Lifetime Risk of Liver Disease in Patients With β‐Thalassemia: Data From the de‐LIGHT Retrospective Cohort Study

BACKGROUND: Liver disease is common in patients with β-thalassemia, but data on lifetime incidence and risk factors are limited. METHODS: We conducted a retrospective cohort study of 557 patients with β-thalassemia followed from diagnosis for a median of 38 years. Predictive, survival, and regression analyses were used to determine the association between liver disease and potential risk factors. RESULTS: The crude incidence of liver disease was 26.4% (fibrosis/cirrhosis 24.2%, median age 34.4 years; hepatocellular carcinoma 2.3%, median age 45.4 years, 38.5% not preceded by cirrhosis). Among evaluated risk factors, only hepatitis C virus (HCV) infection (adjusted hazard ratio [HR]: 2.195, p < 0.001) and lifetime serum ferritin level (adjusted HR per 100-ng/mL increase: 1.030, p < 0.001) were significantly associated with liver disease, with a lifetime serum ferritin level > 1500 ng/mL being the best predictor (p = 0.001). Liver disease-free survival was significantly shorter in patients who had both versus either or neither risk factor (p < 0.001). Mostly severe and persistent but not mild-moderate or temporary/fluctuating elevation in liver enzymes was associated with liver disease development. CONCLUSION: Patients with β-thalassemia have a considerably increased lifetime risk of liver disease that is primarily driven by HCV infection and/or uncontrolled iron overload, especially in the 4th-5th decades of life.