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Review
. 2022 May;43(5):1191-1199.
doi: 10.1038/s41401-021-00822-1. Epub 2021 Dec 14.

Current status and challenges in the drug treatment for fibrotic nonalcoholic steatohepatitis

Yi-Wen Shi  1 , Jian-Gao Fan  2
Affiliations
Review

Current status and challenges in the drug treatment for fibrotic nonalcoholic steatohepatitis

Yi-Wen Shi et al. Acta Pharmacol Sin. 2022 May.

Abstract

Currently, nonalcoholic steatohepatitis (NASH) is one of the most common forms of chronic hepatitis, increasing the burden of health care worldwide. In patients with NASH, the fibrosis stage is the most predictive factor of long-term events. However, there are still no drugs approved by the Food and Drug Administration of the United States for treating biopsy-proven NASH with fibrosis or cirrhosis. Although some novel drugs have shown promise in preclinical studies and led to improvement in terms of hepatic fat content and steatohepatitis, a considerable proportion of them have failed to achieve histological endpoints of fibrosis improvement. Due to the large number of NASH patients and adverse clinical outcomes, the search for novel drugs is necessary. In this review, we discuss current definitions for the evaluation of treatment efficacy in fibrosis improvement for NASH patients, and we summarize novel agents in the pipeline from different mechanisms and phases of trial. We also critically review the challenges we face in the development of novel agents for fibrotic NASH and NASH cirrhosis.

Keywords: cirrhosis; liver fibrosis; nonalcoholic steatohepatitis; novel therapies; treatment efficacy.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Summary of treatment efficacy of drugs with histological endpoint of fibrosis improvement ≥1 stage without worsening of NASH.
OCA obeticholic acid.
Fig. 2
Fig. 2. Summary of treatment efficacy of drugs with histological endpoint of NASH resolution without worsening of fibrosis.
OCA obeticholic acid.
Fig. 3
Fig. 3. The challenges in the research and development of novel drugs for fibrotic NASH.
R&D research and development, LBx liver biopsy, NASH nonalcoholic steatohepatitis.
See this image and copyright information in PMC

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