{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:40:52Z","timestamp":1792291252519,"version":"4.4.0"},"reference-count":62,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Metabolic dysfunction\u2010associated steatohepatitis (MASH) is a leading indication for liver transplantation, and fibrosis stage most strongly predicts clinical outcomes. Pharmacologic treatment is now available with resmetirom and semaglutide holding conditional approval.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To describe the therapeutic landscape for MASH with a focus on anti\u2010fibrotic impact.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Narrative review of Phase 2 and 3 trials, meta\u2010analyses, epidemiological data, and trial registries.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Historically, drugs targeting downstream fibrogenic or inflammatory pathways have had limited success in advanced development, whereas those improving metabolic dysfunction have had fared better. Fibrosis improvement by at least one stage was seen with resmetirom in up to 26% versus 14% placebo after 52\u2009weeks and with semaglutide in 37% versus 22% after 72\u2009weeks. Several agents in development (e.g., fibroblast growth factor 21 analogues, as well as dual and triple incretin agonists, pan\u2010peroxisome proliferator\u2010activated receptor agonist) report encouraging Phase 2 results, with Phase 3 trials ongoing. Compensated cirrhosis requires a distinct approach related to its fibrosis heterogeneity and burden of portal hypertension. This requires a delicate balance between efficacy and event rates that is further complicated by current regulatory constraints.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Fibrosis improvement in MASH is attainable by available drugs with further promise from emerging therapies. The link between treatment induced histological improvement or improvement in noninvasive tests and reduction in clinical outcomes remains unproven. A rich therapeutic pipeline with the promise of combination regimens and increased focus non\u2010invasive endpoints suggests that the future looks bright for patients living with fibrotic MASH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apt.70921","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:33:14Z","timestamp":1787023994000},"page":"1184-1196","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Review Article: Fibrosis Reversal in Metabolic Dysfunction\u2010Associated Steatohepatitis\u2014The Promise of Emerging Therapeutics"],"prefix":"10.1111","volume":"64","author":[{"given":"Malek","family":"Ayoub","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology University of Chicago Pritzker School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6571-9874","authenticated-orcid":false,"given":"Tsubasa","family":"Tsutsumi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology University of Chicago Pritzker School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0620-9705","authenticated-orcid":false,"given":"Mary E.","family":"Rinella","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology University of Chicago Pritzker School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajt.2025.01.022"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2024.0431"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/LVT.0000000000000688"},{"key":"e_1_2_12_5_1","unstructured":"U.S. Food and Drug Administration \u201cFDA Approves First Treatment for Patients With Liver Scarring Due to Fatty Liver Disease \u201dMarch 14 2024 accessed June 14 2026 https:\/\/www.fda.gov\/news\u2010events\/press\u2010announcements\/fda\u2010approves\u2010first\u2010treatment\u2010patients\u2010liver\u2010scarring\u2010due\u2010fatty\u2010liver\u2010disease."},{"key":"e_1_2_12_6_1","unstructured":"U.S. Food and Drug Administration \u201cFDA Approves Treatment for Serious Liver Disease Known as \u2018MASH \u2019\u201dAugust 15 2025 accessed June 14 2026 https:\/\/www.fda.gov\/drugs\/news\u2010events\u2010human\u2010drugs\/fda\u2010approves\u2010treatment\u2010serious\u2010liver\u2010disease\u2010known\u2010mash."},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2309000"},{"key":"e_1_2_12_8_1","unstructured":"Madrigal Pharmaceuticals \u201cMadrigal Pharmaceuticals Reports Fourth\u2010Quarter and Full\u2010Year 2025 Financial Results \u201dFebruary 19 2026 accessed June 14 2026 https:\/\/ir.madrigalpharma.com\/news\u2010releases\/news\u2010release\u2010details\/madrigal\u2010pharmaceuticals\u2010reports\u2010fourth\u2010quarter\u2010and\u2010full\u2010year\u20100."},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2022.04.014"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2029349"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.70256"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-026-01187-8"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29466"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2005.10.013"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.1447"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.18501"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc22-0556"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2016.453"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000323"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2023.04.003"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.02.027"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.07.006"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0104-9"},{"issue":"1","key":"e_1_2_12_24_1","first-page":"S10","article-title":"Pathogenesis of MASLD and MASH \u2010 Role of Insulin Resistance and Lipotoxicity","volume":"59","author":"Bansal S. K.","year":"2024","journal-title":"Alimentary Pharmacology & Therapeutics"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.04.034"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31108"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2024.06.008"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2024.10.018"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.70382"},{"key":"e_1_2_12_30_1","unstructured":"ClinicalTrials.gov \u201cA Randomized Double\u2010blind Placebo\u2010Controlled Phase 3 Study to Evaluate the Effect of Resmetirom on Liver\u2010Related Outcomes in Patients With Well\u2010compensated (Child\u2010Pugh A) Non\u2010alcoholic Steatohepatitis (NASH) Cirrhosis (MAESTRO\u2010NASH OUTCOMES) \u201dNCT05500222 accessed June 14 2026 https:\/\/clinicaltrials.gov\/study\/NCT05500222."},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2026.03.011"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-03799-0"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2413258"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.18331"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2401943"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2416394"},{"key":"e_1_2_12_37_1","unstructured":"ClinicalTrials.gov \u201cA Master Protocol for a Randomized Controlled Clinical Trial of Multiple Pharmacologic Agents in Adult Participants With Metabolic Dysfunction\u2010Associated Steatotic Liver Disease Who Are at Increased Risk of Developing Major Adverse Liver Outcomes \u201dNCT07165028 accessed June 14 2026 https:\/\/clinicaltrials.gov\/study\/NCT07165028."},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.70196"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.07.033"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00413"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2023.171003"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2401755"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(25)02114-2"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2022.07.013"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03018-2"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2024.04.034"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(25)01073-6"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2304286"},{"key":"e_1_2_12_49_1","unstructured":"ClinicalTrials.gov \u201cA Study Evaluating the Efficacy and Safety of Pegozafermin in Participants With MASH and Fibrosis (ENLIGHTEN\u2010Fibrosis) \u201dNCT06318169 accessed June 14 2026 https:\/\/clinicaltrials.gov\/study\/NCT06318169."},{"key":"e_1_2_12_50_1","unstructured":"ClinicalTrials.gov \u201cA Study to Evaluate the Efficacy and Safety of Pegozafermin in Participants With Compensated Cirrhosis Due to MASH (ENLIGHTEN\u2010Cirrhosis) \u201dNCT06419374 accessed June 14 2026 https:\/\/clinicaltrials.gov\/study\/NCT06419374."},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(25)02276-7"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(24)00246-2"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000647"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31875-0"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1018"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2502242"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.70565"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(23)00068-7"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2024.05.008"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2021-324264"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2020.08.061"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2026.01.039"},{"key":"e_1_2_12_63_1","article-title":"Comparative Efficacy of Phase 2\u20103 Therapies for Non\u2010Cirrhotic Metabolic Dysfunction\u2010Associated Steatohepatitis: An Updated Network Meta\u2010Analysis","volume":"7","author":"Tsutsumi T.","year":"2026","journal-title":"Medicus"}],"container-title":["Alimentary Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apt.70921","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/apt.70921","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apt.70921","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:14:17Z","timestamp":1791558857000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apt.70921"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,17]]},"references-count":62,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,11]]}},"alternative-id":["10.1111\/apt.70921"],"URL":"https:\/\/doi.org\/10.1111\/apt.70921","archive":["Portico"],"relation":{},"ISSN":["0269-2813","1365-2036"],"issn-type":[{"value":"0269-2813","type":"print"},{"value":"1365-2036","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,17]]},"assertion":[{"value":"2026-04-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}