Advances in Novel Drug Therapy for Metabolic Dysfunction-associated Steatohepatitis Cirrhosis

Metabolic dysfunction-associated steatotic liver disease has emerged as a leading cause of chronic liver disease and cirrhosis in the Western world. With rising rates of obesity, the prevalence of metabolic dysfunction-associated steatohepatitis (MASH)-related cirrhosis is expected to increase. MASH is associated with chronic hepatic inflammation and progressive liver fibrosis, and significant research is focused on developing pharmacological therapies to reverse these downstream complications. Recent trials have explored various therapeutic targets across metabolic, inflammatory, and fibrogenic pathways aimed at decreasing liver triglycerides, inflammation, lipotoxicity, and fibrosis. Some of these drugs show promise in reversing biomarkers and/or histologic markers of steatohepatitis and fibrosis, although most have been primarily studied in non-cirrhotic patients. However, in the context of the significant unmet medical need of patients with MASH-associated cirrhosis, growing interest in targeting compensated cirrhosis has prompted renewed investment in numerous early clinical and late-stage programs evaluating novel investigational agents in this population. This review summarizes current therapies under evaluation in phase 2 and 3 clinical trials for MASH-related cirrhosis, highlighting drug mechanisms, outcomes, and future research directions.