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Recompensation in cirrhosis: unravelling the evolving natural history of nonalcoholic fatty liver disease

Nature Reviews Gastroenterology & Hepatology volume 21, pages 46–56 (2024)Cite this article

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Abstract

Recompensation has gained increasing attention in the field of cirrhosis, particularly in chronic liver disease with a definite aetiology. The current global prevalence of obesity and nonalcoholic fatty liver disease (NAFLD) is increasing, but there is currently a lack of a clear definition for recompensation in NAFLD-related cirrhosis. Here, we provide an up-to-date perspective on the natural history of NAFLD, emphasizing the reversible nature of the disease, summarizing possible mechanisms underlying recompensation in NAFLD, discussing challenges that need to be addressed and outlining future research directions in the field. Recompensation is a promising goal in patients with NAFLD-related cirrhosis, and further studies are needed to explore its underlying mechanisms and uncover its clinical features.

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Fig. 1: The up-to-date natural history of NAFLD.
Fig. 2: Possible main mechanisms of recompensation in nonalcoholic fatty liver disease-related cirrhosis.

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Acknowledgements

The authors thank the members of the CHESS-MAFLD consortium for their coordination.

Author information

Authors and Affiliations

  1. Xi’an Medical University, Xi’an, China

    Gong Feng

  2. The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

    Gong Feng

  3. Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy

    Luca Valenti

  4. Precision Medicine, Biological Resource Center and Department of Transfusion Medicine, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Luca Valenti

  5. Medical Data Analytics Center, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China

    Vincent Wai-Sun Wong

  6. State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China

    Vincent Wai-Sun Wong

  7. Department of Endemic Medicine and Gastroenterology, Faculty of Medicine, Minia University, Minia, Egypt

    Yasser Mahrous Fouad

  8. Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey

    Yusuf Yilmaz

  9. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

    Won Kim

  10. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Korea

    Won Kim

  11. Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada

    Giada Sebastiani

  12. Inova Medicine Services, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, VA, USA

    Zobair M. Younossi

  13. Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic Barcelona,-IDIBAPS, University of Barcelona, Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Spain

    Virginia Hernandez-Gea

  14. MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

    Ming-Hua Zheng

  15. Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China

    Ming-Hua Zheng

Authors
  1. Gong Feng
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  2. Luca Valenti
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  3. Vincent Wai-Sun Wong
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  4. Yasser Mahrous Fouad
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  5. Yusuf Yilmaz
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  6. Won Kim
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  7. Giada Sebastiani
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  8. Zobair M. Younossi
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  9. Virginia Hernandez-Gea
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  10. Ming-Hua Zheng
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Contributions

G.F. researched data for the article. All authors contributed substantially to discussion of the content. M.-H.Z. and G.F. wrote the article. All authors reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Ming-Hua Zheng.

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Competing interests

L.V. reports consulting fees from Gilead Sciences, Pfizer, AstraZeneca, Novo Nordisk, Intercept pharmaceuticals, Diatech Pharmacogenetics, IONIS and Viatris; honoraria from MSD, Gilead Sciences, AlfaSigma, AbbVie and Resalis; and grants from Gilead Sciences. V.W.-S.W. reports grants from Gilead Sciences; consulting fees from AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Intercept, Inventiva, Novo Nordisk, Pfizer and TARGET PharmaSolutions; and honoraria for lectures from Abbott, AbbVie, Gilead Sciences and Novo Nordisk; and is Chairman of Subspecialty Board of Gastroenterology and Hepatology, Hong Kong College of Physicians, and Co-founder of Illuminatio Medical Technology. Y.Y. is a consultant to Zydus, Cymabay and Novo Nordisk. W.K. reports grants from GSK, Gilead Sciences, Novartis, Pfizer, Roche, Springbank, Ildong, Galmed, Dicerna, Enyo, Hanmi, Novo Nordisk and KOBIOLABS; reports consulting fees from Boehringer Ingelheim, Novo Nordisk, Standigm, Daewoong, TSD Life Sciences, Ildong, Olix Pharma, HK Inoen and KOBIOLABS; honoraria for lectures from Ildong, Samil and Novo Nordisk; owns stocks in KOBIOLABS and Lepidyne; and is the founder of Remedygen. G.S. reports honoraria from Merck, Gilead Sciences, Abbvie, Intercept, Novo Nordisk and Pfizer; and unrestricted research funding from Theratechnologies. Z.M.Y. is a consultant to BMS, Gilead Sciences, AbbVie, Intercept and GSK. V.H.-G. reports honoraria for lectures from GORE and Cook Medical. M.-H.Z. and Y.M.F. declare no competing interests.

Peer review

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Nature Reviews Gastroenterology & Hepatology thanks Takumi Kawaguchi, and the other, anonymous, reviewer for their contribution to the peer review of this work.

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Feng, G., Valenti, L., Wong, V.WS. et al. Recompensation in cirrhosis: unravelling the evolving natural history of nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol 21, 46–56 (2024). https://doi.org/10.1038/s41575-023-00846-4

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