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Cholankeril G, Taylor T, Kramer JR, Liu Y, Hernaez R, Patidar KR, Flores A, Lee TH, Rana A, Samuel R, Asch S, Kanwal F. Inequalities in developing cirrhosis complications over time: A cohort study. The American journal of gastroenterology. 2025 Feb 5.
INTRODUCTION: Current knowledge of cirrhosis progression is derived from outdated data. We examined the progression patterns of cirrhosis in a contemporary cohort. METHODS: We conducted a retrospective cohort study of adult patients diagnosed with compensated cirrhosis at 130 Veterans Affairs healthcare facilities from 10/1/2010 to 08/30/2015, with follow-up through 08/31/2023. A semi-Markov multistate model with 7 states and 15 transitions was used to evaluate progression from compensated cirrhosis to ascites, hepatic encephalopathy, variceal bleeding, hepatocellular carcinoma (HCC), multiple complications, or death, considering age and etiology (cured/active HCV, alcohol, metabolic dysfunction-associated steatotic liver disease [MASLD]) as time-varying factors. Results: We identified 24,679 patients with compensated cirrhosis. Over a median follow-up of 5.3 years, 49.8% progressed to a single complication, with ascites (30.3%) being the most common, and 3.1% progressed to multiple complications. A total of 12.9% transitioned directly to death from non-liver-related causes, while 26% remained compensated. The two-year risk of transitioning to death was 13.5%, exceeding the risk of any complication state. Younger patients and those with alcohol-related cirrhosis had faster progression, while older patients and those with active HCV had a higher incidence of HCC. Transition rates were similar for patients with alcohol and MASLD. DISCUSSION: In a contemporary cirrhosis cohort, half of patients progressed, while others remain compensated, and a large fraction transitioned directly to death, with age and etiology significantly influencing outcomes. These data highlight the importance of interventions in the high-yield period before the first complication.