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.
Background: Racial and sex disparities have been described in liver conditions, including primary biliary cholangitis (PBC). This study sought to understand how race/ethnicity and sex-based differences impact access to diagnosis, clinical outcomes, health resource use (HRU), and treatment among patients with PBC in the United States (US). Methods: Komodo Research Database claims data (2016-2023) for adults diagnosed with PBC were analyzed retrospectively. Patients were grouped by race/ethnicity (White, Black, Hispanic, Asian, and Other) and separately by sex (male or female). Clinical characteristics, treatment patterns, and HRU outcomes were assessed pre-index and post-index. The index date was defined as the first claim with a PBC diagnosis code. Statistical significance for comparisons was defined as p<0.05. Results: In total, 9554 and 11,591 patients were included in the race/ethnicity and sex analyses. Black and Hispanic patients (versus [vs.] White) and male patients (vs. female) had higher comorbidity burden and PBC-related symptoms pre-index. Post-index, Black patients (vs. White) had significantly higher risks of liver transplant and hospitalization due to hepatic decompensation (adjusted hazard ratio [HR] of 2.09 and 1.37, respectively). Hispanic patients (vs. White) had a significantly higher risk of developing cirrhosis (adjusted HR of 1.19). Males had a higher risk than females for all adverse outcomes. Most HRU outcomes were significantly higher for Black patients vs. White, while treatment rates and response rates to ursodeoxycholic acid were significantly lower for Black patients vs. White and male patients vs. female. Conclusions: These results highlight significant differences in disease management and treatment initiation across race/ethnicity and sex groups in the US. Improved provider awareness of such differences in PBC is required to support individualized management and ensure equitable access to PBC treatment.
Objectives: To characterize longitudinal patterns of alcohol use and evaluate associations with liver enzyme changes in youth with metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: We analyzed 1172 children with biopsy-confirmed MASLD and longitudinal Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) data. Group-based trajectory modeling identified alcohol use patterns over time. Linear mixed models assessed associations between alcohol trajectory groups and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT). Generalized linear mixed models evaluated predictors of alcohol use, including age, sex, body mass index (BMI), fibrosis stage, and household income. Results: Among participants diagnosed with MASLD in childhood, 206 (17.6%) reported alcohol use during adolescence or early adulthood. Three alcohol-use groups were identified: non-users, adolescent initiators, and adult initiators. Heavy episodic drinking was reported by 48 of 71 adolescent initiators (67.6%) and 53 of 135 adult initiators (39.3%). Compared with non-users, alcohol initiators had lower liver chemistry values at enrollment but greater annual increases during follow-up. Adolescent initiators had a 4% greater annual increase in ALT, while adult initiators had 6%, 4%, and 3% greater annual increases in ALT, AST, and GGT, respectively. Conclusions: Nearly 1 in 5 youth with MASLD reported alcohol use during adolescence or early adulthood despite ongoing subspecialty care. Alcohol-use trajectories were associated with greater annual increases in liver chemistries, particularly among participants with heavy episodic drinking. These findings support routine alcohol screening and developmentally tailored anticipatory guidance in pediatric MASLD care.
