Review Article

Updates on novel pharmacotherapeutics for the treatment of nonalcoholic steatohepatitis

Yong-yu Yang1, Li Xie1, Ning-ping Zhang2,3, Da Zhou2,3, Tao-tao Liu2,3,4, Jian Wu1,2,3
1 Department of Medical Microbiology & Parasitology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai 200032, China
2 Department of Gastroenterology & Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200032, China
3 Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, Shanghai 200032, China
4 Shanghai Baoshan District Wusong Central Hospital (Zhongshan Hospital Wusong Branch, Fudan University), Shanghai 200940, China
Correspondence to: Tao-tao Liu:, Jian Wu:,
DOI: 10.1038/s41401-022-00860-3
Received: 2 October 2021
Accepted: 3 January 2022
Advance online: 2 February 2022


Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD), characterized with hepatocellular steatosis, ballooning, lobular inflammation, fibrotic progression, and insulin resistance. NASH may progress
to cirrhosis and hepatocellular carcinoma (HCC), which are the major indications for liver transplantation and the causes for mortality. Thus far, there are no approved pharmacotherapeutics for the treatment of NASH. Given the complexity of NASH pathogenesis at multifaceted aspects, such as lipotoxicity, inflammation, insulin resistance, mitochondrial dysfunction and fibrotic progression, pharmacotherapeutics under investigation target different key pathogenic pathways to gain either the resolution of steatohepatitis or regression of fibrosis, ideally both. Varieties of pharmacologic candidates have been tested in clinical trials and have generated some positive results. On the other hand, recent failure or termination of a few phase II
and III trials is disappointing in this field. In face to growing challenges in pharmaceutical development, this review intends to summarize the latest data of new medications which have completed phase II or III trials, and discuss the rationale and preliminary results of several combinatory options. It is anticipated that with improved understanding of NASH pathogenesis and critical endpoints, efficient pharmacotherapeutics will be available for the treatment of NASH with an acceptable safety profile.
Keywords: nonalcoholic steatohepatitis; pharmacotherapeutics; clinical trials; NASH resolution; fibrosis regression

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