Management of Non-alcoholic Steatohepatitis (NASH): A Systematic Review of Pharmacological Therapies

Abstract

Introduction: Non-alcoholic steatohepatitis (NASH) is the progressive form of non-alcoholic fatty liver disease (NAFLD) that can lead to cirrhosis and liver cancer. There are currently no approved pharmacological therapies. This review summarizes the evidence from late-stage clinical trials.

Methods: A systematic search was performed for phase 2b and phase 3 RCTs of pharmacological agents for biopsy-proven NASH. The primary endpoints were typically NASH resolution without worsening of fibrosis, or fibrosis improvement without worsening of NASH.

Results: The review identified trials for several drug classes, including FXR agonists (obeticholic acid), PPAR agonists (lanifibranor), and GLP-1 receptor agonists (semaglutide). Several agents met one of the primary endpoints, showing modest but significant effects on histology. However, side effects and safety concerns were noted for some agents.

Discussion: The complex pathophysiology of NASH suggests that combination therapy may be required in the future. While progress is being made, an effective and safe therapy remains elusive. Lifestyle modification remains the cornerstone of management.

Conclusion: Several emerging pharmacological therapies show modest efficacy for NASH, but a safe and highly effective agent is not yet available.