tbuckley/cabot-search huggingface dataset:
DNDI-6174 is a preclinical candidate for visceral leishmaniasis that targets the cytochrome bc <sub>1</sub>
Authors: Stéphanie Braillard, Martine Keenan, Karen J. Breese, Jacob Heppell, Michael Abbott, Rafiqul Islam, David M. Shackleford, Kasiram Katneni, Elly Crighton, Gong Chen, Rahul Patil, Given Lee, Karen L. White, Sandra Carvalho, Richard J. Wall, Giulia Chemi, Fabio Zuccotto, Silvia González, Maria Marco, Julianna Deakyne, David Standing, Gino Brunori, Jonathan J. Lyon, Pablo Castañeda-Casado, Isabel Camino, Maria S. Martinez Martinez, Bilal Zulfiqar, Vicky M. Avery, Pim-Bart Feijens, Natascha Van Pelt, An Matheeussen, Sarah Hendrickx, Louis Maes, Guy Caljon, Vanessa Yardley, Susan Wyllie, Susan A. Charman, Eric Chatelain
Journal: Science Translational Medicine (2023)

New drugs for visceral leishmaniasis that are safe, low cost, and adapted to the field are urgently required. Despite concerted efforts over the last several years, the number of new chemical entities that are suitable for clinical development for the treatment of Leishmania remains low. Here, we describe the discovery and preclinical development of DNDI-6174, an inhibitor of Leishmania cytochrome bc 1 complex activity that originated from a phenotypically identified pyrrolopyrimidine series. This compound fulfills all target candidate profile criteria required for progression into preclinical development. In addition to good metabolic stability and pharmacokinetic properties, DNDI-6174 demonstrates potent in vitro activity against a variety of Leishmania species and can reduce parasite burden in animal models of infection, with the potential to approach sterile cure. No major flags were identified in preliminary safety studies, including an exploratory 14-day toxicology study in the rat. DNDI-6174 is a cytochrome bc 1 complex inhibitor with acceptable development properties to enter preclinical development for visceral leishmaniasis.
Data-driven science and diversity in the All of Us Research Program
Authors: Geoffrey S. Ginsburg, Joshua C. Denny, Sheri D. Schully
Journal: Science Translational Medicine (2023)

The National Institutes of Health’s All of Us Research Program is an accessible platform that hosts genomic and phenotypic data to be collected from 1 million participants in the United States. Its mission is to accelerate medical research and clinical breakthroughs with a special emphasis on diversity.
Association of county-level socioeconomic status with meningioma incidence and outcomes
Authors: Sangami Pugazenthi, Mackenzie Price, Rodrigo De La Vega Gomar, Carol Kruchko, Kristin A Waite, Jill S Barnholtz-Sloan, Kyle M Walsh, Albert H Kim, Quinn T Ostrom
Journal: Neuro-Oncology (2023)

Abstract Background Prior literature suggests that individual socioeconomic status (SES) may influence incidence, treatments, and survival of brain tumor cases. We aim to conduct the first national study to evaluate the association between US county-level SES and incidence, treatment, and survival in meningioma. Methods The Central Brain Tumor Registry of the United States analytic dataset, which combines data from CDC’s National Program of Cancer Registries (NPCR) and National Cancer Institute's Surveillance, Epidemiology, and End Results Program, was used to identify meningioma cases from 2006 to 2019. SES quintiles were created using American Community Survey data. Logistic regression models were used to evaluate associations between SES and meningioma. Cox proportional hazard models were constructed to assess the effect of SES on survival using the NPCR analytic dataset. Results A total of 409 681 meningioma cases were identified. Meningioma incidence increased with higher county-level SES with Q5 (highest quintile) having a 12% higher incidence than Q1 (incidence rate ratios (IRR) = 1.12, 95%CI: 1.10–1.14; P &amp;lt; .0001). The Hispanic group was the only racial–ethnic group that had lower SES associated with increased meningioma incidence (Q5: age-adjusted incidence ratio (AAIR) = 9.02, 95%CI: 8.87–9.17 vs. Q1: AAIR = 9.33, 95%CI: 9.08–9.59; IRR = 0.97, 95%CI: 0.94–1.00; P = .0409). Increased likelihood of surgical treatment was associated with Asian or Pacific Islander non-Hispanic individuals (compared to White non-Hispanic (WNH)) (OR = 1.28, 95%CI: 1.23–1.33, P &amp;lt; .001) and males (OR = 1.31, 95%CI: 1.29–1.33, P &amp;lt; .001). Black non-Hispanic individuals (OR = 0.90, 95%CI: 0.88–0.92, P &amp;lt; .001) and those residing in metropolitan areas (OR = 0.96, 95%CI: 0.96–0.96, P &amp;lt; .001) were less likely to receive surgical treatment compared to WNH individuals. Overall median survival was 137 months, and survival was higher in higher SES counties (Q5 median survival = 142 months). Conclusions Higher county-level SES was associated with increased meningioma incidence, surgical treatment, and overall survival. Racial–ethnic stratification identified potential disparities within the meningioma population. Further work is needed to understand the underpinnings of socioeconomic and racial disparities for meningioma patients.
Maternal serum concentrations of per- and polyfluoroalkyl substances and childhood acute lymphoblastic leukemia
Authors: Rena R Jones, Jessica M Madrigal, Rebecca Troisi, Heljä-Marja Surcel, Hanna Öhman, Juha Kivelä, Hannu Kiviranta, Panu Rantakokko, Jani Koponen, Danielle N Medgyesi, Katherine A McGlynn, Joshua Sampson, Paul S Albert, Mary H Ward
Journal: JNCI Journal of the National Cancer Institute (2023)

Per- and polyfluoroalkyl substances (PFAS) are widespread and environmentally persistent chemicals with immunotoxic properties. Children are prenatally exposed through maternal transfer of PFAS to cord blood, but no studies have investigated the relationship with childhood leukemia.
Current and Evolving Multimodality Cardiac Imaging in Managing Transthyretin Amyloid Cardiomyopathy
Authors: Louhai Alwan, Dominik C. Benz, Sarah A.M. Cuddy, Stephan Dobner, Isaac Shiri, Federico Caobelli, Benedikt Bernhard, Simon F. Stämpfli, Franz Eberli, Mauricio Reyes, Raymond Y. Kwong, Rodney H. Falk, Sharmila Dorbala, Christoph Gräni
Journal: JACC. Cardiovascular imaging (2023)
A Phenomapping Tool and Clinical Score to Identify Low Diuretic Efficiency in Acute Decompensated Heart Failure
Authors: Matthew W. Segar, Muhammad Shahzeb Khan, Kershaw V. Patel, Javed Butler, Ashwin K. Ravichandran, Mary Norine Walsh, DuWayne Willett, Gregg C. Fonarow, Mark H. Drazner, Robert J. Mentz, Jennifer Hall, Maryjane A. Farr, S. Susan Hedayati, Clyde Yancy, Larry A. Allen, W.H. Wilson Tang, Ambarish Pandey
Journal: JACC Heart Failure (2023)
Echocardiographic Outcomes With Transcatheter Edge-to-Edge Repair for Degenerative Mitral Regurgitation in Prohibitive Surgical Risk Patients
Authors: Leo Marcoff, Konstantinos Koulogiannis, Lilian Aldaia, Anuj Mediratta, Scott M. Chadderdon, Moody M. Makar, Tobias Friedrich Ruf, Theresa Gößler, Jonathan G. Zaroff, Gordon K. Leung, Ivy A. Ku, Michael Nabauer, Paul A. Grayburn, Zuyue Wang, Katie M. Hawthorne, Dale E. Fowler, Jacob P. Dal-Bianco, Mani A. Vannan, Carmine Bevilacqua, Massimiliano Meineri, Joerg Ender, Anna Flo Forner, Jyothy J. Puthumana, Atizazul Hassan Mansoor, Dustin J. Lloyd, Steven J. Voskanian, Andrew Ghobrial, Rebecca T. Hahn, Feroze Mahmood, Christiane Haeffele, Geraldine Ong, Leonhard Moritz Schneider, Dee Dee Wang, Nishant K. Sekaran, Elana Koss, Priti Mehla, Serge Harb, Rhonda Miyasaka, Maria Ivannikova, Terri Stewart-Dehner, Lucas Mitchel, Sasan R. Raissi, Daniel Kalbacher, Santanu Biswas, Edwin C. Ho, Ythan Goldberg, Robert L. Smith, Jörg Hausleiter, D. Scott Lim, Linda D. Gillam
Journal: JACC. Cardiovascular imaging (2023)
Left Ventricular Ejection Fraction and the Future of Heart Failure Phenotyping
Authors: Matthew G. Dimond, Nasrien E. Ibrahim, Mona Fiuzat, John J.V. McMurray, JoAnn Lindenfeld, Tariq Ahmad, Biykem Bozkurt, Michael R. Bristow, Javed Butler, Peter E. Carson, G. Michael Felker, Mariell Jessup, Jaime Murillo, Toru Kondo, Scott D. Solomon, William T. Abraham, Christopher M. O’Connor, Mitchell A. Psotka
Journal: JACC Heart Failure (2023)

Heart failure (HF) is a complex syndrome traditionally classified by left ventricular ejection fraction (LVEF) cutpoints. Although LVEF is prognostic for risk of events and predictive of response to some HF therapies, LVEF is a continuous variable and cutpoints are arbitrary, often based on historical clinical trial enrichment decisions rather than physiology. Holistic evaluation of the treatment effects for therapies throughout the LVEF range suggests the standard categorization paradigm for HF merits modification. The multidisciplinary Heart Failure Collaboratory reviewed data from large-scale HF clinical trials and found that many HF therapies have demonstrated therapeutic benefit across a large range of LVEF, but specific treatment effects vary across that range. Therefore, HF should practically be classified by association with an LVEF that is reduced or not reduced, while acknowledging uncertainty around the precise LVEF cutpoint, and future research should evaluate new therapies across the continuum of LVEF.
Prognostic Interplay Between Exercise Capacity and PET-Derived Myocardial Flow Reserve
Authors: Ahmed Ibrahim Ahmed, Mahmoud Al Rifai, Fares Alahdab, Moath Said Alfawara, Yushui Han, Malek Nayfeh, John J. Mahmarian, Faisal Nabi, Ahmed Soliman, Kershaw Patel, William A. Zoghbi, Mouaz H. Al-Mallah
Journal: JACC. Cardiovascular imaging (2023)
Protein biomarkers and alternatively methylated cell-free DNA detect early stage pancreatic cancer
Authors: Roni Ben-Ami, Qiao-Li Wang, Jinming Zhang, Julianna G Supplee, Johannes F Fahrmann, Roni Lehmann-Werman, Lauren K Brais, Jonathan Nowak, Chen Yuan, Maureen Loftus, Ana Babic, Ehsan Irajizad, Tal Davidi, Aviad Zick, Ayala Hubert, Daniel Neiman, Sheina Piyanzin, Ofer Gal-Rosenberg, Amit Horn, Ruth Shemer, Benjamin Glaser, Natalia Boos, Kunal Jajoo, Linda Lee, Thomas E Clancy, Douglas A Rubinson, Kimmie Ng, John A Chabot, Fay Kastrinos, Michael Kluger, Andrew J Aguirre, Pasi A Jänne, Nabeel Bardeesy, Ben Stanger, Mark H O'Hara, Jacob Till, Anirban Maitra, Erica L Carpenter, Andrea J Bullock, Jeanine Genkinger, Samir M Hanash, Cloud P Paweletz, Yuval Dor, Brian M Wolpin
Journal: Gut (2023)

Objective Pancreatic ductal adenocarcinoma (PDAC) is commonly diagnosed at an advanced stage. Liquid biopsy approaches may facilitate detection of early stage PDAC when curative treatments can be employed. Design To assess circulating marker discrimination in training, testing and validation patient cohorts (total n=426 patients), plasma markers were measured among PDAC cases and patients with chronic pancreatitis, colorectal cancer (CRC), and healthy controls. Using CA19-9 as an anchor marker, measurements were made of two protein markers (TIMP1, LRG1) and cell-free DNA (cfDNA) pancreas-specific methylation at 9 loci encompassing 61 CpG sites. Results Comparative methylome analysis identified nine loci that were differentially methylated in exocrine pancreas DNA. In the training set (n=124 patients), cfDNA methylation markers distinguished PDAC from healthy and CRC controls. In the testing set of 86 early stage PDAC and 86 matched healthy controls, CA19-9 had an area under the receiver operating characteristic curve (AUC) of 0.88 (95% CI 0.83 to 0.94), which was increased by adding TIMP1 (AUC 0.92; 95% CI 0.88 to 0.96; p=0.06), LRG1 (AUC 0.92; 95% CI 0.88 to 0.96; p=0.02) or exocrine pancreas-specific cfDNA methylation markers at nine loci (AUC 0.92; 95% CI 0.88 to 0.96; p=0.02). In the validation set of 40 early stage PDAC and 40 matched healthy controls, a combined panel including CA19-9, TIMP1 and a 9-loci cfDNA methylation panel had greater discrimination (AUC 0.86, 95% CI 0.77 to 0.95) than CA19-9 alone (AUC 0.82; 95% CI 0.72 to 0.92). Conclusion A combined panel of circulating markers including proteins and methylated cfDNA increased discrimination compared with CA19-9 alone for early stage PDAC.
Targeting MMP9 in CTNNB1 mutant hepatocellular carcinoma restores CD8<sup>+</sup>T cell-mediated antitumour immunity and improves anti-PD-1 efficacy
Authors: Ning Cai, Kun Cheng, Yue Ma, Sha Liu, Ran Tao, Yani Li, Danfeng Li, Bin Guo, Wenlong Jia, Huifang Liang, Jianping Zhao, Limin Xia, Ze-yang Ding, Jinhong Chen, Wanguang Zhang
Journal: Gut (2023)

Objective The gain of function (GOF) CTNNB1 mutations (CTNNB1 GOF ) in hepatocellular carcinoma (HCC) cause significant immune escape and resistance to anti-PD-1. Here, we aimed to investigate the mechanism of CTNNB1 GOF HCC-mediated immune escape and raise a new therapeutic strategy to enhance anti-PD-1 efficacy in HCC. Design RNA sequencing was performed to identify the key downstream genes of CTNNB1 GOF associated with immune escape. An in vitro coculture system, murine subcutaneous or orthotopic models, spontaneously tumourigenic models in conditional gene-knock-out mice and flow cytometry were used to explore the biological function of matrix metallopeptidase 9 (MMP9) in tumour progression and immune escape. Single-cell RNA sequencing and proteomics were used to gain insight into the underlying mechanisms of MMP9. Results MMP9 was significantly upregulated in CTNNB1 GOF HCC. MMP9 suppressed infiltration and cytotoxicity of CD8 + T cells, which was critical for CTNNB1 GOF to drive the suppressive tumour immune microenvironment (TIME) and anti-PD-1 resistance. Mechanistically, CTNNB1 GOF downregulated sirtuin 2 (SIRT2), resulting in promotion of β-catenin/lysine demethylase 4D (KDM4D) complex formation that fostered the transcriptional activation of MMP9. The secretion of MMP9 from HCC mediated slingshot protein phosphatase 1 (SSH1) shedding from CD8 + T cells, leading to the inhibition of C-X-C motif chemokine receptor 3 (CXCR3)-mediated intracellular of G protein-coupled receptors signalling. Additionally, MMP9 blockade remodelled the TIME and potentiated the sensitivity of anti-PD-1 therapy in HCC. Conclusions CTNNB1 GOF induces a suppressive TIME by activating secretion of MMP9. Targeting MMP9 reshapes TIME and potentiates anti-PD-1 efficacy in CTNNB1 GOF HCC.
Performance of the European Kidney Function Consortium (EKFC) creatinine-based equation in United States cohorts
Authors: Pierre Delanaye, Andrew D. Rule, Elke Schaeffner, Etienne Cavalier, Junyan Shi, Andrew N. Hoofnagle, Ulf Nyman, Jonas Björk, Hans Pottel
Journal: Kidney International (2023)

Estimating glomerular filtration rate (GFR) is important in daily practice to assess kidney function and adapting the best clinical care of patients with and without chronic kidney disease. The new creatinine-based European Kidney Function Consortium (EKFC) equation is used to estimate GFR. This equation was developed and validated mainly in European individuals and based on a rescaled creatinine, with the rescaling factor (Q-value) defined as the median normal value of serum creatinine in a given population. The validation was limited in Non-Black Americans and absent in Black Americans. Here, our cross-sectional analysis included 12,854 participants from nine studies encompassing large numbers of both non-Black and Black Americans with measured GFR by clearance of an exogenous marker (reference method), serum creatinine, age, sex, and self-reported race available. Two strategies were considered with population-specific Q-values in Black and non-Black men and women (EKFC
A population-based cohort defined risk of hyperkalemia after initiating SGLT-2 inhibitors, GLP1 receptor agonists or DPP-4 inhibitors to patients with chronic kidney disease and type 2 diabetes
Authors: Edouard L. Fu, Julianna Mastrorilli, Katsiaryna Bykov, Deborah J. Wexler, Alexander Cervone, Kueiyu Joshua Lin, Elisabetta Patorno, Julie M. Paik
Journal: Kidney International (2023)

Hyperkalemia is a common adverse event in patients with chronic kidney disease (CKD) and type 2 diabetes and limits the use of guideline-recommended therapies such as renin-angiotensin system inhibitors. Here, we evaluated the comparative effects of sodium-glucose cotransporter-2 inhibitors (SGLT-2i), glucagon-like peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i) on the risk of hyperkalemia. We conducted a population-based active-comparator, new-user cohort study using claims data from Medicare and two large United States commercial insurance databases (April 2013-April 2022). People with CKD stages 3-4 and type 2 diabetes who newly initiated SGLT-2i vs. DPP-4i (141671 patients), GLP-1RA vs. DPP-4i (159545 patients) and SGLT-2i vs. GLP-1RA (93033 patients) were included. The primary outcome was hyperkalemia diagnosed in inpatient or outpatient settings. Secondary outcomes included hyperkalemia diagnosed in inpatient or emergency department setting, and serum potassium levels of 5.5 mmol/L or more. Pooled hazard ratios and rate differences were estimated after propensity score matching to adjust for over 140 potential confounders. Initiation of SGLT-2i was associated with a lower risk of hyperkalemia compared with DPP-4i (hazard ratio 0.74; 95% confidence interval 0.68-0.80) and contrasted to GLP-1RA (0.92; 0.86-0.99). Compared with DPP-4i, GLP-1RA were also associated with a lower risk of hyperkalemia (0.80; 0.75-0.86). Corresponding absolute rate differences/1000 person-years were -24.8 (95% confidence interval -31.8 to -17.7), -5.0 (-10.9 to 0.8), and -17.7 (-23.4 to -12.1), respectively. Similar findings were observed for the secondary outcomes, among subgroups, and across single agents within the SGLT-2i and GLP-1RA classes. Thus, SGLT-2i and GLP-1RA are associated with a lower risk of hyperkalemia than DPP-4i in patients with CKD and type 2 diabetes, further supporting the use of these drugs in this population.
Persistence of post-COVID symptoms in the general population two years after SARS-CoV-2 infection: A systematic review and meta-analysis
Authors: Cesar Fernandez-de-las-Peñas, Kin Israel Notarte, Raymart Macasaet, Jacqueline Veronica Velasco, Jesus Alfonso Catahay, Abbygail Therese Ver, William Chung, Juan A. Valera-Calero, Marcos Navarro-Santana
Journal: Journal of Infection (2023)

This meta-analysis investigated the prevalence of post-COVID symptoms two-years after SARS-CoV-2 infection.
Portable hypothermic oxygenated machine perfusion for organ preservation in liver transplantation: A randomized, open-label, clinical trial
Authors: Guergana G. Panayotova, Keri E. Lunsford, R. Cutler Quillin, Abbas Rana, Vatche G. Agopian, Grace S. Lee-Riddle, Daniela Markovic, Flavio Paterno, Adam D. Griesemer, Arpit Amin, Diane Alonso, Juan P. Rocca, Daniel Borja-Cacho, Roberto Hernandez-Alejandro, John J. Fung, Shawn J. Pelletier, Shimul A. Shah, James V. Guarrera
Journal: Hepatology (2023)

Background and Aims: In liver transplantation, cold preservation induces ischemia, resulting in significant reperfusion injury. Hypothermic oxygenated machine perfusion (HMP-O 2 ) has shown benefits compared to static cold storage (SCS) by limiting ischemia-reperfusion injury. This study reports outcomes using a novel portable HMP-O 2 device in the first US randomized control trial. Approach and Results: The PILOT trial (NCT03484455) was a multicenter, randomized, open-label, noninferiority trial, with participants randomized to HMP-O 2 or SCS. HMP-O 2 livers were preserved using the Lifeport Liver Transporter and Vasosol perfusion solution. The primary outcome was early allograft dysfunction. Noninferiority margin was 7.5%. From April 3, 2019, to July 12, 2022, 179 patients were randomized to HMP-O 2 (n=90) or SCS (n=89). The per-protocol cohort included 63 HMP-O 2 and 73 SCS. Early allograft dysfunction occurred in 11.1% HMP-O 2 (N=7) and 16.4% SCS (N=12). The risk difference between HMP-O 2 and SCS was −5.33% (one-sided 95% upper confidence limit of 5.81%), establishing noninferiority. The risk of graft failure as predicted by Liver Graft Assessment Following Transplant score at seven days (L-GrAFT 7 ) was lower with HMP-O 2 [median (IQR) 3.4% (2.4–6.5) vs. 4.5% (2.9–9.4), p =0.024]. Primary nonfunction occurred in 2.2% of all SCS (n=3, p =0.10). Biliary strictures occurred in 16.4% SCS (n=12) and 6.3% (n=4) HMP-O 2 ( p =0.18). Nonanastomotic biliary strictures occurred only in SCS (n=4). Conclusions: HMP-O 2 demonstrates safety and noninferior efficacy for liver graft preservation in comparison to SCS. Early allograft failure by L-GrAFT 7 was lower in HMP-O 2 , suggesting improved early clinical function. Recipients of HMP-O 2 livers also demonstrated a lower incidence of primary nonfunction and biliary strictures, although this difference did not reach significance.
Integrative Multi-omics Analysis Reveals Different Metabolic Phenotypes Based on Molecular Characteristics in Thyroid Cancer
Authors: Yoo Hyung Kim, Sang Jun Yoon, Mina Kim, Hwan Hee Kim, Young Shin Song, Jin Woo Jung, Dohyun Han, Sun Wook Cho, Sung Won Kwon, Young Joo Park
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Thyroid cancer metabolic characteristics vary depending on the molecular subtype determined by mutational status. We aimed to investigate the molecular subtype-specific metabolic characteristics of thyroid cancers. Experimental Design: An integrative multi-omics analysis was conducted, incorporating transcriptomics, metabolomics, and proteomics data obtained from human tissues representing distinct molecular characteristics of thyroid cancers: BRAF-like (papillary thyroid cancer with BRAFV600E mutation; PTC-B), RAS-like (follicular thyroid cancer with RAS mutation; FTC-R), and ATC-like (anaplastic thyroid cancer with BRAFV600E or RAS mutation; ATC-B or ATC-R). To validate our findings, we employed tissue microarray of human thyroid cancer tissues and performed in vitro analyses of cancer cell phenotypes and metabolomic assays after inducing genetic knockdown. Results: Metabolic properties differed between differentiated thyroid cancers of PTC-B and FTC-R, but were similar in dedifferentiated thyroid cancers of ATC-B/R, regardless of their mutational status. Tricarboxylic acid (TCA) intermediates and branched-chain amino acids (BCAA) were enriched with the activation of TCA cycle only in FTC-R, whereas one-carbon metabolism and pyrimidine metabolism increased in both PTC-B and FTC-R and to a great extent in ATC-B/R. However, the protein expression levels of the BCAA transporter (SLC7A5) and a key enzyme in one-carbon metabolism (SHMT2) increased in all thyroid cancers and were particularly high in ATC-B/R. Knockdown of SLC7A5 or SHMT2 inhibited the migration and proliferation of thyroid cancer cell lines differently, depending on the mutational status. Conclusions: These findings define the metabolic properties of each molecular subtype of thyroid cancers and identify metabolic vulnerabilities, providing a rationale for therapies targeting its altered metabolic pathways in advanced thyroid cancer.
Defining an approach for therapeutic strategies in metabolic dysfunction–associated steatotic liver disease after liver transplantation
Authors: Mohammad Shadab Siddiqui, Mark Muthiah, Sanjaya K. Satapathy, Kavish R. Patidar, Mamatha Bhat, Danielle Brandman, Kymberly D. Watt, Mary Rinella
Journal: Hepatology (2023)

Occurrence of metabolic dysfunction–associated steatotic liver disease (MASLD) is common following liver transplantation (LT). MASLD can be classified as a recurrent disease when it occurs in patients receiving LT for metabolic dysfunction–associated steatohepatitis (MASH) or as de novo when it occurs in patients undergoing transplantation for non-metabolic dysfunction–associated steatohepatitis etiologies of liver disease. Fibrosis progression in patients with MASLD is accelerated, with progression to cirrhosis occurring more rapidly compared with the general (ie, non-LT) population. Moreover, the metabolic burden in LT recipients with MASLD is high and synergizes with liver disease to negatively affect the clinical course. Despite the oversized clinical burden of MASLD among LT recipients, there is currently a lack of regulatory approach and pathway for therapeutics development in this patient population. The present document, thus, provides guidance for therapeutics development that incorporates nuances of transplant care in patients with post-LT MASLD to facilitate drug development.