Real-World Clinical Outcomes Associated with Progression and Cirrhosis in Metabolic Dysfunction-Associated Steatohepatitis

Abstract

Background: While the clinical burden of liver disease progression among individuals with metabolic dysfunction-associated steatohepatitis (MASH) is substantial, real-world data quantifying how cirrhosis contributes to that burden are lacking. Aim: To assess the risk of progression and death among patients with MASH without baseline cirrhosis; and risk of subsequent advanced liver events and death among patients with MASH and baseline cirrhosis. Methods: The Optum de-identified Clinformatics® Data Mart Database (CDM) (Oct 1, 2015-Dec 31, 2022) was used to identify adults with MASH. Patients were grouped according presence of baseline cirrhosis. Risk of and time to progression or subsequent advanced liver events, composite clinical outcome, and all-cause death were estimated using Cox proportional hazards models. Results: Among patients without baseline cirrhosis (n=19,419), 21.8% progressed over follow-up, and the risk of progression was 28% higher for those with comorbid cardiovascular disease (CVD; hazard ratio[95% confidence interval]=1.28[1.19-1.38]) or type 2 diabetes mellitus (T2DM; 1.28[1.20-1.37]) at baseline. Risk of experiencing a composite clinical outcome during the follow-up also increased with age, and comorbid CVD or T2DM, for both cohorts without and with cirrhosis (n=9,157). Risk of death was significantly higher for patients with baseline cirrhosis (4.68[4.29-5.12]), males (1.20[1.12-1.29]), those with CVD (1.58[1.40-1.78]), and those with T2DM (1.78[1.65-1.92]). Conclusions: Clinical burden associated with MASH is high and substantially greater for patients with cirrhosis. Risks of progression and death increased with age and metabolic conditions. Therapies slowing cirrhosis development may reduce the risk of progression to advanced liver disease and death, for those suffering from MASH.