Inequalities in Developing Cirrhosis Complications Over Time: A Cohort Study

INTRODUCTION: – Current knowledge of cirrhosis progression is derived from outdated data.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 January 10, 2010, to August 30, 2015, with follow-up through August 31, 2023. A semi-Markov multistate model with 7 states and 15 transitions was used to evaluate the progression from compensated cirrhosis to ascites, hepatic encephalopathy, variceal bleeding, hepatocellular carcinoma, multiple complications, or death, considering age and etiology (cured/active hepatitis C virus, alcohol, metabolic dysfunction-associated steatotic liver disease) 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, whereas 26% remained compensated. The 2-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, whereas older patients and those with active hepatitis C virus had a higher incidence of hepatocellular carcinoma. Transition rates were similar for patients with alcohol and metabolic dysfunction-associated steatotic liver disease. DISCUSSION: – In a contemporary cirrhosis cohort, half of patients progressed, whereas 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.