Author information

¹MASLD Research Center, Division of Gastroenterology and Hepatology, University of California, San Diego, La Jolla, CA 92103, USA.

²Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; Newcastle NIHR Biomedical Research Center, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK.

³MASLD Research Center, Division of Gastroenterology and Hepatology, University of California, San Diego, La Jolla, CA 92103, USA; School of Public Health, University of California, San Diego, La Jolla, CA 92103, USA. Electronic address: roloomba@ucsd.edu.

Abstract

Metabolic dysfunction-associated steatohepatitis (MASH) is a leading etiology of chronic liver disease worldwide, with increasing incidence and prevalence in the setting of the obesity epidemic. MASH is also a leading indication for liver transplantation, given its associated risk of progression to end-stage liver disease. A key challenge in managing MASH is the lack of approved pharmacotherapy. In its absence, lifestyle interventions with a focus on healthy nutrition and regular physical activity have been the cornerstone of therapy. Real-world efficacy and sustainability of lifestyle interventions are low, however. Pharmacotherapy development for MASH is emerging with promising data from several agents with different mechanisms of action (MOAs) in phase 3 clinical trials. In this review, we highlight ongoing challenges and potential solutions in drug development for MASH and provide an overview of available data from emerging therapies across multiple MOAs.