{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T00:02:16Z","timestamp":1794009736002,"version":"4.8.0"},"reference-count":158,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Rev Gastroenterol Hepatol"],"published-print":{"date-parts":[[2026,6]]},"DOI":"10.1038\/s41575-026-01187-8","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T17:01:33Z","timestamp":1773853293000},"page":"460-474","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Therapeutic targets for metabolic dysfunction-associated steatohepatitis: a personalized approach to disease management"],"prefix":"10.1038","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0620-9705","authenticated-orcid":false,"given":"Mary E.","family":"Rinella","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5929-5470","authenticated-orcid":false,"given":"Silvia","family":"Sookoian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"1187_CR1","doi-asserted-by":"publisher","first-page":"1966","DOI":"10.1097\/HEP.0000000000000520","volume":"78","author":"ME Rinella","year":"2023","unstructured":"Rinella, M. E. et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology 78, 1966\u20131986 (2023).","journal-title":"Hepatology"},{"key":"1187_CR2","doi-asserted-by":"publisher","first-page":"S32","DOI":"10.3350\/cmh.2024.0431","volume":"31","author":"ZM Younossi","year":"2025","unstructured":"Younossi, Z. M., Kalligeros, M. & Henry, L. Epidemiology of metabolic dysfunction-associated steatotic liver disease. Clin. Mol. Hepatol. 31, S32\u2013S50 (2025).","journal-title":"Clin. Mol. Hepatol."},{"key":"1187_CR3","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1016\/S2468-1253(21)00308-3","volume":"6","author":"A Mantovani","year":"2021","unstructured":"Mantovani, A. et al. Non-alcoholic fatty liver disease and risk of fatal and non-fatal cardiovascular events: an updated systematic review and meta-analysis. Lancet Gastroenterol. Hepatol. 6, 903\u2013913 (2021).","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"1187_CR4","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1136\/gutjnl-2020-323082","volume":"71","author":"A Mantovani","year":"2022","unstructured":"Mantovani, A. et al. Non-alcoholic fatty liver disease and risk of incident chronic kidney disease: an updated meta-analysis. Gut 71, 156\u2013162 (2022).","journal-title":"Gut"},{"key":"1187_CR5","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1136\/gutjnl-2021-324191","volume":"71","author":"A Mantovani","year":"2022","unstructured":"Mantovani, A. et al. Non-alcoholic fatty liver disease and increased risk of incident extrahepatic cancers: a meta-analysis of observational cohort studies. Gut 71, 778\u2013788 (2022).","journal-title":"Gut"},{"key":"1187_CR6","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1016\/j.cgh.2023.09.018","volume":"22","author":"KE Chan","year":"2024","unstructured":"Chan, K. E. et al. Longitudinal outcomes associated with metabolic dysfunction-associated steatotic liver disease: a meta-analysis of 129 studies. Clin. Gastroenterol. Hepatol. 22, 488\u2013498.e14 (2024).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"1187_CR7","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1038\/s41575-025-01120-5","volume":"22","author":"LA Diaz","year":"2025","unstructured":"Diaz, L. A. et al. Clinical trial design, biomarkers and end points in metabolic and alcohol-related liver disease. Nat. Rev. Gastroenterol. Hepatol. 22, 866\u2013884 (2025).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"1187_CR8","unstructured":"European Medicines Agency. First treatment against liver scarring caused by a type of \u2018fatty liver disease\u2019. EMA https:\/\/www.ema.europa.eu\/en\/news\/first-treatment-against-liver-scarring-caused-type-fatty-liver-disease (2025)."},{"key":"1187_CR9","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1056\/NEJMoa2309000","volume":"390","author":"SA Harrison","year":"2024","unstructured":"Harrison, S. A. et al. A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis. N. Engl. J. Med. 390, 497\u2013509 (2024).","journal-title":"N. Engl. J. Med."},{"key":"1187_CR10","unstructured":"US Food and Drug Administration. FDA approves first treatment for patients with liver scarring due to fatty liver disease. FDA https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-approves-first-treatment-patients-liver-scarring-due-fatty-liver-disease (2024)."},{"key":"1187_CR11","doi-asserted-by":"publisher","first-page":"2089","DOI":"10.1056\/NEJMoa2413258","volume":"392","author":"AJ Sanyal","year":"2025","unstructured":"Sanyal, A. J. et al. Phase 3 trial of semaglutide in metabolic dysfunction-associated steatohepatitis. N. Engl. J. Med. 392, 2089\u20132099 (2025).","journal-title":"N. Engl. J. Med."},{"key":"1187_CR12","unstructured":"US Food and Drug Administration. FDA approves treatment for serious liver disease known as \u2018MASH\u2019. FDA https:\/\/www.fda.gov\/drugs\/news-events-human-drugs\/fda-approves-treatment-serious-liver-disease-known-mash (2025)."},{"key":"1187_CR13","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1056\/NEJMoa2401755","volume":"391","author":"AJ Sanyal","year":"2024","unstructured":"Sanyal, A. J. et al. A phase 2 randomized trial of survodutide in MASH and fibrosis. N. Engl. J. Med. 391, 311\u2013319 (2024).","journal-title":"N. Engl. J. Med."},{"key":"1187_CR14","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1056\/NEJMoa2401943","volume":"391","author":"R Loomba","year":"2024","unstructured":"Loomba, R. et al. Tirzepatide for metabolic dysfunction-associated steatohepatitis with liver fibrosis. N. Engl. J. Med. 391, 299\u2013310 (2024).","journal-title":"N. Engl. J. Med."},{"key":"1187_CR15","doi-asserted-by":"publisher","first-page":"2037","DOI":"10.1038\/s41591-024-03018-2","volume":"30","author":"AJ Sanyal","year":"2024","unstructured":"Sanyal, A. J. et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nat. Med. 30, 2037\u20132048 (2024).","journal-title":"Nat. Med."},{"key":"1187_CR16","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.jhep.2020.02.027","volume":"73","author":"SA Harrison","year":"2020","unstructured":"Harrison, S. A. et al. Selonsertib for patients with bridging fibrosis or compensated cirrhosis due to NASH: results from randomized phase III STELLAR trials. J. Hepatol. 73, 26\u201339 (2020).","journal-title":"J. Hepatol."},{"key":"1187_CR17","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.1053\/j.gastro.2018.07.006","volume":"155","author":"SA Harrison","year":"2018","unstructured":"Harrison, S. A. et al. Simtuzumab is ineffective for patients with bridging fibrosis or compensated cirrhosis caused by nonalcoholic steatohepatitis. Gastroenterology 155, 1140\u20131153 (2018).","journal-title":"Gastroenterology"},{"key":"1187_CR18","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1038\/s41591-018-0104-9","volume":"24","author":"SL Friedman","year":"2018","unstructured":"Friedman, S. L., Neuschwander-Tetri, B. A., Rinella, M. & Sanyal, A. J. Mechanisms of NAFLD development and therapeutic strategies. Nat. Med. 24, 908\u2013922 (2018).","journal-title":"Nat. Med."},{"key":"1187_CR19","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1053\/j.gastro.2015.04.005","volume":"149","author":"E Vilar-Gomez","year":"2015","unstructured":"Vilar-Gomez, E. et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology 149, 367\u2013378.e5 (2015).","journal-title":"Gastroenterology"},{"key":"1187_CR20","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1016\/j.jhep.2020.01.025","volume":"72","author":"P Lampertico","year":"2020","unstructured":"Lampertico, P. et al. Real-world effectiveness and safety of glecaprevir\/pibrentasvir for the treatment of patients with chronic HCV infection: a meta-analysis. J. Hepatol. 72, 1112\u20131121 (2020).","journal-title":"J. Hepatol."},{"key":"1187_CR21","unstructured":"US Food and Drug Administration. Noncirrhotic Nonalcoholic Steatohepatitis with Liver Fibrosis: Developing Drugs for Treatment \u2014 Guidance for Industry (FDA, 2018)."},{"key":"1187_CR22","unstructured":"European Medicines Agency. Reflection Paper on Regulatory Requirements for the Development of Medicinal Products for Nonalcoholic Steatohepatitis (NASH) (EMA, 2023)."},{"key":"1187_CR23","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1053\/j.gastro.2021.10.051","volume":"162","author":"R Loomba","year":"2022","unstructured":"Loomba, R., Ratziu, V. & Harrison, S. A. Expert panel review to compare FDA and EMA guidance on drug development and endpoints in nonalcoholic steatohepatitis. Gastroenterology 162, 680\u2013688 (2022).","journal-title":"Gastroenterology"},{"key":"1187_CR24","unstructured":"US Food and Drug Administration. Nonalcoholic Steatohepatitis with Compensated Cirrhosis: Developing Drugs for Treatment \u2014 Guidance for Industry (FDA, 2019)."},{"key":"1187_CR25","doi-asserted-by":"publisher","first-page":"1557","DOI":"10.1002\/hep.29085","volume":"65","author":"PS Dulai","year":"2017","unstructured":"Dulai, P. S. et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: systematic review and meta-analysis. Hepatology 65, 1557\u20131565 (2017).","journal-title":"Hepatology"},{"key":"1187_CR26","doi-asserted-by":"publisher","first-page":"1898","DOI":"10.1053\/j.gastro.2005.03.084","volume":"128","author":"V Ratziu","year":"2005","unstructured":"Ratziu, V. et al. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology 128, 1898\u20131906 (2005).","journal-title":"Gastroenterology"},{"key":"1187_CR27","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1016\/j.jhep.2024.06.008","volume":"81","author":"SA Harrison","year":"2024","unstructured":"Harrison, S. A. & Dubourg, J. Liver biopsy evaluation in MASH drug development: think thrice, act wise. J. Hepatol. 81, 886\u2013894 (2024).","journal-title":"J. Hepatol."},{"key":"1187_CR28","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1038\/s41591-023-02242-6","volume":"29","author":"SA Harrison","year":"2023","unstructured":"Harrison, S. A., Allen, A. M., Dubourg, J., Noureddin, M. & Alkhouri, N. Challenges and opportunities in NASH drug development. Nat. Med. 29, 562\u2013573 (2023).","journal-title":"Nat. Med."},{"key":"1187_CR29","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1002\/hep.25606","volume":"56","author":"R D\u2019Ambrosio","year":"2012","unstructured":"D\u2019Ambrosio, R. et al. A morphometric and immunohistochemical study to assess the benefit of a sustained virological response in hepatitis C virus patients with cirrhosis. Hepatology 56, 532\u2013543 (2012).","journal-title":"Hepatology"},{"key":"1187_CR30","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1001\/jama.2024.1447","volume":"331","author":"H Lin","year":"2024","unstructured":"Lin, H. et al. Vibration-controlled transient elastography scores to predict liver-related events in steatotic liver disease. JAMA 331, 1287\u20131297 (2024).","journal-title":"JAMA"},{"key":"1187_CR31","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1016\/j.cgh.2020.06.070","volume":"19","author":"VS Are","year":"2021","unstructured":"Are, V. S., Vuppalanchi, R., Vilar-Gomez, E. & Chalasani, N. Enhanced liver fibrosis score can be used to predict liver-related events in patients with nonalcoholic steatohepatitis and compensated cirrhosis. Clin. Gastroenterol. Hepatol. 19, 1292\u20131293.e3 (2021).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"1187_CR32","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000001509","author":"FA Anania","year":"2025","unstructured":"Anania, F. A. et al. Non-invasive tests: establishing efficacy for metabolic dysfunction-associated steatohepatitis beyond the biopsy \u2014 current perspectives from the Division of Hepatology and Nutrition, US Food and Drug Administration. Hepatology https:\/\/doi.org\/10.1097\/HEP.0000000000001509 (2025).","journal-title":"Hepatology"},{"key":"1187_CR33","unstructured":"US Food and Drug Administration. FDA accepts proposal for reasonably likely surrogate endpoint for \u2018MASH\u2019 all-cause mortality or liver-related events. FDA https:\/\/www.fda.gov\/drugs\/drug-safety-and-availability\/fda-accepts-proposal-reasonably-likely-surrogate-endpoint-mash-all-cause-mortality-or-liver-related (2025)."},{"key":"1187_CR34","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.cgh.2023.04.003","volume":"22","author":"QM Anstee","year":"2024","unstructured":"Anstee, Q. M. et al. Cenicriviroc lacked efficacy to treat liver fibrosis in nonalcoholic steatohepatitis: AURORA phase III randomized study. Clin. Gastroenterol. Hepatol. 22, 124\u2013134.e1 (2024).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"1187_CR35","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.3945\/ajcn.110.007674","volume":"93","author":"JD Browning","year":"2011","unstructured":"Browning, J. D. et al. Short-term weight loss and hepatic triglyceride reduction: evidence of a metabolic advantage with dietary carbohydrate restriction. Am. J. Clin. Nutr. 93, 1048\u20131052 (2011).","journal-title":"Am. J. Clin. Nutr."},{"key":"1187_CR36","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1101\/gad.346312.120","volume":"35","author":"YS Lee","year":"2021","unstructured":"Lee, Y. S. & Olefsky, J. Chronic tissue inflammation and metabolic disease. Genes Dev. 35, 307\u2013328 (2021).","journal-title":"Genes Dev."},{"key":"1187_CR37","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1016\/S2468-1253(23)00272-8","volume":"8","author":"SA Harrison","year":"2023","unstructured":"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\u20131093 (2023).","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"1187_CR38","doi-asserted-by":"crossref","unstructured":"Friedman, L. M., Furberg, C. D., DeMets, D. L., Reboussin, D. M. & Granger, C. B. Fundamentals of Clinical Trials (Springer, 2015).","DOI":"10.1007\/978-3-319-18539-2"},{"key":"1187_CR39","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1093\/advances\/nmaa168","volume":"12","author":"SG O\u2019Connor","year":"2021","unstructured":"O\u2019Connor, S. G. et al. Perspective: time-restricted eating compared with caloric restriction: potential facilitators and barriers of long-term weight loss maintenance. Adv. Nutr. 12, 325\u2013333 (2021).","journal-title":"Adv. Nutr."},{"key":"1187_CR40","doi-asserted-by":"publisher","first-page":"2031","DOI":"10.1001\/jama.2021.19569","volume":"326","author":"A Aminian","year":"2021","unstructured":"Aminian, A. et al. Association of bariatric surgery with major adverse liver and cardiovascular outcomes in patients with biopsy-proven nonalcoholic steatohepatitis. JAMA 326, 2031\u20132042 (2021).","journal-title":"JAMA"},{"key":"1187_CR41","doi-asserted-by":"publisher","first-page":"988","DOI":"10.1038\/s41591-024-03480-y","volume":"31","author":"A Aminian","year":"2025","unstructured":"Aminian, A. et al. Long-term liver outcomes after metabolic surgery in compensated cirrhosis due to metabolic dysfunction-associated steatohepatitis. Nat. Med. 31, 988\u2013995 (2025).","journal-title":"Nat. Med."},{"key":"1187_CR42","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1016\/j.jhep.2024.04.031","volume":"81","author":"F Tacke","year":"2024","unstructured":"Tacke, F. et al. EASL\u2013EASD\u2013EASO clinical practice guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J. Hepatol. 81, 492\u2013542 (2024).","journal-title":"J. Hepatol."},{"key":"1187_CR43","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1055\/s-0041-1723751","volume":"41","author":"T Kawaguchi","year":"2021","unstructured":"Kawaguchi, T. et al. Effects of Mediterranean diet in patients with nonalcoholic fatty liver disease: a systematic review, meta-analysis, and meta-regression analysis of randomized controlled trials. Semin. Liver Dis. 41, 225\u2013234 (2021).","journal-title":"Semin. Liver Dis."},{"key":"1187_CR44","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-51470-4","volume":"14","author":"Y Xue","year":"2024","unstructured":"Xue, Y. et al. Effect of different exercise modalities on nonalcoholic fatty liver disease: a systematic review and network meta-analysis. Sci. Rep. 14, 6212 (2024).","journal-title":"Sci. Rep."},{"key":"1187_CR45","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2019-029966","volume":"9","author":"N Singh","year":"2019","unstructured":"Singh, N., Stewart, R. A. H. & Benatar, J. R. Intensity and duration of lifestyle interventions for long-term weight loss and association with mortality: a meta-analysis of randomised trials. BMJ Open\u00a09, e029966 (2019).","journal-title":"BMJ Open"},{"key":"1187_CR46","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1001\/jama.2020.12567","volume":"324","author":"DE Arterburn","year":"2020","unstructured":"Arterburn, D. E., Telem, D. A., Kushner, R. F. & Courcoulas, A. P. Benefits and risks of bariatric surgery in adults: a review. JAMA 324, 879\u2013887 (2020).","journal-title":"JAMA"},{"key":"1187_CR47","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1016\/j.cgh.2018.10.017","volume":"17","author":"Y Lee","year":"2019","unstructured":"Lee, Y. et al. Complete resolution of nonalcoholic fatty liver disease after bariatric surgery: a systematic review and meta-analysis. Clin. Gastroenterol. Hepatol. 17, 1040\u20131060.e11 (2019).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"1187_CR48","doi-asserted-by":"publisher","first-page":"1720","DOI":"10.2337\/dbi17-0007","volume":"67","author":"N Bozadjieva","year":"2018","unstructured":"Bozadjieva, N., Heppner, K. M. & Seeley, R. J. Targeting FXR and FGF19 to treat metabolic diseases \u2014 lessons learned from bariatric surgery. Diabetes 67, 1720\u20131728 (2018).","journal-title":"Diabetes"},{"key":"1187_CR49","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1007\/s13679-019-00334-4","volume":"8","author":"MG Browning","year":"2019","unstructured":"Browning, M. G., Pessoa, B. M., Khoraki, J. & Campos, G. M. Changes in bile acid metabolism, transport, and signaling as central drivers for metabolic improvements after bariatric surgery. Curr. Obes. Rep. 8, 175\u2013184 (2019).","journal-title":"Curr. Obes. Rep."},{"key":"1187_CR50","doi-asserted-by":"publisher","DOI":"10.1097\/HC9.0000000000000615","volume":"9","author":"M Ren","year":"2025","unstructured":"Ren, M. et al. Duodenal-jejunal bypass ameliorates MASLD in rats by regulating gut microbiota and bile acid metabolism through FXR pathways. Hepatol. Commun. 9, e0615 (2025).","journal-title":"Hepatol. Commun."},{"key":"1187_CR51","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.1053\/j.gastro.2020.06.006","volume":"159","author":"G Lassailly","year":"2020","unstructured":"Lassailly, G. et al. Bariatric surgery provides long-term resolution of nonalcoholic steatohepatitis and regression of fibrosis. Gastroenterology 159, 1290\u20131301.e5 (2020).","journal-title":"Gastroenterology"},{"key":"1187_CR52","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1056\/NEJMoa1700459","volume":"377","author":"TD Adams","year":"2017","unstructured":"Adams, T. D. et al. Weight and metabolic outcomes 12 years after gastric bypass. N. Engl. J. Med. 377, 1143\u20131155 (2017).","journal-title":"N. Engl. J. Med."},{"key":"1187_CR53","doi-asserted-by":"publisher","first-page":"1567","DOI":"10.1016\/j.cgh.2024.10.025","volume":"23","author":"G Lassailly","year":"2025","unstructured":"Lassailly, G. et al. Resolution of metabolic dysfunction-associated steatohepatitis with no worsening of fibrosis after bariatric surgery improves 15-year survival: a prospective cohort study. Clin. Gastroenterol. Hepatol. 23, 1567\u20131576.e9 (2025).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"1187_CR54","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s11695-022-06332-1","volume":"33","author":"D Eisenberg","year":"2023","unstructured":"Eisenberg, D. et al. 2022 American Society of Metabolic and Bariatric Surgery (ASMBS) and International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) indications for metabolic and bariatric surgery. Obes. Surg. 33, 3\u201314 (2023).","journal-title":"Obes. Surg."},{"key":"1187_CR55","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1016\/j.soard.2024.05.009","volume":"20","author":"M De Luca","year":"2024","unstructured":"De Luca, M. et al. Scientific evidence for the updated guidelines on indications for metabolic and bariatric surgery (IFSO\/ASMBS). Surg. Obes. Relat. Dis. 20, 991\u20131025 (2024).","journal-title":"Surg. Obes. Relat. Dis."},{"key":"1187_CR56","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1016\/j.amjmed.2025.01.021","volume":"138","author":"A Moiz","year":"2025","unstructured":"Moiz, A. et al. Mechanisms of GLP-1 receptor agonist-induced weight loss: a review of central and peripheral pathways in appetite and energy regulation. Am. J. Med. 138, 934\u2013940 (2025).","journal-title":"Am. J. Med."},{"key":"1187_CR57","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqae167","volume":"166","author":"LA Jones","year":"2025","unstructured":"Jones, L. A. & Brierley, D. I. GLP-1 and the neurobiology of eating control: recent advances. Endocrinology 166, bqae167 (2025).","journal-title":"Endocrinology"},{"key":"1187_CR58","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.14309\/ajg.0000000000002820","volume":"119","author":"B Hiramoto","year":"2024","unstructured":"Hiramoto, B. et al. Quantified metrics of gastric emptying delay by glucagon-like peptide-1 agonists: a systematic review and meta-analysis with insights for periprocedural management. Am. J. Gastroenterol. 119, 1126\u20131140 (2024).","journal-title":"Am. J. Gastroenterol."},{"key":"1187_CR59","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1111\/j.1463-1326.2012.01663.x","volume":"15","author":"AR Meloni","year":"2013","unstructured":"Meloni, A. R., DeYoung, M. B., Lowe, C. & Parkes, D. G. GLP-1 receptor activated insulin secretion from pancreatic \u03b2-cells: mechanism and glucose dependence. Diabetes Obes. Metab. 15, 15\u201327 (2013).","journal-title":"Diabetes Obes. Metab."},{"key":"1187_CR60","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.13852","volume":"6","author":"R Ramracheya","year":"2018","unstructured":"Ramracheya, R. et al. GLP-1 suppresses glucagon secretion in human pancreatic alpha-cells by inhibition of P\/Q-type Ca2+ channels. Physiol. Rep. 6, e13852 (2018).","journal-title":"Physiol. Rep."},{"key":"1187_CR61","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.jhep.2015.08.038","volume":"64","author":"MJ Armstrong","year":"2016","unstructured":"Armstrong, M. J. et al. Glucagon-like peptide 1 decreases lipotoxicity in non-alcoholic steatohepatitis. J. Hepatol. 64, 399\u2013408 (2016).","journal-title":"J. Hepatol."},{"key":"1187_CR62","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.bbalip.2018.12.010","volume":"1864","author":"D Alvares","year":"2019","unstructured":"Alvares, D., Hoffman, S., Stankovic, B. & Adeli, K. Gut peptide and neuroendocrine regulation of hepatic lipid and lipoprotein metabolism in health and disease. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1864, 326\u2013334 (2019).","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"1187_CR63","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1148209","volume":"14","author":"SF Mehdi","year":"2023","unstructured":"Mehdi, S. F. et al. Glucagon-like peptide-1: a multi-faceted anti-inflammatory agent. Front. Immunol. 14, 1148209 (2023).","journal-title":"Front. Immunol."},{"key":"1187_CR64","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00672","volume":"9","author":"J Rowlands","year":"2018","unstructured":"Rowlands, J., Heng, J., Newsholme, P. & Carlessi, R. Pleiotropic effects of GLP-1 and analogs on cell signaling, metabolism, and function. Front. Endocrinol. 9, 672 (2018).","journal-title":"Front. Endocrinol."},{"key":"1187_CR65","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102849","volume":"66","author":"C Luna-Marco","year":"2023","unstructured":"Luna-Marco, C. et al. Effects of GLP-1 receptor agonists on mitochondrial function, inflammatory markers and leukocyte-endothelium interactions in type 2 diabetes. Redox Biol. 66, 102849 (2023).","journal-title":"Redox Biol."},{"key":"1187_CR66","doi-asserted-by":"publisher","first-page":"3128","DOI":"10.1038\/s41591-025-03799-0","volume":"31","author":"M Jara","year":"2025","unstructured":"Jara, M. et al. Modulation of metabolic, inflammatory and fibrotic pathways by semaglutide in metabolic dysfunction-associated steatohepatitis. Nat. Med. 31, 3128\u20133140 (2025).","journal-title":"Nat. Med."},{"key":"1187_CR67","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1016\/S0168-8278(25)00314-9","volume":"82","author":"P Newsome","year":"2025","unstructured":"Newsome, P. et al. Weight-dependent and independent effects of semaglutide in participants with MASH: secondary analysis of the phase 3 ESSENCE trial [abstract 0010]. Hepatology 82, S11\u2013S13 (2025).","journal-title":"Hepatology"},{"key":"1187_CR68","doi-asserted-by":"publisher","first-page":"1834","DOI":"10.1056\/NEJMoa1607141","volume":"375","author":"SP Marso","year":"2016","unstructured":"Marso, S. P. et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N. Engl. J. Med. 375, 1834\u20131844 (2016).","journal-title":"N. Engl. J. Med."},{"key":"1187_CR69","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1056\/NEJMoa1603827","volume":"375","author":"SP Marso","year":"2016","unstructured":"Marso, S. P. et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 375, 311\u2013322 (2016).","journal-title":"N. Engl. J. Med."},{"key":"1187_CR70","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1136\/gutjnl-2024-334591","volume":"74","author":"C Celsa","year":"2025","unstructured":"Celsa, C. et al. Glucagon-like peptide-1 receptor agonist use is associated with a lower risk of major adverse liver-related outcomes: a meta-analysis of observational cohort studies. Gut 74, 815\u2013824 (2025).","journal-title":"Gut"},{"key":"1187_CR71","doi-asserted-by":"publisher","first-page":"1534","DOI":"10.1016\/j.cmet.2024.05.010","volume":"36","author":"A Regmi","year":"2024","unstructured":"Regmi, A. et al. Tirzepatide modulates the regulation of adipocyte nutrient metabolism through long-acting activation of the GIP receptor. Cell Metab. 36, 1534\u20131549.e7 (2024).","journal-title":"Cell Metab."},{"key":"1187_CR72","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1431292","volume":"15","author":"QK Liu","year":"2024","unstructured":"Liu, Q. K. Mechanisms of action and therapeutic applications of GLP-1 and dual GIP\/GLP-1 receptor agonists. Front. Endocrinol. 15, 1431292 (2024).","journal-title":"Front. Endocrinol."},{"key":"1187_CR73","doi-asserted-by":"publisher","first-page":"2545","DOI":"10.2337\/db21-0459","volume":"70","author":"T Borner","year":"2021","unstructured":"Borner, T. et al. GIP receptor agonism attenuates GLP-1 receptor agonist-induced nausea and emesis in preclinical models. Diabetes 70, 2545\u20132553 (2021).","journal-title":"Diabetes"},{"key":"1187_CR74","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00413","volume":"10","author":"KD Galsgaard","year":"2019","unstructured":"Galsgaard, K. D., Pedersen, J., Knop, F. K., Holst, J. J. & Wewer Albrechtsen, N. J. Glucagon receptor signaling and lipid metabolism. Front. Physiol. 10, 413 (2019).","journal-title":"Front. Physiol."},{"key":"1187_CR75","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1002\/oby.23633","volume":"31","author":"KD Corbin","year":"2023","unstructured":"Corbin, K. D. et al. Glucagon-like peptide-1\/glucagon receptor agonism associates with reduced metabolic adaptation and higher fat oxidation: a randomized trial. Obesity 31, 350\u2013362 (2023).","journal-title":"Obesity"},{"key":"1187_CR76","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.735019","volume":"12","author":"DCD Hope","year":"2021","unstructured":"Hope, D. C. D., Vincent, M. L. & Tan, T. M. M. Striking the balance: GLP-1\/glucagon co-agonism as a treatment strategy for obesity. Front. Endocrinol. 12, 735019 (2021).","journal-title":"Front. Endocrinol."},{"key":"1187_CR77","first-page":"860","volume":"30","author":"PP Gleason","year":"2024","unstructured":"Gleason, P. P. et al. Real-world persistence and adherence to glucagon-like peptide-1 receptor agonists among obese commercially insured adults without diabetes. J. Manag. Care Spec. Pharm. 30, 860\u2013867 (2024).","journal-title":"J. Manag. Care Spec. Pharm."},{"key":"1187_CR78","doi-asserted-by":"publisher","first-page":"1553","DOI":"10.1111\/dom.14725","volume":"24","author":"JPH Wilding","year":"2022","unstructured":"Wilding, J. P. H. et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension. Diabetes Obes. Metab. 24, 1553\u20131564 (2022).","journal-title":"Diabetes Obes. Metab."},{"key":"1187_CR79","first-page":"351","volume":"28","author":"AM Chavez","year":"2025","unstructured":"Chavez, A. M., Carrasco Barria, R. & Le\u00f3n-Sanz, M. Nutrition support whilst on glucagon-like peptide-1 based therapy. Is it necessary? Curr. Opin. Clin. Nutr. Metab. Care 28, 351\u2013357 (2025).","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"1187_CR80","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/j.jhep.2024.10.018","volume":"82","author":"V Ratziu","year":"2025","unstructured":"Ratziu, V., Scanlan, T. S. & Bruinstroop, E. Thyroid hormone receptor-\u03b2 analogues for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). J. Hepatol. 82, 375\u2013387 (2025).","journal-title":"J. Hepatol."},{"key":"1187_CR81","doi-asserted-by":"publisher","DOI":"10.3390\/cells12242806","volume":"12","author":"R Ramanathan","year":"2023","unstructured":"Ramanathan, R., Patwa, S. A., Ali, A. H. & Ibdah, J. A. Thyroid hormone and mitochondrial dysfunction: therapeutic implications for metabolic dysfunction-associated steatotic liver disease (MASLD). Cells 12, 2806 (2023).","journal-title":"Cells"},{"key":"1187_CR82","doi-asserted-by":"publisher","DOI":"10.1038\/s44324-024-00022-5","volume":"2","author":"S Raza","year":"2024","unstructured":"Raza, S., Rajak, S., Yen, P. M. & Sinha, R. A. Autophagy and hepatic lipid metabolism: mechanistic insight and therapeutic potential for MASLD. npj\u00a0Metab. Health Dis. 2, 19 (2024).","journal-title":"npj\u00a0Metab. Health Dis."},{"key":"1187_CR83","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1089\/thy.2007.0288","volume":"18","author":"MO Ribeiro","year":"2008","unstructured":"Ribeiro, M. O. Effects of thyroid hormone analogs on lipid metabolism and thermogenesis. Thyroid 18, 197\u2013203 (2008).","journal-title":"Thyroid"},{"key":"1187_CR84","doi-asserted-by":"publisher","first-page":"3284","DOI":"10.1021\/acs.jmedchem.2c01669","volume":"66","author":"L Hu","year":"2023","unstructured":"Hu, L. et al. Discovery of highly potent and selective thyroid hormone receptor \u03b2 agonists for the treatment of nonalcoholic steatohepatitis. J. Med. Chem. 66, 3284\u20133300 (2023).","journal-title":"J. Med. Chem."},{"key":"1187_CR85","doi-asserted-by":"publisher","DOI":"10.3390\/cells14080580","volume":"14","author":"B Polini","year":"2025","unstructured":"Polini, B. et al. Novel thyroid hormone receptor-\u03b2 agonist TG68 exerts anti-inflammatory, lipid-lowering and anxiolytic effects in a high-fat diet (HFD) mouse model of obesity. Cells 14, 580 (2025).","journal-title":"Cells"},{"key":"1187_CR86","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1089\/thy.2021.0621","volume":"32","author":"J Zhou","year":"2022","unstructured":"Zhou, J. et al. Thyroid hormone decreases hepatic steatosis, inflammation, and fibrosis in a dietary mouse model of nonalcoholic steatohepatitis. Thyroid 32, 725\u2013738 (2022).","journal-title":"Thyroid"},{"key":"1187_CR87","doi-asserted-by":"publisher","first-page":"2134","DOI":"10.1038\/s41401-024-01303-x","volume":"45","author":"K Sun","year":"2024","unstructured":"Sun, K. et al. A new mechanism of thyroid hormone receptor \u03b2 agonists ameliorating nonalcoholic steatohepatitis by inhibiting intestinal lipid absorption via remodeling bile acid profiles. Acta Pharmacol. Sin. 45, 2134\u20132148 (2024).","journal-title":"Acta Pharmacol. Sin."},{"key":"1187_CR88","doi-asserted-by":"publisher","DOI":"10.2337\/db24-760-P","volume":"73","author":"C JONES","year":"2024","unstructured":"JONES, C. et al. TERN-501 enhances weight loss efficacy of a GLP-1R agonist in obese mice via increased fat mass loss without additional loss of lean mass [abstract]. Diabetes 73, 760-P (2024).","journal-title":"Diabetes"},{"key":"1187_CR89","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1016\/j.jhep.2024.04.034","volume":"81","author":"SA Harrison","year":"2024","unstructured":"Harrison, S. A., Rolph, T., Knott, M. & Dubourg, J. FGF21 agonists: an emerging therapeutic for metabolic dysfunction-associated steatohepatitis and beyond. J. Hepatol. 81, 562\u2013576 (2024).","journal-title":"J. Hepatol."},{"key":"1187_CR90","doi-asserted-by":"publisher","first-page":"1532","DOI":"10.2337\/db08-1775","volume":"58","author":"K Mai","year":"2009","unstructured":"Mai, K. et al. Free fatty acids link metabolism and regulation of the insulin-sensitizing fibroblast growth factor-21. Diabetes 58, 1532\u20131538 (2009).","journal-title":"Diabetes"},{"key":"1187_CR91","doi-asserted-by":"publisher","first-page":"3230","DOI":"10.1016\/j.febslet.2009.09.012","volume":"583","author":"X Li","year":"2009","unstructured":"Li, X. et al. Inhibition of lipolysis may contribute to the acute regulation of plasma FFA and glucose by FGF21 in ob\/ob mice. FEBS Lett. 583, 3230\u20133234 (2009).","journal-title":"FEBS Lett."},{"key":"1187_CR92","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1016\/j.jsbmb.2013.08.013","volume":"138","author":"H Chen","year":"2013","unstructured":"Chen, H. et al. Adiponectin activates the AMPK signaling pathway to regulate lipid metabolism in bovine hepatocytes. J. Steroid Biochem. Mol. Biol. 138, 445\u2013454 (2013).","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"1187_CR93","doi-asserted-by":"publisher","first-page":"2562","DOI":"10.2337\/db05-1322","volume":"55","author":"MJ Yoon","year":"2006","unstructured":"Yoon, M. J. et al. Adiponectin increases fatty acid oxidation in skeletal muscle cells by sequential activation of AMP-activated protein kinase, p38 mitogen-activated protein kinase, and peroxisome proliferator-activated receptor alpha. Diabetes 55, 2562\u20132570 (2006).","journal-title":"Diabetes"},{"key":"1187_CR94","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1056\/NEJMoa2304286","volume":"389","author":"R Loomba","year":"2023","unstructured":"Loomba, R. et al. Randomized, controlled trial of the FGF21 analogue pegozafermin in NASH. N. Engl. J. Med. 389, 998\u20131008 (2023).","journal-title":"N. Engl. J. Med."},{"key":"1187_CR95","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14384-z","volume":"11","author":"S Byun","year":"2020","unstructured":"Byun, S. et al. Fasting-induced FGF21 signaling activates hepatic autophagy and lipid degradation via JMJD3 histone demethylase. Nat. Commun. 11, 807 (2020).","journal-title":"Nat. Commun."},{"key":"1187_CR96","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2023.05.019","volume":"11","author":"W Shen","year":"2024","unstructured":"Shen, W. et al. FGF21-mediated autophagy: remodeling the homeostasis in response to stress in liver diseases. Genes Dis. 11, 101027 (2024).","journal-title":"Genes Dis."},{"key":"1187_CR97","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.taap.2015.11.012","volume":"290","author":"P Xu","year":"2016","unstructured":"Xu, P. et al. Fibroblast growth factor 21 attenuates hepatic fibrogenesis through TGF-\u03b2\/smad2\/3 and NF-\u03baB signaling pathways. Toxicol. Appl. Pharmacol. 290, 43\u201353 (2016).","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"1187_CR98","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/5042762","volume":"2022","author":"MQ Jia","year":"2022","unstructured":"Jia, M. Q., Guan, C. X., Tao, J. H. & Zhou, Y. Research progress of fibroblast growth factor 21 in fibrotic diseases. Oxid. Med. Cell Longev. 2022, 5042762 (2022).","journal-title":"Oxid. Med. Cell Longev."},{"key":"1187_CR99","doi-asserted-by":"publisher","first-page":"2413","DOI":"10.1056\/NEJMoa2502242","volume":"392","author":"M Noureddin","year":"2025","unstructured":"Noureddin, M. et al. Efruxifermin in compensated liver cirrhosis caused by MASH. N. Engl. J. Med. 392, 2413\u20132424 (2025).","journal-title":"N. Engl. J. Med."},{"key":"1187_CR100","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1016\/S0140-6736(25)01073-6","volume":"406","author":"M Noureddin","year":"2025","unstructured":"Noureddin, M. et al. Safety and efficacy of once-weekly efruxifermin versus placebo in metabolic dysfunction-associated steatohepatitis (HARMONY): 96-week results from a multicentre, randomised, double-blind, placebo-controlled, phase 2b trial. Lancet 406, 719\u2013730 (2025).","journal-title":"Lancet"},{"key":"1187_CR101","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1016\/S0140-6736(25)02276-7","volume":"407","author":"M Noureddin","year":"2026","unstructured":"Noureddin, M. et al.\u00a0Efimosfermin alfa (BOS-580) once per month in people with metabolic dysfunction-associated steatohepatitis with F2 or F3 fibrosis: results from a 24-week, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet\u00a0407, 794\u2013804 (2026).","journal-title":"Lancet"},{"key":"1187_CR102","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/j.cmet.2019.01.004","volume":"29","author":"SA Kliewer","year":"2019","unstructured":"Kliewer, S. A. & Mangelsdorf, D. J. A dozen years of discovery: insights into the physiology and pharmacology of FGF21. Cell Metab. 29, 246\u2013253 (2019).","journal-title":"Cell Metab."},{"key":"1187_CR103","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1016\/j.cmet.2014.07.012","volume":"20","author":"BM Owen","year":"2014","unstructured":"Owen, B. M. et al. FGF21 acts centrally to induce sympathetic nerve activity, energy expenditure, and weight loss. Cell Metab. 20, 670\u2013677 (2014).","journal-title":"Cell Metab."},{"key":"1187_CR104","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1172\/JCI23621","volume":"115","author":"KL Donnelly","year":"2005","unstructured":"Donnelly, K. L. et al. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J. Clin. Invest. 115, 1343\u20131351 (2005).","journal-title":"J. Clin. Invest."},{"key":"1187_CR105","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1080\/13543784.2020.1668374","volume":"29","author":"N Alkhouri","year":"2020","unstructured":"Alkhouri, N., Lawitz, E., Noureddin, M., DeFronzo, R. & Shulman, G. I. GS-0976 (Firsocostat): an investigational liver-directed acetyl-CoA carboxylase (ACC) inhibitor for the treatment of non-alcoholic steatohepatitis (NASH). Expert Opin. Investig. Drugs 29, 135\u2013141 (2020).","journal-title":"Expert Opin. Investig. Drugs"},{"key":"1187_CR106","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1053\/j.gastro.2018.07.027","volume":"155","author":"R Loomba","year":"2018","unstructured":"Loomba, R. et al. GS-0976 reduces hepatic steatosis and fibrosis markers in patients with nonalcoholic fatty liver disease. Gastroenterology 155, 1463\u20131473.e6 (2018).","journal-title":"Gastroenterology"},{"key":"1187_CR107","doi-asserted-by":"publisher","first-page":"2197","DOI":"10.1002\/hep.30097","volume":"68","author":"L Goedeke","year":"2018","unstructured":"Goedeke, L. et al. Acetyl-CoA carboxylase inhibition reverses NAFLD and hepatic insulin resistance but promotes hypertriglyceridemia in rodents. Hepatology 68, 2197\u20132211 (2018).","journal-title":"Hepatology"},{"key":"1187_CR108","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/j.molmet.2015.03.004","volume":"4","author":"G Solinas","year":"2015","unstructured":"Solinas, G., Bor\u00e9n, J. & Dulloo, A. G. De novo lipogenesis in metabolic homeostasis: more friend than foe?\u00a0Mol. Metab. 4, 367\u2013377 (2015).","journal-title":"Mol. Metab."},{"key":"1187_CR109","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.1016\/S2468-1253(24)00246-2","volume":"9","author":"R Loomba","year":"2024","unstructured":"Loomba, R. et al. Denifanstat for the treatment of metabolic dysfunction-associated steatohepatitis: a multicentre, double-blind, randomised, placebo-controlled, phase 2b trial. Lancet Gastroenterol. Hepatol. 9, 1090\u20131100 (2024).","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"1187_CR110","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1097\/HEP.0000000000000980","volume":"81","author":"V Ratziu","year":"2025","unstructured":"Ratziu, V. et al. Aramchol improves hepatic fibrosis in metabolic dysfunction-associated steatohepatitis: results of multimodality assessment using both conventional and digital pathology. Hepatology 81, 932\u2013946 (2025).","journal-title":"Hepatology"},{"key":"1187_CR111","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1016\/S0140-6736(25)00979-1","volume":"406","author":"R Loomba","year":"2025","unstructured":"Loomba, R. et al. Antisense oligonucleotide DGAT-2 inhibitor, ION224, for metabolic dysfunction-associated steatohepatitis (ION224-CS2): results of a 51-week, multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet 406, 821\u2013831 (2025).","journal-title":"Lancet"},{"key":"1187_CR112","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1016\/S2468-1253(25)00128-1","volume":"10","author":"VW Wong","year":"2025","unstructured":"Wong, V. W. et al. Efficacy and safety of ervogastat alone and in combination with clesacostat in patients with biopsy-confirmed metabolic dysfunction-associated steatohepatitis and F2-F3 fibrosis (MIRNA): results from a phase 2, randomised, double-blind, double-dummy study. Lancet Gastroenterol. Hepatol. 10, 924\u2013940 (2025).","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"1187_CR113","doi-asserted-by":"publisher","first-page":"1366","DOI":"10.1002\/hep.21655","volume":"45","author":"K Yamaguchi","year":"2007","unstructured":"Yamaguchi, K. et al. Inhibiting triglyceride synthesis improves hepatic steatosis but exacerbates liver damage and fibrosis in obese mice with nonalcoholic steatohepatitis. Hepatology 45, 1366\u20131374 (2007).","journal-title":"Hepatology"},{"key":"1187_CR114","doi-asserted-by":"publisher","DOI":"10.3390\/cells9010037","volume":"9","author":"J Boeckmans","year":"2019","unstructured":"Boeckmans, J. et al. Anti-NASH drug development hitches a lift on PPAR agonism. Cells 9, 37 (2019).","journal-title":"Cells"},{"key":"1187_CR115","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000031508","volume":"101","author":"Y Zhao","year":"2022","unstructured":"Zhao, Y. et al. Pioglitazone on nonalcoholic steatohepatitis: a systematic review and meta-analysis of 15 RCTs. Medicine 101, e31508 (2022).","journal-title":"Medicine"},{"key":"1187_CR116","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1016\/j.jhep.2023.02.004","volume":"78","author":"SA Harrison","year":"2023","unstructured":"Harrison, S. A. et al. Evaluation of PXL065 \u2014 deuterium-stabilized (R)-pioglitazone in patients with NASH: a phase II randomized placebo-controlled trial (DESTINY-1). J. Hepatol. 78, 914\u2013925 (2023).","journal-title":"J. Hepatol."},{"key":"1187_CR117","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1056\/NEJMoa2036205","volume":"385","author":"SM Francque","year":"2021","unstructured":"Francque, S. M. et al. A randomized, controlled trial of the pan-PPAR agonist lanifibranor in NASH. N. Engl. J. Med. 385, 1547\u20131558 (2021).","journal-title":"N. Engl. J. Med."},{"key":"1187_CR118","unstructured":"Harrison, S. A. RESOLVE-IT phase 3 trial of elafibranor in NASH: final results of the week 72 interim surrogate efficacy analysis. Presented at the AASLD Liver Meeting (2020)."},{"key":"1187_CR119","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.179990","volume":"10","author":"E Holm","year":"2025","unstructured":"Holm, E. et al. AMPK activator ATX-304 reduces oxidative stress and improves MASLD via metabolic switching. JCI Insight 10, e179990 (2025).","journal-title":"JCI Insight"},{"key":"1187_CR120","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1016\/S2468-1253(21)00300-9","volume":"6","author":"K Cusi","year":"2021","unstructured":"Cusi, K. et al. Efficacy and safety of PXL770, a direct AMP kinase activator, for the treatment of non-alcoholic fatty liver disease (STAMP-NAFLD): a randomised, double-blind, placebo-controlled, phase 2a study. Lancet Gastroenterol. Hepatol. 6, 889\u2013902 (2021).","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"1187_CR121","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2021.100474","volume":"2","author":"P Fouqueray","year":"2021","unstructured":"Fouqueray, P. et al. Pharmacodynamic effects of direct AMP kinase activation in humans with insulin resistance and non-alcoholic fatty liver disease: a phase 1b study. Cell Rep. Med. 2, 100474 (2021).","journal-title":"Cell Rep. Med."},{"key":"1187_CR122","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2025.107706","volume":"215","author":"M Zhang","year":"2025","unstructured":"Zhang, M. et al. Dual inhibition of hepatic ACLY and ACSS2: a synergistic approach to combat NAFLD through lipogenesis reduction and mitochondrial enhancement. Pharmacol. Res. 215, 107706 (2025).","journal-title":"Pharmacol. Res."},{"key":"1187_CR123","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/S2213-8587(24)00318-8","volume":"13","author":"N Stefan","year":"2025","unstructured":"Stefan, N., Yki-J\u00e4rvinen, H. & Neuschwander-Tetri, B. A. Metabolic dysfunction-associated steatotic liver disease: heterogeneous pathomechanisms and effectiveness of metabolism-based treatment. Lancet Diabetes Endocrinol. 13, 134\u2013148 (2025).","journal-title":"Lancet Diabetes Endocrinol."},{"key":"1187_CR124","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1038\/ng.2926","volume":"46","author":"OL Holmen","year":"2014","unstructured":"Holmen, O. L. et al. Systematic evaluation of coding variation identifies a candidate causal variant in TM6SF2 influencing total cholesterol and myocardial infarction risk. Nat. Genet. 46, 345\u2013351 (2014).","journal-title":"Nat. Genet."},{"key":"1187_CR125","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1053\/j.gastro.2016.12.020","volume":"152","author":"N Simons","year":"2017","unstructured":"Simons, N. et al. PNPLA3, TM6SF2, and MBOAT7 genotypes and coronary artery disease. Gastroenterology 152, 912\u2013913 (2017).","journal-title":"Gastroenterology"},{"key":"1187_CR126","doi-asserted-by":"crossref","first-page":"S1565","DOI":"10.1097\/HEP.0000000000000896","volume":"80","author":"N Chalasani","year":"2024","unstructured":"Chalasani, N., Labriola, D., Taub, R. & Anstee, Q. Resmetirom effects on NASH with liver fibrosis in patients with NASH genetic risk alleles [abstract 2070]. Hepatology 80, S1565\u2013S1566 (2024).","journal-title":"Hepatology"},{"key":"1187_CR127","unstructured":"Sanyal, A. Impact of PNPLA3 rs738409 variant on the response to tirzepatide versus placebo for the treatment of non-cirrhotic MASH. Presented at the AASLD Liver Meeting, Abstract 5014 (2024)."},{"key":"1187_CR128","doi-asserted-by":"publisher","first-page":"2177","DOI":"10.1016\/j.cgh.2024.05.052","volume":"22","author":"S Sookoian","year":"2024","unstructured":"Sookoian, S., Rotman, Y. & Valenti, L. Genetics of metabolic dysfunction-associated steatotic liver disease: the state of the art update. Clin. Gastroenterol. Hepatol. 22, 2177\u20132187.e3 (2024).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"1187_CR129","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1055\/s-0041-1730927","volume":"41","author":"M Arrese","year":"2021","unstructured":"Arrese, M. et al. Insights into nonalcoholic fatty-liver disease heterogeneity. Semin. Liver Dis. 41, 421\u2013434 (2021).","journal-title":"Semin. Liver Dis."},{"key":"1187_CR130","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1080\/17474124.2023.2191190","volume":"17","author":"CJ Pirola","year":"2023","unstructured":"Pirola, C. J. & Sookoian, S. Advances in our understanding of the molecular heterogeneity of fatty liver disease: toward informed treatment decision making. Expert Rev. Gastroenterol. Hepatol. 17, 317\u2013324 (2023).","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"1187_CR131","doi-asserted-by":"publisher","first-page":"461","DOI":"10.3350\/cmh.2020.0136","volume":"26","author":"S Sookoian","year":"2020","unstructured":"Sookoian, S. & Pirola, C. J. Precision medicine in nonalcoholic fatty liver disease: new therapeutic insights from genetics and systems biology. Clin. Mol. Hepatol. 26, 461\u2013475 (2020).","journal-title":"Clin. Mol. Hepatol."},{"key":"1187_CR132","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.1038\/ng.257","volume":"40","author":"S Romeo","year":"2008","unstructured":"Romeo, S. et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat. Genet. 40, 1461\u20131465 (2008).","journal-title":"Nat. Genet."},{"key":"1187_CR133","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1038\/ng.2901","volume":"46","author":"J Kozlitina","year":"2014","unstructured":"Kozlitina, J. et al. Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease. Nat. Genet. 46, 352\u2013356 (2014).","journal-title":"Nat. Genet."},{"key":"1187_CR134","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1056\/NEJMoa1712191","volume":"378","author":"NS Abul-Husn","year":"2018","unstructured":"Abul-Husn, N. S. et al. A protein-truncating HSD17B13 variant and protection from chronic liver disease. N. Engl. J. Med. 378, 1096\u20131106 (2018).","journal-title":"N. Engl. J. Med."},{"key":"1187_CR135","doi-asserted-by":"publisher","first-page":"1883","DOI":"10.1002\/hep.24283","volume":"53","author":"S Sookoian","year":"2011","unstructured":"Sookoian, S. & Pirola, C. J. Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease. Hepatology 53, 1883\u20131894 (2011).","journal-title":"Hepatology"},{"key":"1187_CR136","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1194\/jlr.P089953","volume":"60","author":"CJ Pirola","year":"2019","unstructured":"Pirola, C. J. et al. Splice variant rs72613567 prevents worst histologic outcomes in patients with nonalcoholic fatty liver disease. J. Lipid Res. 60, 176\u2013185 (2019).","journal-title":"J. Lipid Res."},{"key":"1187_CR137","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1053\/j.gastro.2013.07.047","volume":"145","author":"SK Murphy","year":"2013","unstructured":"Murphy, S. K. et al. Relationship between methylome and transcriptome in patients with nonalcoholic fatty liver disease. Gastroenterology 145, 1076\u20131087 (2013).","journal-title":"Gastroenterology"},{"key":"1187_CR138","doi-asserted-by":"publisher","first-page":"1992","DOI":"10.1002\/hep.23927","volume":"52","author":"S Sookoian","year":"2010","unstructured":"Sookoian, S. et al. Epigenetic regulation of insulin resistance in nonalcoholic fatty liver disease: impact of liver methylation of the peroxisome proliferator-activated receptor \u03b3 coactivator 1\u03b1 promoter. Hepatology 52, 1992\u20132000 (2010).","journal-title":"Hepatology"},{"key":"1187_CR139","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1136\/gutjnl-2016-311526","volume":"66","author":"T Hardy","year":"2017","unstructured":"Hardy, T. et al. Plasma DNA methylation: a potential biomarker for stratification of liver fibrosis in non-alcoholic fatty liver disease. Gut 66, 1321\u20131328 (2017).","journal-title":"Gut"},{"key":"1187_CR140","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.1136\/gutjnl-2012-302962","volume":"62","author":"CJ Pirola","year":"2013","unstructured":"Pirola, C. J. et al. Epigenetic modification of liver mitochondrial DNA is associated with histological severity of nonalcoholic fatty liver disease. Gut 62, 1356\u20131363 (2013).","journal-title":"Gut"},{"key":"1187_CR141","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101853","volume":"5","author":"EY Tan","year":"2024","unstructured":"Tan, E. Y., Muthiah, M. D. & Sanyal, A. J. Metabolomics at the cutting edge of risk prediction of MASLD. Cell Rep. Med. 5, 101853 (2024).","journal-title":"Cell Rep. Med."},{"key":"1187_CR142","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abk0855","volume":"14","author":"H Leung","year":"2022","unstructured":"Leung, H. et al. Risk assessment with gut microbiome and metabolite markers in NAFLD development. Sci. Transl. Med. 14, eabk0855 (2022).","journal-title":"Sci. Transl. Med."},{"key":"1187_CR143","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.1136\/gutjnl-2019-318811","volume":"69","author":"S Sookoian","year":"2020","unstructured":"Sookoian, S. et al. Intrahepatic bacterial metataxonomic signature in non-alcoholic fatty liver disease. Gut 69, 1483\u20131491 (2020).","journal-title":"Gut"},{"key":"1187_CR144","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1111\/apt.18468","volume":"61","author":"CJ Pirola","year":"2025","unstructured":"Pirola, C. J., Fern\u00e1ndez Gianotti, T. & Sookoian, S. The proteomics of MASLD progression: insights from functional analysis to drive the development of new therapeutic solutions. Aliment. Pharmacol. Ther. 61, 614\u2013627 (2025).","journal-title":"Aliment. Pharmacol. Ther."},{"key":"1187_CR145","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1038\/s41575-024-00915-2","volume":"21","author":"KP Matchett","year":"2024","unstructured":"Matchett, K. P., Paris, J., Teichmann, S. A. & Henderson, N. C. Spatial genomics: mapping human steatotic liver disease. Nat. Rev. Gastroenterol. Hepatol. 21, 646\u2013660 (2024).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"1187_CR146","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2021.100278","volume":"3","author":"VL Payen","year":"2021","unstructured":"Payen, V. L. et al. Single-cell RNA sequencing of human liver reveals hepatic stellate cell heterogeneity. JHEP Rep. 3, 100278 (2021).","journal-title":"JHEP Rep."},{"key":"1187_CR147","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2024.101223","volume":"7","author":"V Merens","year":"2025","unstructured":"Merens, V. et al. Hepatic stellate cell single cell atlas reveals a highly similar activation process across liver disease aetiologies. JHEP Rep. 7, 101223 (2025).","journal-title":"JHEP Rep."},{"key":"1187_CR148","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1038\/s42255-023-00775-1","volume":"5","author":"O Govaere","year":"2023","unstructured":"Govaere, O. et al. A proteo-transcriptomic map of non-alcoholic fatty liver disease signatures. Nat. Metab. 5, 572\u2013578 (2023).","journal-title":"Nat. Metab."},{"key":"1187_CR149","doi-asserted-by":"publisher","first-page":"1652","DOI":"10.1038\/s41588-022-01199-5","volume":"54","author":"G Sveinbjornsson","year":"2022","unstructured":"Sveinbjornsson, G. et al. Multiomics study of nonalcoholic fatty liver disease. Nat. Genet. 54, 1652\u20131663 (2022).","journal-title":"Nat. Genet."},{"key":"1187_CR150","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adh9940","volume":"16","author":"J Ding","year":"2024","unstructured":"Ding, J. et al. Integrative multiomic analysis identifies distinct molecular subtypes of NAFLD in a Chinese population. Sci. Transl. Med. 16, eadh9940 (2024).","journal-title":"Sci. Transl. Med."},{"key":"1187_CR151","doi-asserted-by":"publisher","first-page":"3614","DOI":"10.1038\/s41591-024-03284-0","volume":"30","author":"O Jamialahmadi","year":"2024","unstructured":"Jamialahmadi, O. et al. Partitioned polygenic risk scores identify distinct types of metabolic dysfunction-associated steatotic liver disease. Nat. Med. 30, 3614\u20133623 (2024).","journal-title":"Nat. Med."},{"key":"1187_CR152","doi-asserted-by":"publisher","first-page":"3624","DOI":"10.1038\/s41591-024-03283-1","volume":"30","author":"V Raverdy","year":"2024","unstructured":"Raverdy, V. et al. Data-driven cluster analysis identifies distinct types of metabolic dysfunction-associated steatotic liver disease. Nat. Med. 30, 3624\u20133633 (2024).","journal-title":"Nat. Med."},{"key":"1187_CR153","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2024.102184","volume":"35","author":"S Li","year":"2024","unstructured":"Li, S. et al. Oligonucleotide therapies for nonalcoholic steatohepatitis. Mol. Ther. Nucleic Acids 35, 102184 (2024).","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"1187_CR154","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1016\/j.jhepr.2019.09.002","volume":"1","author":"M Alves-Bezerra","year":"2019","unstructured":"Alves-Bezerra, M., Furey, N., Johnson, C. G. & Bissig, K. D. Using CRISPR\/Cas9 to model human liver disease. JHEP Rep. 1, 392\u2013402 (2019).","journal-title":"JHEP Rep."},{"key":"1187_CR155","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1016\/j.jhep.2024.10.044","volume":"82","author":"HY Kim","year":"2025","unstructured":"Kim, H. Y. et al. Multi-modal analysis of human hepatic stellate cells identifies novel therapeutic targets for metabolic dysfunction-associated steatotic liver disease. J. Hepatol. 82, 882\u2013897 (2025).","journal-title":"J. Hepatol."},{"key":"1187_CR156","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1093\/stcltm\/szad082","volume":"13","author":"F Korkida","year":"2024","unstructured":"Korkida, F., Stamatopoulou, A. & Roubelakis, M. G. Recent advances in mesenchymal stem\/stromal cell-based therapy for alcohol-associated liver disease and non-alcoholic fatty liver disease. Stem Cell Transl. Med. 13, 107\u2013115 (2024).","journal-title":"Stem Cell Transl. Med."},{"key":"1187_CR157","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.cobme.2019.01.001","volume":"9","author":"D Witt","year":"2019","unstructured":"Witt, D., Kellogg, R., Snyder, M. & Dunn, J. Windows into human health through wearables data analytics. Curr. Opin. Biomed. Eng. 9, 28\u201346 (2019).","journal-title":"Curr. Opin. Biomed. Eng."},{"key":"1187_CR158","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.jhep.2025.01.032","volume":"83","author":"SA Harrison","year":"2025","unstructured":"Harrison, S. A. et al. A phase IIb randomised-controlled trial of the FFAR1\/FFAR4 agonist icosabutate in MASH. J. Hepatol. 83, 293\u2013303 (2025).","journal-title":"J. Hepatol."}],"container-title":["Nature Reviews Gastroenterology &amp; Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41575-026-01187-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41575-026-01187-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41575-026-01187-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:02:07Z","timestamp":1780401727000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41575-026-01187-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,18]]},"references-count":158,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["1187"],"URL":"https:\/\/doi.org\/10.1038\/s41575-026-01187-8","relation":{},"ISSN":["1759-5045","1759-5053"],"issn-type":[{"value":"1759-5045","type":"print"},{"value":"1759-5053","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,18]]},"assertion":[{"value":"24 February 2026","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 March 2026","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"M.E.R. has provided scientific consulting for Akero, Altimmune, 89Bio, Boehringer Ingelheim, Intercept Pharmaceuticals, Histoindex, Madrigal, NGM Biopharmaceuticals, Novo Nordisk, Eli Lilly, Sagimet Biosciences, Sonic Incytes, Cytodyn, GSK, Regeneron and Roche. S.S. declares no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The authors acknowledge that papers authored by scholars from historically excluded groups are systematically under-cited. Every attempt has been made to reference relevant papers in a manner that is equitable in terms of racial, ethnic, gender and geographical representation.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Citation diversity statement"}}]}}