Contemporary clinical course of compensated advanced chronic liver disease in a multistate framework

Abstract Background Compensated advanced chronic liver disease (cACLD) encompasses patients with advanced fibrosis/cirrhosis at risk for liver-related complications. The natural history of cACLD has been extrapolated from compensated cirrhosis and historic cohorts, although major advances in diagnosis and management have impacted the clinical course and understanding of disease trajectories. Methods From 2015 to 2022, 1140 consecutive patients with cACLD (first-time liver stiffness measurement [LSM] ≥10 kPa) at the Vienna General Hospital were followed for first and further decompensation, and death. Baseline data (age, sex, etiological cure, LSM, MELD, platelet count, and albumin) were incorporated into a multistate modelling framework to investigate transition-specific associations. Results 42% had steatotic liver disease and 37% viral hepatitis. Median LSM at baseline was 16 kPa, and 93% had Child–Turcotte–Pugh stage A. Median follow-up was 3.9 years. Two and 5-year probabilities were: 89%/74% to remain compensated, 3.7%/3.6% for first decompensation, 0.6%/2.1% for further decompensation, 3.7%/12% for liver-related and 2.8%/7.9% for non-liver-related death. LSM ≥15 kPa and ANTICIPATE±NASH ≥75% identified subgroups at particular risk for hepatic decompensation (5.7% vs. 1.5%/ 9.1% vs. 2.1% at 2 years) and liver-related death, but not for non-liver-related death, which was as frequent as hepatic decompensation in those with LSM <15 kPa. LSM and markers of liver dysfunction predicted hepatic decompensation, whereas etiological cure and platelet count were associated with further decompensation. Conclusion The risk of hepatic decompensation in contemporary patients with cACLD is lower than in previous reports on compensated cirrhosis. Hepatic decompensation accelerates disease progression.