Emerging mechanisms of non-alcoholic steatohepatitis and novel drug therapies

Abstract

Non-alcoholic fatty liver disease (NAFLD) has become a leading cause of chronic liver disease globally. It initiates with simple steatosis (NAFL) and can progress to the more severe condition of non-alcoholic steatohepatitis (NASH). NASH often advances to end-stage liver diseases such as liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Notably, the transition from NASH to end-stage liver diseases is irreversible, and the precise mechanisms driving this progression are not yet fully understood. Consequently, there is a critical need for the development of effective therapies to arrest or reverse this progression. This review provides a comprehensive overview of the pathogenesis of NASH, examines the current therapeutic targets and pharmacological treatments, and offers insights for future drug discovery and development strategies for NASH therapy.

Keywords

Metabolic dysfunction / Drug development / Bile acids / Liver-gut axis / Inflammation / Fibrosis

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Funding

National Natural Science Foundation of China(82070883)

National Natural Science Foundation of China(82273982)

Natural Science Foundation of Jiangsu Province(BK20221525)

Scientific Research Foundation for High-level Faculty, China Pharmaceutical University.