Efficacy and safety of drugs for nonalcoholic steatohepatitis

• Published in: Journal of digestive diseases 2021-02, Vol.22 (2), p.72-82
• Main Authors: Shen, Bo, Lu, Lun Gen
• Format: Article
• Language: English
• Subjects: Cirrhosis; clinical trial; Clinical trials; Diabetes mellitus (non-insulin dependent); Drugs; efficacy; Fatty liver; Fibrosis; Inflammation; Liver cirrhosis; Liver diseases; non‐alcoholic steatohepatitis; Patients; Pioglitazone; safety; Vitamin E
• ISSN: 1751-2972; 1751-2980
• DOI: 10.1111/1751-2980.12967

Nonalcoholic steatohepatitis (NASH) is an inflammatory type of nonalcoholic fatty liver disease and is associated with the development and progression of cirrhosis. Lifestyle intervention is still the predominant treatment for NASH. So far, no drugs have been approved to treat NASH by the U.S. Food and Drug Administration (FDA). Vitamin E has been recommended for patients with NASH without type 2 diabetes mellitus (T2DM), whereas a combination of pioglitazone and vitamin E is recommended for patients with both NASH and T2DM. Encouragingly, drugs are currently being developed for different NASH mechanisms. Some of the drugs are at phase III clinical trials, including obeticholic acid (OCA), Elafibranor, Cenicriviroc, Selonsertib, Resmetirom, Emricasan and Aramchol. Due to its positive interim effect in attenuating the degree of hepatic fibrosis OCA was filing in FDA. However, it has been rejected by the U.S FDA and has been advised to conduct long‐term studies. Therefore, in this article, we reviewed the efficacy and safety of drugs currently under clinical trials for NASH. Nonalcoholic steatohepatitis (NASH) drugs mainly aim at patients’ weight loss, and at the antioxidant, glucose and lipid metabolism, the bile acid metabolism, liver inflammation and apoptosis. Resmetirom (MGL‐3196), Aramchol, glucagon‐like peptide‐1 (GLP‐1) agonists and peroxisome proliferator‐activated receptor (PPAR) agonists mainly target the glucose and lipid metabolism; NMG28 and farnesoid X receptor (FXR) agonists target the bile acid metabolism; CCR2/5 inhibitors, Emricasan and Selonsertib, mainly aim at inflammation and apoptosis. Due to their positive interim effect in attenuating the degree of liver fibrosis, the long‐term clinical effects of FXR agonist and CCR2/5 inhibitors deserve our full attention.