Long-Term Liver Outcomes in Wilson’s Disease: Predictors of Survival and Hepatocellular Carcinoma

Background/Aims: Wilson's disease (WD) is an inherited and treatable disorder of copper metabolism with hepatic or neurological manifestations. It continues to pose challenges in clinical management, and long-term outcome data remain limited. This study investigated hepatic involvement and clinical outcomes in cohorts from Taiwan. Methods: Longitudinal data from 146 patients with WD, retrieved from the medical database of a tertiary referral center, were analyzed (mean age at diagnosis 20.7 ± 12.4 years; mean follow-up 16.8 ± 10.8 years; maximum 51.8 years). All patients received standard treatment and care. Results: Nine patients (6.2%) underwent liver transplantation, 6 patients (4.1%) died, and 3 patients (2.1%) developed hepatocellular carcinoma (HCC). Thrombocytopenia <100 K/μL at diagnosis was associated with reduced survival (P=0.0001). Univariate Cox regression identified thrombocytopenia at diagnosis as a strong predictor of liver transplantation or death (P = 0.0001; hazard ratio (HR): 8.41; 95% CI: 2.97-23.78). Consistently, thrombocytopenia <100 K/μL was associated with reduced survival (P < 0.0001) in an external cohort of 155 patients. In the original cohort, the estimated annual HCC risk was 0.12% (95% CI: 0.03-0.36), increasing to 0.86% (95% CI: 0.18-2.5) in those with thrombocytopenia at diagnosis (P=0.029). An exploratory Firth penalized logistic regression showed that older age at diagnosis was associated with higher odds of developing HCC (odds ratio: 1.096; 95% CI: 1.009-1.191; P = 0.031). Conclusion: WD patients have a high rate of liver fibrosis, regardless of whether they present with neurological and hepatic symptoms, and are at risk of developing HCC, warranting lifelong hepatic surveillance.