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Semin Liver Dis 2022; 42(03): 379-400
DOI: 10.1055/a-1877-9656
DOI: 10.1055/a-1877-9656
Review Article
Nonalcoholic Steatohepatitis Drug Development Pipeline: An Update
Nicholas W. S. Chew
1
Department of Cardiology, National University Heart Centre, National University Hospital, Singapore, Singapore
,
Cheng Han Ng
2
Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
,
Emily Truong
3
Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California
,
Mazen Noureddin
4
Division of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Fatty Liver Program, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California
,
Kris V. Kowdley
5
Liver Institute Northwest and Elson S. Floyd College of Medicine, Washington State University, Seattle, Washington
› Author Affiliations
Abstract
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–gut 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.
Keywords
pharmacology - nonalcoholic fatty liver disease - nonalcoholic steatohepatitis - interventionPublication History
Accepted Manuscript online:
16 June 2022
Article published online:
24 August 2022
© 2022. Thieme. All rights reserved.
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