Asia. This finding indicates that more effective public
measures to prevent HBV should be implemented in thesecountries [23]. Moreover, the development of anti-HBV
drugs, such as entecavir and tenofovir, has further reduced
the number of patients [24]. Thus, we can expect that the
number of patients with liver cirrhosis caused by HBVwill be significantly decreased in the future.
Similar to liver cirrhosis caused by HBV, the ASR ofliver cirrhosis caused by HCV also decreased.
Additionally, the ASR of liver cirrhosis caused by HCV
also decreased in all 5 SDI regions. To our surprise, the
ASR increased in Eastern Europe, Tropical Latin
America and North America–high income, which was
not the same as the results reported in the study
conducted by The Polaris Observatory HCVCollaborators [25]. China also had the largest number ofpatients with HCV, but the growth rate was 34.01% [26].
This might be related to a lack of effective treatment
measures before 2014. Subsequently, direct-acting
antiviral therapy was introduced, and more than 90% of
patients with all genotypes of HCV could be cured [27].
As a result, interventions should be introduced all over
the world, such as promoting direct-acting antiviraltherapy and reducing the therapy price.
Alcohol was proven to be a major risk factor for livercirrhosis. The ASR of liver cirrhosis caused by alcohol
use increased from 1990 to 2017. The results obtained by
Asrani et al. also revealed that alcohol use and NASH
had overtaken hepatitis as the primary causes of liverdiseases in Western countries [28]. The increase in ASR
was higher in females than in males, similar to the result
obtained by Roerecke et al. [29]. Additionally, alcohol
was found to play an increasingly important role inchronic liver diseases [30]. Thus, polices to reduce
alcohol consumption should be implemented, and people
with high alcohol consumption should receive
interventions to reduce their intake [29].

HBV was an important risk factor for liver cirrhosis insome regions [6, 18]. Moreover, HBV infection
contributed to half of the mortality associated with livercancer [19]. In our study, we found that liver cirrhosis
caused by HBV was more prevalent in the low-middle
and middle SDI regions. Additionally, more than 50% of
patients with liver cirrhosis in Africa were caused by
HBV, and nearly 40% of the cases in East Asia, Central
Asia and Oceania were also caused by HBV. By
promoting HBV vaccination, the ASR of the 21 regions
decreased over the last few decades. Although China had
the largest number of HBV patients, the growth rate wasonly 10.21% from 1990 to 2017. This was mainly due tothe promotion of HBV vaccines in China [20]. By
implementing these measures, the number of patients
suffering from HBV infection was significantly
suppressed in the general population [21, 22]. Amazingly,
although the ASR decreased during the period in all 5 SDI
regions, the slowest decrease was found in high the SDI
regions, such as North America–high income and South

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Although the GBD data demonstrated the temporal
trend in the prevalence of liver cirrhosis, several
limitations should be noted. The accuracy of
results obtained from GBD data depend on the quality
and quantity of liver cirrhosis data. In some countries orregions, the liver cirrhosis data were incomplete oreven missing. This might lead to an underestimation of
the severity of liver cirrhosis. Additionally, we could
only study the temporal trend in the prevalence ofliver cirrhosis by each etiology, and the interaction
between etiologies could not be studied via the GBD
data. Moreover, the GBD data of liver cirrhosis was notclassified by decompensation and compensation.
Thus, we could not discuss the difference between
compensated and decompensated cirrhosis in termsof epidemiology.

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In summary, liver cirrhosis poses a huge threat topeople's health. Although the ASR of liver cirrhosis
caused by hepatitis decreased with HBV vaccinationand direct-acting antiviral therapy, the ASR of livercirrhosis caused by alcohol and NASH continued to
grow during the study period. Thus, public healthpriorities that target alcohol consumption and NASH
should be implemented as soon as possible.

HCV: hepatitis C virus; HDI: human development
index; NASH: non-alcoholic steatohepatitis; SDI: sociodemographic index.

AUTHOR CONTRIBUTIONS
Study design: Zhai MM, Long JH, Li YM and Shu B.
Data collection: Zhai MM, Long JH, Li YM and Shu B.
Data analysis: Liu SS and Liu C. Figures: Li L.
Manuscript writing: Long JH, Li L, Yang LP and
Liu SS. Manuscript proofing: Long JH, Zhai MM, Li
YM and Bo Shu.

MATERIALS AND METHODS
Study data

ACKNOWLEDGMENTS

Detailed information on liver cirrhosis was obtained
from the GBD 2017 study. By using thesociodemographic index (SDI), the 195 countries andterritories in the GBD 2017 study were divided into 5groups. The 195 countries and territories were grouped
into 21 regions according to their geographical location.
The method of extracting data and the estimation
method of liver cirrhosis disease burden were based on
the Liu et al. study [1]. Moreover, we collected andanalyzed the human development index (HDI) andmatched the HDI with the GBD data.

We are indebted to individuals who have participated inthis study or have helped with this article.

CONFLICTS OF INTEREST
The authors declare no conflicts of interest.

FUNDING
This study was supported by Chen Xiaoping Scienceand Technology Development Foundation (CXPJJH
11900001-2019334), Hunan Provincial Natural Science
Foundation of China (No. 2018JJ3715).

Statistical analysis
To study the trend in prevalence from 1990 to 2017, theage-standardized prevalence rate (ASR) and theestimated annual percentage change (EAPC) were used
[1, 31]. The calculation of ASR and EAPC have beendetailed in Liu et al. study [1]. By analyzing the ASR,
we determined the prevalence of the disease andchanges in etiology. Moreover, the ASR provided atheoretical basis for establishing targeted preventive
strategies for public health departments [32]. In ourstudy, EAPC was used to assess the trend in the ASR
over a period of time [32, 33]. If ASR was a trend ofincrease, the value of EAPC and the lower boundary of
95% confidence interval (CI) are both greater than 0. In
contrast, if ASR was a trend of decrease, the value of
EAPC and the upper boundary of 95% CI are bothless than 0. Additionally, if ASR was a constant trend,
the 95% CI of EAPC contains 0. Additionally, acorrelation analysis was conducted to study the
influential factors for EAPC. All data were analyzed by
R software (R 3.5.1 software, Institute for Statistics andMathematics) and STATA (STATA 13.1, StataCorp
LLC). A p-value less than 0.05 was considered
statistically significant.

REFERENCES

Abbreviations
ASR: Age standardized prevalence rate; CI: confidence
interval; EAPC: estimated annual percentage changes;
GBD: Global burden of disease; HBV: hepatitis B virus;

www.aging-us.com

287

1.

Liu Z, Jiang Y, Yuan H, Fang Q, Cai N, Suo C, Jin L,
Zhang T, Chen X. The trends in incidence of primaryliver cancer caused by specific etiologies: results fromthe global burden of disease study 2016 andimplications for liver cancer prevention. J Hepatol.
2019; 70:674–83.
https://doi.org/10.1016/j.jhep.2018.12.001
PMID:30543829

2.

de Carvalho JR, Villela-Nogueira CA, Perez RM,
Portugal FB, Flor LS, Campos MR, Schramm JM.
Burden of chronic viral hepatitis and liver cirrhosis in
Brazil - the Brazilian global burden of disease study.
Ann Hepatol. 2017.
https://doi.org/10.5604/01.3001.0010.5280
PMID:29055917

3.

Westbrook RH, Dusheiko G. Natural history of hepatitis
C. J Hepatol. 2014; 61:S58–68.
https://doi.org/10.1016/j.jhep.2014.07.012
PMID:25443346

4.

Bosetti C, Levi F, Lucchini F, Zatonski WA, Negri E, La
Vecchia C. Worldwide mortality from cirrhosis: an
update to 2002. J Hepatol. 2007; 46:827–39.
https://doi.org/10.1016/j.jhep.2007.01.025

AGING

PMID:17336419
5.

Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ.
Estimations of worldwide prevalence of chronic
hepatitis B virus infection: a systematic review of data
published between 1965 and 2013. Lancet. 2015;
386:1546–55.
https://doi.org/10.1016/S0140-6736(15)61412-X
PMID:26231459

6.

GBD 2017 Cirrhosis Collaborators. The global, regional,
and national burden of cirrhosis by cause in 195
countries and territories, 1990-2017: a systematic
analysis for the global burden of disease study 2017.
Lancet Gastroenterol Hepatol. 2020; 5:245–66.
https://doi.org/10.1016/S2468-1253(19)30349-8
PMID:31981519

7.

14. Mendy ME, Welzel T, Lesi OA, Hainaut P, Hall AJ,
Kuniholm MH, McConkey S, Goedert JJ, Kaye S,
Rowland-Jones S, Whittle H, Kirk GD. Hepatitis B viralload and risk for liver cirrhosis and hepatocellular
carcinoma in the Gambia, West Africa. J Viral Hepat.
2010; 17:115–22.
https://doi.org/10.1111/j.1365-2893.2009.01168.x
PMID:19874478
15. Cotter TG, Charlton MR. The triumph of bacchus: theemergence of nonalcoholic steatohepatitis andalcoholic liver disease as the leading causes ofmortality from cirrhosis. Hepatology. 2019; 69:931–33.
https://doi.org/10.1002/hep.30408 PMID:30570159
16. Kim D, Li AA, Perumpail BJ, Gadiparthi C, Kim W,
Cholankeril G, Glenn JS, Harrison SA, Younossi ZM,
Ahmed A. Changing trends in etiology-based andethnicity-based annual mortality rates of cirrhosis andhepatocellular carcinoma in the United States.
Hepatology. 2019; 69:1064–74.
https://doi.org/10.1002/hep.30161 PMID:30014489

Nault JC, Ningarhari M, Rebouissou S, Zucman-Rossi J.
The role of telomeres and telomerase in cirrhosis andliver cancer. Nat Rev Gastroenterol Hepatol. 2019;16:544–58.
https://doi.org/10.1038/s41575-019-0165-3
PMID:31253940

8.

Wang X, Wu B. Critical issues in the diagnosis andtreatment of liver cirrhosis. Gastroenterol Rep (Oxf).
2019; 7:227–230.
https://doi.org/10.1093/gastro/goz024
PMID:31413829

9.

Costa FO, Lages EJ, Lages EM, Cota LO. Periodontitis inindividuals with liver cirrhosis: a case-control study. J
Clin Periodontol. 2019; 46:991–98.
https://doi.org/10.1111/jcpe.13172 PMID:31336404

17. Younossi ZM, Stepanova M, Afendy M, Fang Y,
Younossi Y, Mir H, Srishord M. Changes in theprevalence of the most common causes of chronic liverdiseases in the United States from 1988 to 2008. Clin
Gastroenterol Hepatol. 2011; 9:524–30.e1.
https://doi.org/10.1016/j.cgh.2011.03.020
PMID:21440669
18. Höner Zu Siederdissen C, Cornberg M. Management of
HBV and HBV/HDV-associated liver cirrhosis. Visc Med.
2016; 32:86–94.
https://doi.org/10.1159/000445518
PMID:27413725

10. Tapper EB, Parikh ND. Mortality due to cirrhosis andliver cancer in the United States, 1999-2016:
observational study. BMJ. 2018; 362:k2817.
https://doi.org/10.1136/bmj.k2817
PMID:30021785

19. Global Burden of Disease Study 2013 Collaborators.
Global, regional, and national incidence, prevalence,and years lived with disability for 301 acute andchronic diseases and injuries in 188 countries, 19902013: a systematic analysis for the global burden of
disease study 2013. Lancet. 2015; 386:743–800.
https://doi.org/10.1016/S0140-6736(15)60692-4
PMID:26063472

11. GBD 2016 Alcohol Collaborators. Alcohol use andburden for 195 countries and territories, 1990-2016: asystematic analysis for the global burden of disease
study 2016. Lancet. 2018; 392:1015–35.
https://doi.org/10.1016/S0140-6736(18)31310-2
PMID:30146330

20. Jia Y, Li L, Cui F, Zhang D, Zhang G, Wang F, Gong X,
Zheng H, Wu Z, Miao N, Sun X, Zhang L, Lv J, Yang F.
Cost-effectiveness analysis of a hepatitis B vaccination
catch-up program among children in shandong province,
China. Hum Vaccin Immunother. 2014; 10:2983–91.
https://doi.org/10.4161/hv.29944 PMID:25483678

12. Wang X, Lin SX, Tao J, Wei XQ, Liu YT, Chen YM, Wu B.
Study of liver cirrhosis over ten consecutive years inSouthern China. World J Gastroenterol. 2014;
20:13546–55.
https://doi.org/10.3748/wjg.v20.i37.13546
PMID:25309085

21. Huang P, Zhu LG, Zhu YF, Yue M, Su J, Zhu FC, Yang HT,
Zhang Y, Shen HB, Yu RB, Zhai XJ, Peng ZH.
Seroepidemiology of hepatitis B virus infection andimpact of vaccination. World J Gastroenterol. 2015;
21:7842–50.
https://doi.org/10.3748/wjg.v21.i25.7842
PMID:26167084

13. Vento S, Dzudzor B, Cainelli F, Tachi K. Liver cirrhosis in
sub-Saharan Africa: neglected, yet important. Lancet
Glob Health. 2018; 6:e1060–61.
https://doi.org/10.1016/S2214-109X(18)30344-9
PMID:30219314

www.aging-us.com

288

AGING

22. Luo Z, Li L, Ruan B. Impact of the implementation of a
vaccination strategy on hepatitis B virus infections in
China over a 20-year period. Int J Infect Dis. 2012;
16:e82–88.
https://doi.org/10.1016/j.ijid.2011.10.009
PMID:22178658

28. Asrani SK, Devarbhavi H, Eaton J, Kamath PS. Burdenof liver diseases in the world. J Hepatol. 2019;70:151–71.
https://doi.org/10.1016/j.jhep.2018.09.014
PMID:30266282
29. Roerecke M, Vafaei A, Hasan OS, Chrystoja BR, Cruz
M, Lee R, Neuman MG, Rehm J. Alcohol
consumption and risk of liver cirrhosis: a systematic
review and meta-analysis. Am J Gastroenterol. 2019;
114:1574–86.
https://doi.org/10.14309/ajg.0000000000000340
PMID:31464740

23. Hahné SJ, De Melker HE, Kretzschmar M, Mollema L,
Van Der Klis FR, Van Der Sande MA, Boot HJ.
Prevalence of hepatitis B virus infection in the
Netherlands in 1996 and 2007. Epidemiol Infect. 2012;
140:1469–80.
https://doi.org/10.1017/S095026881100224X
PMID:22078095

30. Singh SP, Panigrahi S, Mishra D, Khatua CR. Alcoholassociated liver disease, not hepatitis B, is the major
cause of cirrhosis in Asia. J Hepatol. 2019; 70:1031–32.
https://doi.org/10.1016/j.jhep.2019.01.003
PMID:30782425

24. Choi J, Lim YS. Comparison of risk of hepatocellular
carcinoma between tenofovir and entecavir: One
direction or no direction. J Hepatol. 2019; 71:846–847.
https://doi.org/10.1016/j.jhep.2019.06.013
PMID:31351769

31. Hankey BF, Ries LA, Kosary CL, Feuer EJ, Merrill RM,
Clegg LX, Edwards BK. Partitioning linear trends inage-adjusted rates. Cancer Causes Control. 2000;
11:31–35.
https://doi.org/10.1023/a:1008953201688
PMID:10680727

25. Polaris Observatory HCVC. Global prevalence andgenotype distribution of hepatitis C virus infection in
2015: a modelling study. Lancet Gastroenterol Hepatol.
2017; 2:161–176.
https://doi.org/10.1016/S2468-1253(16)30181-9
26. Liu Z, Yang Q, Shi O, Ye W, Chen X, Zhang T. The
epidemiology of hepatitis B and hepatitis C infections in
China from 2004 to 2014: an observational populationbased study. J Viral Hepat. 2018; 25:1543–54.
https://doi.org/10.1111/jvh.12938
PMID:29851287

32. Hung GY, Horng JL, Yen HJ, Lee CY, Lin LY. Changing
incidence patterns of hepatocellular carcinoma amongage groups in Taiwan. J Hepatol. 2015; 63:1390–6.
https://doi.org/10.1016/j.jhep.2015.07.032
PMID:26256438
33. Gao S, Yang WS, Bray F, Va P, Zhang W, Gao J, Xiang
YB. Declining rates of hepatocellular carcinoma inurban shanghai: incidence trends in 1976-2005. Eur J
Epidemiol. 2012; 27:39–46.
https://doi.org/10.1007/s10654-011-9636-8
PMID:22160277

27. Pawlotsky JM, Feld JJ, Zeuzem S, Hoofnagle JH. From
non-A, non-B hepatitis to hepatitis C virus cure. J
Hepatol. 2015; 62:S87–99.
https://doi.org/10.1016/j.jhep.2015.02.006
PMID:25920094

www.aging-us.com

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SUPPLEMENTARY MATERIALSSupplementary Figures

Supplementary Figure 1. The worldwide prevalence cases of liver cirrhosis caused by HBV in countries. (A) The worldwide
prevalence cases of liver cirrhosis caused by HBV in 1990. (B) The worldwide prevalence cases of liver cirrhosis caused by HBV in 2017.

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Supplementary Figure 2. The global burden of liver cirrhosis caused by HBV in countries. (A) The ASR of liver cirrhosis caused by
HBV in 1990. (B) The ASR of liver cirrhosis caused by HBV in 2017. (C) The EAPC of liver cirrhosis caused by HBV from 1990 to 2017.

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Supplementary Figure 3. The worldwide prevalence cases of liver cirrhosis caused by HCV in countries. (A) The worldwide
prevalence cases of liver cirrhosis caused by HCV in 1990. (B) The worldwide prevalence cases of liver cirrhosis caused by HCV in 2017.

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Supplementary Figure 4. The global burden of liver cirrhosis caused by HCV in countries. (A) The ASR of liver cirrhosis caused by
HCV in 1990. (B) The ASR of liver cirrhosis caused by HCV in 2017. (C) The EAPC of liver cirrhosis caused by HCV from 1990 to 2017.

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Supplementary Figure 5. The worldwide prevalence cases of liver cirrhosis caused by alcohol use in countries. (A) The
worldwide prevalence cases of liver cirrhosis caused by alcohol use in 1990. (B) The worldwide prevalence cases of liver cirrhosis caused byalcohol use in 2017.

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Supplementary Figure 6. The global burden of liver cirrhosis caused by alcohol use in countries. (A) The ASR of liver cirrhosis
caused by alcohol use in 1990. (B) The ASR of liver cirrhosis caused by alcohol use in 2017. (C) The EAPC of liver cirrhosis caused by alcohol
use from 1990 to 2017.

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Supplementary Figure 7. The worldwide prevalence cases of liver cirrhosis caused by NASH in countries. (A) The worldwide
prevalence cases of liver cirrhosis caused by NASH in 1990. (B) The worldwide prevalence cases of liver cirrhosis caused by NASH in 2017.

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Supplementary Figure 8. The global burden of liver cirrhosis caused by NASH in countries. (A) The ASR of liver cirrhosis caused by
NASH in 1990. (B) The ASR of liver cirrhosis caused by NASH in 2017. (C) The EAPC of liver cirrhosis caused by NASH from 1990 to 2017.

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Supplementary Figure 9. The worldwide prevalence cases of liver cirrhosis caused by other causes in countries. (A) The
worldwide prevalence cases of liver cirrhosis caused by other causes in 1990. (B) The worldwide prevalence cases of liver cirrhosis caused byother causes in 2017.

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Supplementary Figure 10. The global burden of liver cirrhosis caused by other causes in countries. (A) The ASR of liver cirrhosis
caused by other causes in 1990. (B) The ASR of liver cirrhosis caused by other causes in 2017. (C) The EAPC of liver cirrhosis caused by othercauses from 1990 to 2017.

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Supplementary Tables
Please browse Full Text version to see the data of Supplementary Tables 1 to 7.

Supplementary Table 1. The prevalence cases, age-standardized prevalence, and temporal trend of liver cirrhosis
caused by NASH.
Supplementary Table 2. The prevalence cases, age-standardized prevalence, and temporal trend of liver cirrhosis
caused by HBV.
Supplementary Table 3. The prevalence cases, age-standardized prevalence, and temporal trend of liver cirrhosis
caused by HCV.
Supplementary Table 4. The prevalence cases, age-standardized prevalence, and temporal trend of liver cirrhosis
caused by alcohol use.
Supplementary Table 5. The prevalence cases, age-standardized prevalence, and temporal trend of liver cirrhosis
caused by other causes.
Supplementary Table 6. The prevalence cases and temporal trend of liver cirrhosis caused by each etiology in 195
countries and territories.
Supplementary Table 7. The prevalence cases, age-standardized prevalence, and temporal trend of liver cirrhosis.

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