Pharmacotherapies for Liver Fibrosis, NASH Resolution Ranked

Although NASH is a common cause of chronic liver disease, there is limited evidence surrounding its management.

Pharmacotherapies used in the treatment of nonalcoholic steatohepatitis (NASH) were compared in a recent systematic review and network meta-analysis published in Alimentary Pharmacology & Therapeutics.

Although NASH is a common cause of chronic liver disease, there is limited evidence surrounding its management. To determine the relative “rank-order” of available therapeutic interventions used to improve liver fibrosis as well as provide NASH resolution, the authors searched several databases for randomized controlled trials (RCTs) evaluating therapies used to treat biopsy-proven NASH. The primary endpoint of interest was fibrosis improvement of 1 stage or greater; NASH resolution was established as a secondary outcome.

“We calculated the relative ranking of the interventions for achieving the primary and the secondary outcome as their surface under the cumulative ranking (SUCRA),” the authors explained. The range of SUCRA values is 0 (worst) to 1 (best), with higher scores signifying an increased probability of obtaining 1 stage or greater fibrosis improvement and/or NASH resolution.

The analysis included a total of 26 RCTs analyzing 23 interventions. Based on SUCRA score, findings revealed the 2 interventions with the highest probability of being ranked most effective in achieving fibrosis improvement (1 stage or more) were lanifibranor and obeticholic acid, with SUCRA values of 0.78 and 0.77, respectively. When compared with placebo, lanifibranor, obeticholic acid, pioglitazone and vitamin E were all found to be superior in achieving fibrosis improvement (1 stage or more).

As for NASH resolution, results showed semaglutide, liraglutide, and vitamin E plus pioglitazone had the highest probability of being ranked as most effective, with SUCRA values of 0.89, 0.84, and 0.83, respectively. When compared with placebo, semaglutide, liraglutide, vitamin E plus pioglitazone, pioglitazone alone, lanifibranor and obeticholic acid were found to be significantly better for NASH resolution.

“Larger comparative RCTs are warranted to further establish the comparative efficacy of different interventions for NASH in demonstrating 1 stage or more improvement in fibrosis and/or NASH resolution,” the authors concluded. “Therapies that have been shown to improve NASH resolution may be combined with therapies that have an antifibrotic effect to further boost treatment response rate in future.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.  

Reference

Majzoub AM, Nayfeh T, Barnard A, et al. Systematic review and network meta-analysis: comparative efficacy of pharmacologic therapies for fibrosis improvement and resolution of NASH. Aliment Pharmacol Ther. Published online August 2021. doi: 10.1111/apt.16583