{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:22:06Z","timestamp":1791422526525,"version":"4.3.3"},"reference-count":104,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Institute","award":["RO3CA249487"],"award-info":[{"award-number":["RO3CA249487"]}]},{"DOI":"10.13039\/100000738","name":"Veterans Affairs","doi-asserted-by":"publisher","award":["2I01BX000824"],"award-info":[{"award-number":["2I01BX000824"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic-associated fatty liver disease (MAFLD), is the most prevalent liver disease worldwide. It is associated with an increased risk of developing hepatocellular carcinoma (HCC) in the background of cirrhosis or without cirrhosis. The prevalence of NAFLD-related HCC is increasing all over the globe, and HCC surveillance in NAFLD cases is not that common. In the present review, we attempt to summarize promising treatments and clinical trials focused on NAFLD, nonalcoholic steatohepatitis (NASH), and HCC in the past five to seven years. We categorized the trials based on the type of intervention. Most of the trials are still running, with only a few completed and with conclusive results. In clinical trial NCT03942822, 25 mg\/day of milled chia seeds improved NAFLD condition. Completed trial NCT03524365 concluded that Rouxen-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) results in histological resolution of NASH without worsening of fibrosis, while NCT04677101 validated sensitivity\/accuracy of blood biomarkers in predicting NASH and fibrosis stage. Moreover, trials with empagliflozin (NCT05694923), curcuvail (NCT06256926), and obeticholic acid (NCT03439254) were completed but did not provide conclusive results. However, trial NCT03900429 reported effective improvement in fibrosis by at least one stage, without worsening of NAFLD activity score (NAS), as well as improvement in lipid profile of the NASH patients by 80 or 100 mg MGL-3196 (resmetirom). Funded by Madrigal Pharmaceuticals, Rezdiffra (resmetirom), used in the clinical trial NCT03900429, is the first FDA-approved drug for the treatment of NAFLD\/NASH.<\/jats:p>","DOI":"10.3390\/ijms26010306","type":"journal-article","created":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T11:24:19Z","timestamp":1735730659000},"page":"306","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["NAFLD and NAFLD Related HCC: Emerging Treatments and Clinical Trials"],"prefix":"10.3390","volume":"26","author":[{"given":"Tripti","family":"Khare","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, University of Missouri, Columbia, MO 65212, USA"},{"name":"Harry S Truman Memorial Veterans\u2019 Hospital, Columbia, MO 65201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5925-8259","authenticated-orcid":false,"given":"Karina","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8001-7087","authenticated-orcid":false,"given":"Lindiwe Oslee","family":"Chilambe","sequence":"additional","affiliation":[{"name":"School of Medicine, Copperbelt University, Kitwe P.O. Box 21692, Zambia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharad","family":"Khare","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, University of Missouri, Columbia, MO 65212, USA"},{"name":"Harry S Truman Memorial Veterans\u2019 Hospital, Columbia, MO 65201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S0140-6736(21)01701-3","article-title":"The EASL-Lancet Liver Commission: Protecting the next generation of Europeans against liver disease complications and premature mortality","volume":"399","author":"Karlsen","year":"2022","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/s41575-020-00381-6","article-title":"Global epidemiology of NAFLD-related HCC: Trends, predictions, risk factors and prevention","volume":"18","author":"Huang","year":"2021","journal-title":"Nat. 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