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"NASH"

Review

Prospects of late-stage development agents in the treatment of metabolic dysfunction-associated steatohepatitis
Brian Lee, Ussama Ghumman, Lisa D. Pedicone, Andres Gomez Aldana, Eric Lawitz
Clin Mol Hepatol 2025;31(4):1167-1196.
Published online August 4, 2025
DOI: https://doi.org/10.3350/cmh.2025.0337
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a spectrum of pathology involving fatty liver disease that may progress to fibrosis, cirrhosis, hepatocellular carcinoma, and liver failure. The prevalence of MASLD and metabolic dysfunction-associated steatohepatitis (MASH) continues to increase, mirroring the rise in global prevalence of related comorbidities such as obesity and type 2 diabetes mellitus. Due to the alarming rise of these comorbidities, a greater proportion of the population is at risk for developing MASLD and MASH. As such, there has been a significant effort to develop effective therapies for MASLD and MASH. Recently, the U.S. Food and Drug Administration approved resmetirom, a selective thyroid hormone receptor-beta agonist, as the first treatment for patients with MASH. In India, the Drug Controller General of India approved saroglitazar, a dual peroxisome proliferator-activated receptor (PPAR) α/γ agonist, for the treatment of MASLD. Currently, we have various drug classes, including liver-specific therapies, in Phase 3 development with even more agents earlier in the pipeline. This review will discuss prospective therapies in later stages of development such as thyroid hormone receptor-beta agonists, PPAR agonists, glucagon-like peptide-1 receptor agonists, fibroblast growth factor 21 agonists, and fatty acid synthase inhibitors.

Citations

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  • Combination therapies for metabolic dysfunction-associated steatohepatitis: challenges and opportunities
    Xiao-Dong Zhou, Qiong-Yue Fan, Christopher D Byrne, Giovanni Targher, Mark D Muthiah, Daniel Q Huang, Qin-Fen Chen, Mazen Noureddin, Wenhao Li, Vlad Ratziu, Rohit Loomba, Sven M Francque, Arun J Sanyal, Ming-Hua Zheng
    Gut.2025; : gutjnl-2025-337431.     CrossRef
  • 5,359 View
  • 225 Download
  • 1 Web of Science
  • Crossref

Editorial

Steatotic liver disease

Screening strategies for non-alcoholic fatty liver disease: a holistic approach is needed
Philipp Kasper, Münevver Demir, Hans-Michael Steffen
Clin Mol Hepatol 2023;29(2):390-393.
Published online March 20, 2023
DOI: https://doi.org/10.3350/cmh.2023.0059

Citations

Citations to this article as recorded by  Crossref logo
  • GH Replacement Therapy Is Associated with Ameliorations in Body Composition and Fatty Liver Index in Patients with Adult-Onset Isolated GH Deficiency
    Elena Gangitano, Rebecca Rossetti, Giusy Simeone, Mariaignazia Curreli, Orietta Gandini, Stefania Mariani, Carla Lubrano
    Livers.2025; 5(4): 56.     CrossRef
  • Prognostic value of coronary artery calcium score for the prediction of atherosclerotic cardiovascular disease in participants with suspected nonalcoholic hepatic steatosis: Results from the multi-ethnic study of atherosclerosis
    Keishi Ichikawa, Spencer Hansen, Venkat S. Manubolu, Leili Pourafkari, Hooman Fazlalizadeh, Jairo Aldana-Bitar, Lisa B. VanWagner, Srikanth Krishnan, Matthew J. Budoff
    American Heart Journal.2023; 265: 104.     CrossRef
  • The Role of the Fatty Liver Index (FLI) in the Management of Non-Alcoholic Fatty Liver Disease: A Systematic Review
    Teodora Biciusca, Sorina Ionelia Stan, Mara Amalia Balteanu, Ramona Cioboata, Alice Elena Ghenea, Suzana Danoiu, Ana-Maria Bumbea, Viorel Biciusca
    Diagnostics.2023; 13(21): 3316.     CrossRef
  • 7,979 View
  • 69 Download
  • 3 Web of Science
  • Crossref

Reviews

Steatotic liver disease

Liver transplantation for non-alcoholic fatty liver disease: indications and post-transplant management
Sara Battistella, Francesca D’Arcangelo, Marco Grasso, Alberto Zanetto, Martina Gambato, Giacomo Germani, Marco Senzolo, Francesco Paolo Russo, Patrizia Burra
Clin Mol Hepatol 2023;29(Suppl):S286-S301.
Published online December 28, 2022
DOI: https://doi.org/10.3350/cmh.2022.0392
Non-alcoholic fatty liver disease (NAFLD) is currently the fastest growing indication to liver transplantation (LT) in Western Countries, both for end stage liver disease and hepatocellular carcinoma. NAFLD/non-alcoholic steatohepatitis (NASH) is often expression of a systemic metabolic syndrome; therefore, NAFLD/NASH patients require a multidisciplinary approach for a proper pre-surgical evaluation, which is important to achieve a post-transplant outcome comparable to that of other indications to LT. NAFLD/NASH patients are also at higher risk of post-transplant cardiovascular events, diabetes, dyslipidemia, obesity, renal impairment and recurrent NASH. Lifestyle modifications, included diet and physical activity, are key to improve survival and quality of life after transplantation. A tailored immunosuppressive regimen may be proposed in selected patients. Development of new drugs for the treatment of recurrent NASH is awaited.

Citations

Citations to this article as recorded by  Crossref logo
  • Examining the prevalence of hepatic steatosis and advanced fibrosis using non-invasive measures across Canada: A national estimate using the Canadian Health Measures Survey (CHMS) from 2009-2019
    Jacob Romano, Jessica Burnside, Giada Sebastiani, Alnoor Ramji, Keyur Patel, Mark Swain, Sahar Saeed
    Annals of Hepatology.2025; 30(1): 101757.     CrossRef
  • Macronutrient Modulation in Metabolic Dysfunction-Associated Steatotic Liver Disease—the Molecular Role of Fatty Acids compared with Sugars in Human Metabolism and Disease Progression
    Sinéad M Mullin, Aidan J Kelly, Méabh B Ní Chathail, Suzanne Norris, Christopher E Shannon, Helen M Roche
    Advances in Nutrition.2025; 16(3): 100375.     CrossRef
  • Metabolic Dysfunction-Associated Steatotic Liver Disease: Pathogenetic Links to Cardiovascular Risk
    Vlad Alexandru Ionescu, Gina Gheorghe, Nicolae Bacalbasa, Camelia Cristina Diaconu
    Biomolecules.2025; 15(2): 163.     CrossRef
  • Metabolic dysfunction-associated steatotic liver disease correlates with higher lower graft survival in liver transplant recipients with hepatocellular carcinoma
    Marwan Alsaqa, Leandro Sierra, Ana Marenco-Flores, Ximena Parraga, Romelia Barba, Daniela Goyes, N. Begum Ozturk, Michael P. Curry, Alan Bonder, Behnam Saberi
    European Journal of Gastroenterology & Hepatology.2025; 37(4): 497.     CrossRef
  • Clinical and Economic Burden of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in a Spanish Mediterranean Region: A Population-Based Study
    Javier Díaz Carnicero, Inma Saurí-Ferrer, Josep Redon, Jorge Navarro, Gonzalo Fernández, Carlos Hurtado, Karine Ferreira, Carolina Alvarez-Ortega, Antón Gómez, Carlos J. Martos-Rodríguez, David Martí-Aguado, Desamparados Escudero, Marta Cedenilla
    Journal of Clinical Medicine.2025; 14(7): 2441.     CrossRef
  • MASLD or MAFLD: fatty liver by any name will pose the same challenge
    Anil Chandra Anand, Dibyalochan Praharaj
    Metabolism and Target Organ Damage.2025;[Epub]     CrossRef
  • Cardiac Remodeling and Arrhythmic Burden in Pre-Transplant Cirrhotic Patients: Pathophysiological Mechanisms and Management Strategies
    Charilila-Loukia Ververeli, Yannis Dimitroglou, Stergios Soulaidopoulos, Evangelos Cholongitas, Constantina Aggeli, Konstantinos Tsioufis, Dimitris Tousoulis
    Biomedicines.2025; 13(4): 812.     CrossRef
  • Correspondence to letter to the editor on “Optimal tacrolimus levels for reducing CKD risk and the impact of intrapatient variability on CKD and ESRD development following liver transplantation”
    Soon Kyu Lee, Jong Young Choi
    Clinical and Molecular Hepatology.2025; 31(2): e212.     CrossRef
  • Risk Factors Related to the Development of Nonalcoholic Fatty Liver: A Systematic Review
    Omaira Valencia, Carolina López, Esteban Vanegas-Duarte, Carolina Fillizola, Diana Fernanda Bejarano Ramírez, Nicolás Andrés Cortés Mejía, Alonso Vera Torres, Kevork M. Peltekian
    Canadian Journal of Gastroenterology and Hepatology.2025;[Epub]     CrossRef
  • Safety, efficacy, and outcomes of invasive coronary angiography in liver transplant candidates
    Carme Ginard, Giulia Pagano, Salvatore Brugaletta, Annabel Blasi, Marta Sánchez-Ric, Ander Regueiro, Roger Pujol, Sergio Rodriguez-Tajes, Pablo Ruiz, Jordi Colmenero, Gonzalo Crespo
    JHEP Reports.2025; 7(7): 101428.     CrossRef
  • The Relationships Between MASLD, Extrahepatic Multimorbidity, and All-Cause Mortality in the UK Biobank Cohort
    Qi Feng, Chioma N Izzi-Engbeaya, Andrea D Branch, Benjamin H Mullish, Pinelopi Manousou, Mark Woodward
    The Journal of Clinical Endocrinology & Metabolism.2025; 111(1): e58.     CrossRef
  • MAFLD as a Cardiovascular Risk Factor: An Extended Retrospective Study with a Control Group
    Małgorzata Szymala-Pędzik, Marcin Piersiak, Maciej Pachana, Karolina Lindner-Pawłowicz, Wioletta Szczepaniak, Małgorzata Sobieszczańska
    Journal of Clinical Medicine.2025; 14(12): 4181.     CrossRef
  • Metabolic-associated fatty liver disease: Noninvasive diagnosis and assessment of liver fibrosis
    O. O. Karshina, I. S. Sabirov
    Meditsinskiy sovet = Medical Council.2025; (8): 72.     CrossRef
  • Are we standing on the shifting sands of post-transplant metabolic-associated steatotic liver disease?
    Renata Zatta, Luana S da Silva, Guilherme Felga, Carolina FMG Pimentel
    World Journal of Hepatology.2025;[Epub]     CrossRef
  • Corrected T1 (cT1) is the most appropriate diagnosis and monitoring tool for widespread adoption of resmetirom treatment in the United States
    Marika Hancock, Cayden Beyer, Michael Fuchs, Mukesh Harisinghani, Prasun Jalal, Michael Ndaa, Niharika Samala, Jose D. Vargas, Arjun Jayaswal
    Journal of Medical Economics.2025; 28(1): 1370.     CrossRef
  • Metabolic dysfunction-associated steatotic liver disease management in Saudi Arabia: A modified Delphi-based adaptation of international standards
    Faisal Abaalkhail, Faisal M. Sanai, Khalid AlSwat, Adnan Alzanbagi, Ahmed Aljedai, Ali Alshehri, Assim Alfadda, Hamdan Alghamdi, Majid Almadi, Mohammad Aleissa, Mona Ismail, Saud Alsifri, Turki Alzahrani, Saleh Alqahtani, Waleed Al Hamoudi
    Saudi Journal of Gastroenterology.2025;[Epub]     CrossRef
  • Integrated Genomic Analysis Reveals the Synergistic Role of PNPLA3 and ABCC8 Variants in Diabetic MASLD in Pakistan
    Asma Shabbir, Ambrina Khatoon, Zaigham Abbas, Sucheta Srivastava, Talat Mirza
    Medical Sciences.2025; 13(3): 178.     CrossRef
  • Sex-Stratified Prediction Models for 5-Year Nonalcoholic Fatty Liver Disease Risk in Thyroid Cancer Patients: A Nationwide Cohort Study
    Young Bin Cho, Kyoung Sik Park
    Biomedicines.2025; 13(9): 2250.     CrossRef
  • Genome-Based Mexican Diet Bioactives Target Molecular Pathways in HBV, HCV, and MASLD: A Bioinformatic Approach for Liver Disease Prevention
    Leonardo Leal-Mercado, Arturo Panduro, Alexis José-Abrego, Sonia Roman
    International Journal of Molecular Sciences.2025; 26(18): 8977.     CrossRef
  • Validation of MELD 3.0 and ReMELD-Na scoring systems: a German clinical cohort study
    Aghnia J. Putri, Decan Jiang, Zoltan Czigany, Arianeb Mehrabi, Markus Wolfgang Buechler, Uta Merle, Christoph Michalski, Peri Husen
    Langenbeck's Archives of Surgery.2025;[Epub]     CrossRef
  • How best to combine liver transplantation and bariatric surgery?—Results from a global, web‐based survey
    Jeannette Widmer, Janina Eden, Fariba Abbassi, Roberta Angelico, Fabian Rössler, Beat Müllhaupt, Philipp Dutkowski, Marco Bueter, Andrea Schlegel
    Liver International.2024; 44(2): 566.     CrossRef
  • Exploring the effects of epigallocatechin gallate on lipid metabolism in the rat steatotic liver during normothermic machine perfusion: Insights from lipidomics and RNA sequencing
    Shuxuan Li, Yao Zhi, Wentao Mu, Mingqian Li, Guoyue Lv
    European Journal of Pharmacology.2024; 964: 176300.     CrossRef
  • Exploring the Multifaceted Landscape of MASLD: A Comprehensive Synthesis of Recent Studies, from Pathophysiology to Organoids and Beyond
    Allison Soto, Colby Spongberg, Alessandro Martinino, Francesco Giovinazzo
    Biomedicines.2024; 12(2): 397.     CrossRef
  • Metabolic dysfunction-associated steatotic liver disease: A silent pandemic
    Arghya Samanta, Moinak Sen Sarma
    World Journal of Hepatology.2024; 16(4): 511.     CrossRef
  • Plasma ALS and Gal-3BP differentiate early from advanced liver fibrosis in MASLD patients
    David Pérez Compte, Lucas Etourneau, Anne-Marie Hesse, Alexandra Kraut, Justine Barthelon, Nathalie Sturm, Hélène Borges, Salomé Biennier, Marie Courçon, Marc de Saint Loup, Victoria Mignot, Charlotte Costentin, Thomas Burger, Yohann Couté, Christophe Bru
    Biomarker Research.2024;[Epub]     CrossRef
  • Cardiac abnormalities pre- and post-liver transplantation for metabolic dysfunction-associated steatohepatitis – Evidence and special considerations
    Steven M. Elzein, Elizabeth W. Brombosz, Sudha Kodali
    Journal of Liver Transplantation.2024; 15: 100228.     CrossRef
  • Serum Creatinine as an Independent Predictor of Moderate to Severe Fibrosis in Chinese American Non-obese Metabolic Dysfunction-Associated Steatotic Liver Disease
    Michael Sun, Vincent J Yao, Aivi A Rahman, Kevin Liu, Saud Rehman, Amber Sun, Alan C Yao
    Cureus.2024;[Epub]     CrossRef
  • Recent trends and new developments in liver transplantation
    Yasuhiko Sugawara, Taizo Hibi
    BioScience Trends.2024; 18(3): 206.     CrossRef
  • Cenicriviroc Suppresses and Reverses Steatohepatitis by Regulating Macrophage Infiltration and M2 Polarization in Mice
    Guanliang Chen, Yanwen Yu, Yuqin Zhu, Mayumi Nagashimada, Yajiao Wang, Naoto Nagata, Liang Xu
    Endocrinology.2024;[Epub]     CrossRef
  • Metabolic bariatric surgery, alcohol misuse and liver cirrhosis: a narrative review
    Matthew L. Basa, Danielle S. Cha, David P. Mitchell, Daniel L. Chan
    Metabolism and Target Organ Damage.2024;[Epub]     CrossRef
  • The interrelation of cardiometabolic risk factors and metabolic dysfunction-associated steatotic liver disease subtypes
    A. Yu. Ishchenko, M. Yu. Galushko, I. G. Bakulin
    Meditsinskiy sovet = Medical Council.2024; (15): 146.     CrossRef
  • Cardio-metabolic disorders in a patient with non-alcoholic fatty liver disease and normal body weight
    Svetlana V. Turkina, Mikhail E. Statsenko, Irina A. Tyshchenko, Marina N. Titarenko, Marina A. Kosivtsova, Elena E. Gorbacheva
    Journal of Volgograd State Medical University.2024; 21(3): 109.     CrossRef
  • Exploring the knowledge and attitudes towards metabolic dysfunction associated fatty liver disease (MAFLD): Validation and correlations of MAFLD-knowledge questionnaire and MAFLD-attitude questionnaire
    Samah Al Tawil, Mohamad Abdelkhalik, Adam El Fouani, Nour Allakiss, Lama Mattar, Wissam H. Faour, Rajaa Chatila
    Heliyon.2024; 10(22): e40217.     CrossRef
  • Weight Loss After Sleeve Gastrectomy According to Metabolic Dysfunction-Associated Steatotic Liver Disease Stage in Patients with Obesity: A Liver Biopsy-Based Prospective Study
    José Ignacio Martínez-Montoro, Isabel Arranz-Salas, Carolina Gutiérrez-Repiso, Ana Sánchez-García, Luis Ocaña-Wilhelmi, José M. Pinazo-Bandera, Diego Fernández-García, Araceli Muñoz-Garach, Dieter Morales-García, Miren García-Cortés, Eduardo García-Fuente
    Nutrients.2024; 16(22): 3857.     CrossRef
  • Liver transplantation for alcohol-related liver disease in Korea: The need for patient management guidelines
    Soon Kyu Lee
    Annals of Liver Transplantation.2024; 4(2): 40.     CrossRef
  • Post-transplant complications in alcohol- and metabolic-associated steatotic liver disease
    Shekhar Singh Jadaun, Sanjiv Saigal
    Metabolism and Target Organ Damage.2024;[Epub]     CrossRef
  • How to optimize the outcome of liver transplantation for non-alcoholic fatty liver disease
    Byeong Geun Song, Dong Hyun Sinn
    Clinical and Molecular Hepatology.2023; 29(2): 411.     CrossRef
  • Liver fibrosis and MAFLD: the exploration of multi-drug combination therapy strategies
    Qingfu Dong, Haolin Bao, Jiangang Wang, Wujiang Shi, Xinlei Zou, Jialin Sheng, Jianjun Gao, Canghai Guan, Haoming Xia, Jinglin Li, Pengcheng Kang, Yi Xu, Yunfu Cui, Xiangyu Zhong
    Frontiers in Medicine.2023;[Epub]     CrossRef
  • Diabetes and Metabolic Disorders: Their Impact on Cardiovascular Events in Liver Transplant Patients
    Simone Di Cola, Giulia Cusi, Lucia Lapenna, Jakub Gazda, Stefano Fonte, Marco Mattana, Gianluca Mennini, Patrizio Pasqualetti, Manuela Merli, Xingshun Qi
    Canadian Journal of Gastroenterology and Hepatology.2023; 2023: 1.     CrossRef
  • Evaluation and Management of Nutritional Consequences of Chronic Liver Diseases
    Silvia Espina, Diego Casas-Deza, Vanesa Bernal-Monterde, María José Domper-Arnal, Sandra García-Mateo, Alberto Lué
    Nutrients.2023; 15(15): 3487.     CrossRef
  • New Developments and Challenges in Liver Transplantation
    Amjad Khalil, Alberto Quaglia, Pierre Gélat, Nader Saffari, Hassan Rashidi, Brian Davidson
    Journal of Clinical Medicine.2023; 12(17): 5586.     CrossRef
  • Outcomes in elderly patients undergoing hepatic resection compared to liver transplant for hepatocellular carcinoma
    Sameer A. Khan, Fasih A. Ahmed, Muhammad S. Hafeez, Lawrence R. Feng, Abhinav Seth, Yong K. Kwon, Hassan Aziz
    Journal of Surgical Oncology.2023; 128(8): 1320.     CrossRef
  • 13,237 View
  • 299 Download
  • 39 Web of Science
  • Crossref

Steatotic liver disease

Causes and risk profiles of mortality among individuals with nonalcoholic fatty liver disease
Peter Konyn, Aijaz Ahmed, Donghee Kim
Clin Mol Hepatol 2023;29(Suppl):S43-S57.
Published online November 22, 2022
DOI: https://doi.org/10.3350/cmh.2022.0351
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States and worldwide. Though nonalcoholic fatty liver per se may not be independently associated with an increased risk for all-cause mortality, it is associated with a number of harmful metabolic risk factors, such as type 2 diabetes mellitus, hyperlipidemia, obesity, a sedentary lifestyle, and an unhealthy diet. The fibrosis stage is a predictor of all-cause mortality in NAFLD. Mortality in individuals with NAFLD has been steadily increasing, and the most common cause-specific mortality for NAFLD is cardiovascular disease, followed by extra-hepatic cancer, liver-related mortality, and diabetes. High-risk profiles for mortality in NAFLD include PNPLA3 I148M polymorphism, low thyroid function and hypothyroidism, and sarcopenia. Achieving weight loss through adherence to a high-quality diet and sufficient physical activity is the most important predictor of improvement in NAFLD severity and the benefit of survival. Given the increasing health burden of NAFLD, future studies with more long-term mortality data may demonstrate an independent association between NAFLD and mortality.

Citations

Citations to this article as recorded by  Crossref logo
  • Dietary vitamin E intake in metabolic dysfunction–associated steatotic liver disease and all-cause/cause-specific mortality
    Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, Aijaz Ahmed
    European Journal of Gastroenterology & Hepatology.2026; 38(1): 63.     CrossRef
  • Unveiling the Burden of Steatotic Liver Disease: Mortality Risks by Subtype and Fibrosis Stage in a Nationwide Cohort
    Qi Feng, Pinelopi Manousou, Chioma N. Izzi‐Engbeaya, Rohit Loomba, Mark Thursz, Mark Woodward
    Liver International.2026;[Epub]     CrossRef
  • Secondary Growth Hormone Deficiency That Developed into Cirrhosis after Several Years of Interrupted Growth Hormone Replacement Therapy
    Ayana Sueki, Daisuke Kaya, Shinsaku Nagamatsu, Chisa Yamamoto, Kohei Ohta, Yuya Matsuo, Yuya Nishio, Yusuke Komeda, Shoma Kikukawa, Kyohei Matsuura, Hideki Matsuo, Masakazu Uejima, Kei Moriya
    Internal Medicine.2025; 64(3): 387.     CrossRef
  • Liver Cancer Risk Across Metabolic Dysfunction-Associated Steatotic Liver Disease and/or Alcohol: A Nationwide Study
    Byungyoon Yun, Heejoo Park, Sang Hoon Ahn, Juyeon Oh, Beom Kyung Kim, Jin-Ha Yoon
    American Journal of Gastroenterology.2025; 120(2): 410.     CrossRef
  • The Fibrosis-4 index predicts all-cause mortality in a cohort of patients at high cardiovascular risk partly through glomerular filtration rate reduction
    Antonio Mirijello, Gabriella Pacilli, Antonio Siena, Antonio Mangiacotti, Maria Maddalena D'Errico, Daria Dilalla, Olga Lamacchia, Andrea Fontana, Massimiliano Copetti, Pamela Piscitelli, Giovanni Targher, Salvatore A. De Cosmo
    Nutrition, Metabolism and Cardiovascular Diseases.2025; 35(1): 103768.     CrossRef
  • Secondhand Smoke Exposure and Metabolic Dysfunction-associated Steatotic Liver Disease in US Adolescents
    Donghee Kim, Brandon J. Perumpail, Pojsakorn Danpanichkul, Karn Wijarnpreecha, Aijaz Ahmed
    Clinical Gastroenterology and Hepatology.2025; 23(4): 665.     CrossRef
  • Letter: Towards Better Intervention Strategies for MASLD and MetALD—What Are We Missing? Authors' Reply
    Yewan Park, Jooyi Jung, Gi‐Ae Kim
    Alimentary Pharmacology & Therapeutics.2025; 61(2): 400.     CrossRef
  • Red cell distribution width/platelet ratio predicts decompensation of metabolic dysfunction-associated steatotic liver disease-related compensated advanced chronic liver disease
    Ming-Hua Zheng, Amedeo Lonardo
    World Journal of Gastroenterology.2025;[Epub]     CrossRef
  • PNPLA3 is one of the bridges between TM6SF2 E167K variant and MASLD: Correspondence to editorial on “TM6SF2 E167K variant decreases PNPLA3-mediated PUFA transfer to promote hepatic steatosis and injury in MASLD”
    Baokai Sun, Likun Zhuang
    Clinical and Molecular Hepatology.2025; 31(1): e67.     CrossRef
  • Role of noninvasive tests on the prediction of hepatocellular carcinoma in nonalcoholic fatty liver disease patients without cirrhosis: a systematic review and meta-analysis of aggregate and individual patient data
    Nanicha Siriwong, Supachaya Sriphoosanaphan, Pakanat Decharatanachart, Tanat Yongpisarn, Stephen J. Kerr, Sombat Treeprasertsuk, Thodsawit Tiyarattanachai, Terapap Apiparakoon, Hannes Hagström, Camilla Akbari, Mattias Ekstedt, Terry Cheuk-Fung Yip, Grace
    European Journal of Gastroenterology & Hepatology.2025; 37(3): 358.     CrossRef
  • Unmet needs of metabolic dysfunction – Associated “fatty or steatotic” liver disease
    Yu-Ming Cheng, Shao-Wen Wang, Ching Wang, Chia-Chi Wang
    Tzu Chi Medical Journal.2025; 37(2): 152.     CrossRef
  • Association Between Handgrip Strength and Cardiovascular Disease Risk in MASLD: A Prospective Study From UK Biobank
    Tae Seop Lim, Sujin Kwon, Sung A. Bae, Hye Yeon Chon, Seol A. Jang, Ja Kyung Kim, Chul Sik Kim, Seok Won Park, Kyoung Min Kim
    Journal of Cachexia, Sarcopenia and Muscle.2025;[Epub]     CrossRef
  • Metabolic dysfunction-associated steatotic liver disease (MASLD): a systemic disease with a variable natural history and challenging management
    Luigi Elio Adinolfi, Aldo Marrone, Luca Rinaldi, Riccardo Nevola, Antonio Izzi, Ferdinando Carlo Sasso
    Exploration of Medicine.2025;[Epub]     CrossRef
  • The relationship between serum uric acid level and non-alcoholic fatty liver disease in northern China: a retrospective cohort study
    Qian He, Xinyue Liu, Guoyong Ding, Yiying Wang, Xiaoting Luo, Wenyuan Cao, Weijia Xing
    BMC Public Health.2025;[Epub]     CrossRef
  • Novel pyranopyridine derivatives and their radiolabeled nanoconjugates: An augmented approach for targeted cancer theranostics
    Hesham A. Shamsel-Din, Mohamed M. Swidan, Ahmed B. Ibrahim, Mohamed A. Motaleb, Tamer M. Sakr
    Journal of Drug Delivery Science and Technology.2025; 107: 106802.     CrossRef
  • Metabolic dysfunction-associated steatotic liver disease in adults
    Daniel Q. Huang, Vincent W. S. Wong, Mary E. Rinella, Jerome Boursier, Jeffrey V. Lazarus, Hannele Yki-Järvinen, Rohit Loomba
    Nature Reviews Disease Primers.2025;[Epub]     CrossRef
  • Elevated red blood cell folate levels are associated with metabolic dysfunction-associated steatotic liver disease: results from NHANES 2017–2020
    Xin Liao, Song Yu, Lin Wang, Ruyue Zhang, Ke Yu
    Frontiers in Physiology.2025;[Epub]     CrossRef
  • Association of High‐Sensitivity Troponins in Metabolic Dysfunction‐Associated Steatotic Liver Disease With All‐Cause and Cause‐Specific Mortality
    Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, George Cholankeril, Aijaz Ahmed
    Alimentary Pharmacology & Therapeutics.2025; 61(11): 1785.     CrossRef
  • Addressing the burden of steatotic liver disease: The role of transient elastography: Correspondence to editorial on “Current burden of steatotic liver disease and fibrosis among adults in the United States, 2017-2023”
    Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, George Cholankeril, Rohit Loomba, Aijaz Ahmed
    Clinical and Molecular Hepatology.2025; 31(2): e180.     CrossRef
  • The burden of steatotic liver disease before and during the COVID-19 pandemic: Correspondence to editorial on “Current burden of steatotic liver disease and fibrosis among adults in the United States, 2017-2023”
    Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, George Cholankeril, Rohit Loomba, Aijaz Ahmed
    Clinical and Molecular Hepatology.2025; 31(2): e183.     CrossRef
  • Current burden of steatotic liver disease and fibrosis among adults in the United States, 2017–2023
    Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, George Cholankeril, Rohit Loomba, Aijaz Ahmed
    Clinical and Molecular Hepatology.2025; 31(2): 382.     CrossRef
  • Associations between non-insulin-based insulin resistance surrogate markers and liver-related outcomes in metabolic dysfunction-associated steatotic liver disease: a nationwide cohort study in South Korea
    Sang Yi Moon, Minkook Son, Yeo Wool Kang, Myeongseok Koh, Jong Yoon Lee, Yang Hyun Baek
    BMC Gastroenterology.2025;[Epub]     CrossRef
  • Response to the Letter to the Editor: What Is the Optimal Anti‐Diabetic Regimen Among CHB and T2DM Patients?
    Beom Kyung Kim
    Liver International.2025;[Epub]     CrossRef
  • The new definition of metabolic dysfunction-associated steatotic liver disease: the role of ultrasound and elastography
    Xinrui Jin, Terry Cheuk-Fung Yip, Grace Lai-Hung Wong, Vincent Wai-Sun Wong, Jimmy Che-To Lai
    Ultrasonography.2025; 44(3): 189.     CrossRef
  • Association between dietary amino acid intake and the risk of metabolic dysfunction-associated steatotic liver disease
    Ruoqi Zhou, Xinrong Zhang, Xinxin Liu, Rui Huang, Yuwei Wang, Dajing Xia, Xue Li, Yihua Wu, Yu Shi
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Special topic: Alcoholic liver diseases
The 14th International Symposium on Alcoholic Liver and Pancreatic Diseases and Cirrhosis (ISALPDC)

Alcohol-related liver disease

Obesity and binge alcohol intake are deadly combination to induce steatohepatitis: A model of high-fat diet and binge ethanol intake
Seonghwan Hwang, Tianyi Ren, Bin Gao
Clin Mol Hepatol 2020;26(4):586-594.
Published online September 17, 2020
DOI: https://doi.org/10.3350/cmh.2020.0100
Obesity and binge drinking often coexist and work synergistically to promote steatohepatitis; however, the underlying mechanisms remain obscure. In this mini-review, we briefly summarize clinical evidence of the synergistical effect of obesity and heavy drinking on steatohepatitis and discuss the underlying mechanisms obtained from the study of several mouse models. High-fat diet (HFD) feeding and binge ethanol synergistically induced steatohepatitis and fibrosis in mice with significant intrahepatic neutrophil infiltration; such HFD-plus-ethanol treatment markedly up-regulated the hepatic expression of many chemokines with the highest fold (approximately 30-fold) induction of chemokine (C-X-C motif) ligand 1 (Cxcl1), which contributes to hepatic neutrophil infiltration and liver injury. Furthermore, HFD feeding activated peroxisome proliferator-activated receptor gamma that subsequently inhibited CXCL1 upregulation in hepatocytes, thereby forming a negative feedback loop to prevent neutrophil overaction; whereas binge ethanol blocked this loop and then exacerbated CXCL1 elevation, neutrophil infiltration, and liver injury. Interestingly, inflamed mouse hepatocytes attracted neutrophils less effectively than inflamed human hepatocytes due to the lower induction of CXCL1 and the lack of the interleukin (IL)-8 gene in the mouse genome, which may be one of the reasons for difficulty in development of mouse models of alcoholic steatohepatitis and nonalcoholic steatohepatitis (NASH). Hepatic overexpression of Cxcl1 and/or IL-8 promoted steatosis-to-NASH progression in HFD-fed mice by inducing neutrophil infiltration, oxidative stress, hepatocyte death, fibrosis, and p38 mitogen-activated protein kinase activation. Collectively, obesity and binge drinking synergistically promote steatohepatitis via the induction of CXCL1 and subsequent hepatic neutrophil infiltration.

Citations

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Reviews

Steatotic liver disease

NASH Therapy: omega 3 supplementation, vitamin E, insulin sensitizers and statin drugs
Stephen Caldwell
Clin Mol Hepatol 2017;23(2):103-108.
Published online May 10, 2017
DOI: https://doi.org/10.3350/cmh.2017.0103
Non-alcoholic steatohepatitis (NASH) is the more aggressive form of non-alcoholic fatty liver disease (NAFLD). NASH can progress to hepatic fibrosis, cirrhosis, portal hypertension and primary liver cancer. Therapy is evolving with a substantial number of trials of promising new agents now in progress. In this article however, we will examine data for several older forms of therapy which have been fairly extensively studied over the years: Polyunsaturated Fatty Acid (PUFA) supplements, vitamin E, insulin sensitizing agents with a focus on pioglitazone and statin agents. Early interest in PUFA derived from their potential benefit in cardio-metabolic disease and the close association of NAFLD/NASH with Metabolic Syndrome. Results have been variable although most studies show reduction of liver fat without other major effects and their effects are influenced by concomitant weight loss and underlying genetic factors. Vitamin E has had some efficacy in pediatric NASH but questionable efficacy in even mild NASH among adults. Pioglitazone has shown significant histological benefit in a number of trials but concern over side-effects (especially weight gain) have dampened enthusiasm. A newer insulin sensitizer, liraglutide, has also shown promise in a small randomized, controlled trial. Very limited data exists regarding the histological effects of the statins in NASH and these agents appear to be fairly neutral with neither clear cut benefit nor detriment. Their use is best guided by cardiovascular risks rather than liver histology.

Citations

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Steatotic liver disease

Genetic predisposition in nonalcoholic fatty liver disease
Silvia Sookoian, Carlos J. Pirola
Clin Mol Hepatol 2017;23(1):1-12.
Published online March 9, 2017
DOI: https://doi.org/10.3350/cmh.2016.0109
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease whose prevalence has reached global epidemic proportions. Although the disease is relatively benign in the early stages, when severe clinical forms, including nonalcoholic steatohepatitis (NASH), cirrhosis and even hepatocellular carcinoma, occur, they result in worsening the long-term prognosis. A growing body of evidence indicates that NAFLD develops from a complex process in which many factors, including genetic susceptibility and environmental insults, are involved. In this review, we focused on the genetic component of NAFLD, with special emphasis on the role of genetics in the disease pathogenesis and natural history. Insights into the topic of the genetic susceptibility in lean individuals with NAFLD and the potential use of genetic tests in identifying individuals at risk are also discussed.

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Original Article

Steatotic liver disease

Enhanced A-FABP expression in visceral fat: potential contributor to the progression of NASH
Min Yong Yoon, Jun Mo Sung, Chang Seok Song, Won Young Lee, Eun Jung Rhee, Jun Ho Shin, Chang Hak Yoo, Seoung Wan Chae, Ja Yeon Kim, Wook Jin, Yong Kyun Cho
Korean J Hepatol 2012;18(3):279-286.
Published online September 25, 2012
DOI: https://doi.org/10.3350/cmh.2012.18.3.279
Background/Aims

Adipose tissue is an active endocrine organ that secretes various metabolically important substances including adipokines, which represent a link between insulin resistance and nonalcoholic steatohepatitis (NASH). The factors responsible for the progression from simple steatosis to steatohepatitis remain elusive, but adipokine imbalance may play a pivotal role. We evaluated the expressions of adipokines such as visfatin, adipocyte-fatty-acid-binding protein (A-FABP), and retinol-binding protein-4 (RBP-4) in serum and tissue. The aim was to discover whether these adipokines are potential predictors of NASH.

Methods

Polymerase chain reaction, quantification of mRNA, and Western blots encoding A-FABP, RBP-4, and visfatin were used to study tissue samples from the liver, and visceral and subcutaneous adipose tissue. The tissue samples were from biopsy specimens obtained from patients with proven NASH who were undergoing laparoscopic cholecystectomy due to gallbladder polyps.

Results

Patients were classified into two groups: NASH, n=10 and non-NASH, n=20 according to their nonalcoholic fatty liver disease Activity Score. Although serum A-FABP levels did not differ between the two groups, the expressions of A-FABP mRNA and protein in the visceral adipose tissue were significantly higher in NASH group than in non-NASH group (104.34 vs. 97.05, P<0.05, and 190.01 vs. 95.15, P<0.01, respectively). Furthermore, the A-FABP protein expression ratio between visceral adipose tissue and liver was higher in NASH group than in non-NASH group (4.38 vs. 1.64, P<0.05).

Conclusions

NASH patients had higher levels of A-FABP expression in their visceral fat compared to non-NASH patients. This differential A-FABP expression may predispose patients to the progressive form of NASH.

Citations

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Review

Nonalcoholic steatohepatitis: Pathogenesis and treatment
Sang Hoon Park
Korean J Hepatol 2008;14(1):12-27.
Published online March 20, 2008
DOI: https://doi.org/10.3350/kjhep.2008.14.1.12
Nonalcoholic fatty liver disease (NAFLD) is characterized by a wide spectrum of liver damage spanning steatosis, nonalcoholic steatohepatitis (NASH), cryptogenic liver cirrhosis, and even to hepatocellular carcinoma. Investigations in the last few years have focused on NASH, a relatively aggressive form of liver disease, due largely to the explosion of information provided by clinical and basic science studies related to the widespread presence of risk factors, such as obesity, type II diabetes mellitus, and dyslipidemia. This is especially important given that obesity and type II diabetes mellitus have recently reached epidemic proportions in Korea. The pathogenesis of NASH is multifactorial, with insulin resistance and increased fatty acid possibly being important factors in the accumulation of hepatocellular fat, and oxidant stress, lipid peroxidation, mitochondrial dysfunction, and dysregulation of variable cytokines possibly being important causes of hepatocellular injury in steatotic liver. Because not all steatotic livers progress to NASH, some other environmental factors or a combination of genetic factors are thought to be required for progression to NASH and fibrosis. Lifestyle modifications continue to be the cornerstone therapy in NAFLD, but some insulin-sensitizing drugs might be more effective in treating NASH. Many pilot trials for antioxidants and lipid-lowering and hepatic protective agents have yielded promising initial results in improving liver enzymes or features of liver histology. However, the efficacy of these agents remains questionable. Despite recent gains in understanding NASH, several issues related to its natural history, pathogenesis, and treatment remain unresolved. (Korean J Hepatol 2008;14:12- 27)

Citations

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  • Elevated red cell distribution width is associated with advanced fibrosis in NAFLD
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  • Ko NOMURA
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Original Article

The Prevalence of Metabolic Syndrome in Patients with Nonalcoholic Fatty Liver Disease
Ki Won Moon, M.D., Joung Muk Leem, M.D., Sang Seok Bae, M.D., Ki Man Lee, M.D., Seok Hyung Kim, M.D.*, Hee Bok Chae, M.D., Seon Mee Park, M.D. and Sei Jin Youn, M.D.
Korean J Hepatol 2004;10(3):197-206.
Background/Aims
Nonalcoholic fatty liver disease (NAFLD) is associated with dyslipidemia, obesity, and insulin resistance, which are the main features of metabolic syndrome. First, we examined the prevalence of metabolic syndrome among patients with NAFLD . We then compared the prevalence of metabolic syndrome in simple steatosis with that in nonalcoholic steatohepatitis (NASH). Finally, we sought to identify clinical factors associated with the stage of liver fibrosis. Methods: From November 2002 to March 2004, we enrolled consecutive 25 patients with NAFLD from patients visiting outpatient clinic. The 17 controls were healthy persons w ho visited our health promotion center. We compared the clinical and biochemical data of the NAFLD group with those of the control group. Using histologic findings, we divided NAFLD into simple steatosis and NASH. We then compared the clinical and biochemical data of the simple steatosis group with those of the NASH group. Results: Fourteen patients (14/25, 56%) had metabolic syndrome in the NAFLD group. There was no difference in the prevalence of metabolic syndrome between the simple steatosis (5/10, 50%) and the NASH group (9/15, 60%). We found significant differences in cardiovascular risk factors between the two groups, but homeostasis model assessment insulin resistance w as the only significantly different factor between the simple steatosis group and the NASH group. In addition, no difference in histological features was found between NASH with metabolic syndrome and without metabolic syndrome. Conclusions: A considerable number of patients with NAFLD had metabolic syndrome. There was a close correlation between NAFLD and metabolic syndrome. We could not find any cardiovascular risk factors that could predict a severe fibrosis. (Korean J Hepatol 2004;10:197-206)
  • 3,972 View
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Liver Pathology
Nonalcoholic Steatohepatitis
So-Young Jin
Korean J Hepatol 2006;12(3):455-459.
  • 3,444 View
  • 21 Download