A multicenter multistate modeling on the natural history of liver decompensation: Longitudinal analysis of 1777 patients.
Abstract
BACKGROUND: Cirrhosis often remains silent until decompensation, after which survival deteriorates sharply. Contemporary, transition-aware estimates are limited, especially in Asian-predominant cohorts. We analyzed trajectories from compensated advanced chronic liver disease (cACLD) through sequential decompensations to death. METHOD: In this multicenter study, we analyzed retrospective data from an adult cohort with liver stiffness ≥15 kPa from vibration-controlled transient elastography across 19 institutions internationally. Decompensation included ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, or variceal bleeding. Multistate models were constructed to characterize patient trajectories across 4 main clinically meaningful states: baseline cACLD, first decompensation, a subsequent second decompensation, and death. Etiology-specific subgroup analyses were conducted, and the effects of univariable predictors on transitions were also examined. RESULTS: Among 1777 patients, 265 (14.9%) developed a first decompensation over a median follow-up of 4.25 years. In the main multistate analysis cohort, from baseline cACLD, first decompensation occurred in 215 patients at 3.10 per 100 person-years, while death occurred at a rate of 1.01 per 100 person-years. The rate of a second decompensation was higher following the first decompensation, at 42.73 per 100 person-years. Patients with alcohol-associated liver disease had the highest rate of progression from baseline to first decompensation, whereas patients with hepatitis B etiology had the lowest progression rate into a second decompensation following a first decompensating event. CONCLUSION: Most patients with cACLD remain compensated over 10 years of follow-up, but once decompensation occurs, trajectories accelerate, and survival worsens. Transition-aware, etiology-stratified estimates enable individualized prognostication and earlier risk-guided intervention, including timely transplant referral.
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Authors: Eunice X X Tan, Nicole Shu Ying Tang, Nicholas Syn, Daniel Q Huang, Anand V Kulkarni, Ming-Hua Zheng, Vincent L Chen, Chitchai Rattananukrom, Jimmy Che‐To Lai, Karn Wijarnpreecha, Rahul Kumar, Apichat Kaewdech, Masayuki Ueno, Akash Roy, Ken Liu, Toru Nakamura, Yanhang Gao, Masato Yoneda, Yuya Seko, Takefumi Kimura, Mazen Nourredin, Mohammad Shadab Siddiqui, Hirokazu Takahashi, Cheng Han Ng, Mark Muthiah
Institutions: The University of Sydney, Kyoto University, University of Virginia, University of Michigan, Khon Kaen University, Prince of Songkla University, National University of Singapore, National University Health System, Chinese University of Hong Kong, Yokohama City University, Changi General Hospital, Methodist Hospital, Jilin University, Kyoto Prefectural University of Medicine, Michigan Medicine, Saga University, Shinshu University, First Affiliated Hospital of Wenzhou Medical University, Shinshu University Hospital, Mayo Clinic in Florida, Royal Prince Alfred Hospital, Kurume University, National University Hospital, First Hospital of Jilin University, Kurashiki Central Hospital, University of Arizona College of Medicine- Phoenix, Asian Institute of Gastroenterology, Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Banner - University Medical Center Phoenix, Houston Institute for Clinical Research