{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:20:25Z","timestamp":1790533225927,"version":"4.1.0"},"reference-count":203,"publisher":"Georg Thieme Verlag KG","issue":"03","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Liver Dis"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:p>Nonalcoholic steatohepatitis (NASH) is a burgeoning global health crisis that mirrors the obesity pandemic. This global health crisis has stimulated active research to develop novel NASH pharmacotherapies targeting dysregulated inflammatory, cellular stress, and fibrogenetic processes that include (1) metabolic pathways to improve insulin sensitivity, de novo lipogenesis, and mitochondrial utilization of fatty acids; (2) cellular injury or inflammatory targets that reduce inflammatory cell recruitment and signaling; (3) liver\u2013gut axis targets that influence bile acid enterohepatic circulation and signaling; and (4) antifibrotic targets. In this review, we summarize several of the therapeutic agents that have been studied in phase 2 and 3 randomized trials. In addition to reviewing novel therapeutic drugs targeting nuclear receptor pathways, liver chemokine receptors, liver lipid metabolism, lipotoxicity or cell death, and glucagon-like peptide-1 receptors, we also discuss the rationale behind the use of combination therapy and the lessons learned from unsuccessful or negative clinical trials.<\/jats:p>","DOI":"10.1055\/a-1877-9656","type":"journal-article","created":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T18:40:26Z","timestamp":1655404826000},"page":"379-400","source":"Crossref","is-referenced-by-count":38,"title":["Nonalcoholic Steatohepatitis Drug Development Pipeline: An Update"],"prefix":"10.1055","volume":"42","author":[{"given":"Nicholas W. S.","family":"Chew","sequence":"additional","affiliation":[{"name":"Department of Cardiology, National University Heart Centre, National University Hospital, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng Han","family":"Ng","sequence":"additional","affiliation":[{"name":"Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Truong","sequence":"additional","affiliation":[{"name":"Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mazen","family":"Noureddin","sequence":"additional","affiliation":[{"name":"Division of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Fatty Liver Program, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kris V.","family":"Kowdley","sequence":"additional","affiliation":[{"name":"Liver Institute Northwest and Elson S. 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