Nonalcoholic Steatohepatitis Drug Development Pipeline: An Update

Nicholas W. S. Chew; Cheng Han Ng; Emily Truong; Mazen Noureddin; Kris V. Kowdley

doi:10.1055/a-1877-9656

Seminars in Liver Disease, Table of Contents

Semin Liver Dis 2022; 42(03): 379-400
DOI: 10.1055/a-1877-9656

Review Article

Nonalcoholic Steatohepatitis Drug Development Pipeline: An Update

Nicholas W. S. Chew

¹Department of Cardiology, National University Heart Centre, National University Hospital, Singapore, Singapore

,

Cheng Han Ng

²Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

,

Emily Truong

³Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California

,

Mazen Noureddin

⁴Division 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

⁵Liver 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 - intervention

Full Text

References

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