Lifetime risk of liver-related outcomes and determinants in male inactive carriers of chronic hepatitis B

The full spectrum of risks for the life course of inactive hepatitis B virus (HBV) carriers remains unclear. In this study, 995 untreated HBV carriers (median age: 42.8 years; median follow-up: 30.2 years) were included. Their data were sourced from a population-based cohort study of male civil servants recruited in 1989–1992. Outcomes were identified by active follow-up examinations and linkage with national health insurance research database. At baseline, 483 subjects were inactive carriers, 385 with indeterminate phase, and 127 with other phases. The joint lifetime risk for incident cirrhosis, decompensation, hepatocellular carcinoma, and liver-related deaths was lower for inactive carriers compared to subjects in other phases (p < 0.0001). There was a trend of increase in incidence among inactive carriers; the 5-, 10-, and 20-year cumulative incidences were 1.86%, 6.03%, and 10.07%, respectively. Of the inactive carriers, 37.7% cleared HBsAg and 36.6% had biochemical relapse during the study. Biochemical relapse, obesity, and advanced age were predictors for disease progression in inactive carriers. Virological relapse was the predominant cause of biochemical relapse. Higher HBV-DNA levels (≥1000 copies/mL or 200 IU/mL) and HBV genotype B (vs. C) were associated with higher virological relapse rate. After 30 years, we found that one-time measure of inactive carrier state continued to have the lowest risk compared with other infection phases. Despite a more favorable prognosis, inactive carriers had a non-negligible risk. Our findings of lifetime risk may provide important clues for the management of such patients and consideration of therapeutic strategies aiming to achieve functional cure.