The metabolic dysfunction that characterizes obesity and type 2 diabetes mellitus affects not only the heart and kidneys, but also the liver. Although lifestyle modification remains the cornerstone in the management of metabolic liver diseases, the field has progressed this year, with a new definition, validation of non-invasive biomarkers and numerous clinical trials.
Key advances
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Panels of non-invasive biomarkers have the potential to diagnose patients with NASH and those with NASH and fibrosis4.
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Panels of non-invasive biomarkers have predictive value for outcomes, especially those capturing the degree of fibrosis6.
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Drugs targeting new targets, such as thyroid hormone receptor-β and fibroblast growth factor 21, showed positive results in clinical trials8,9.
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There is a high degree of variability in the responses of the placebo groups in these trials8,9.
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References
Dufour, J. F. Time to abandon NASH? Hepatology 63, 9–10 (2016).
Rinella, M. E. et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology 78, 1966–1986 (2023).
Angulo, P. et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology 149, 389–97.e10 (2015).
Sanyal, A. J. et al. Diagnostic performance of circulating biomarkers for non-alcoholic steatohepatitis. Nat. Med. 29, 2656–2664 (2023).
Ravaioli, F. et al. Diagnostic accuracy of FibroScan-AST (FAST) score for the non-invasive identification of patients with fibrotic non-alcoholic steatohepatitis: a systematic review and meta-analysis. Gut 72, 1399–1409 (2023).
Mózes, F. E. et al. Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis. Lancet Gastroenterol. Hepatol. 8, 704–713 (2023).
Harrison, S. A. et al. Resmetirom for nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled phase 3 trial. Nat. Med. 29, 2919–2928 (2023).
Loomba, R. et al. Randomized, controlled trial of the FGF21 analogue pegozafermin in NASH. N. Engl. J. Med. 389, 998–1008 (2023).
Harrison, S. A. et al. Safety and efficacy of once-weekly efruxifermin versus placebo in non-alcoholic steatohepatitis (HARMONY): a multicentre, randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Gastroenterol. Hepatol. 8, 1080–1093 (2023).
Dufour, J. F., Caussy, C. & Loomba, R. Combination therapy for non-alcoholic steatohepatitis: rationale, opportunities and challenges. Gut 69, 1877–1884 (2020).
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J.-F.D. declares the following competing interests: participation on advisory committees for Alentis, Astra-Zeneca, Bayer, Bristol-Myers Squibb, Enyo, Esai, Genfit, Intercept, Inventiva, Ipsen, Lilly, Madrigal, Merck, Novartis, Novo-Nordisk and Roche. Speaking and teaching engagements for Astra-Zeneca, Bristol-Myers Squibb, Intercept, Ipsen and Roche.
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Dufour, JF. A pivotal year for NAFLD and NASH therapeutics. Nat Rev Endocrinol 20, 75–76 (2024). https://doi.org/10.1038/s41574-023-00939-9
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DOI: https://doi.org/10.1038/s41574-023-00939-9
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