Abstract
BACKGROUND AND AIMS: Chronic hepatitis B virus (HBV) infection accounts for substantial disease burden and mortality due to liver complications. Hepatitis B surface antigen (HBsAg) loss is a key component of functional cure when assessing treatment efficacy. However, the impact of HBsAg loss on clinical outcomes deserves further exploration. METHODS: This population-based cohort study used electronic health record data from a territory-wide database in Hong Kong to identify patients with chronic HBV infection (2005-2019). The association between HBsAg loss and outcomes was assessed: compensated cirrhosis, decompensated liver disease (DLD), hepatocellular carcinoma (HCC), and all-cause mortality (ACM). A marginal structural model using inverse probability weighting was used to estimate hazard ratios (HRs; 95% confidence interval [CI]) adjusted for time-fixed and time-varying confounders. Health-care resource utilization before and after loss was evaluated. RESULTS: The study population comprised 71,077 patients accruing 348,379 person-years; 1639 (2.3%) experienced HBsAg loss, which occurred with a mean (standard deviation) of 74.63 (37.5) months after chronic HBV index date. HBsAg loss was associated with a reduced risk of DLD (74%; HR 0.26 [95% CI 0.08-0.83]), HCC (66%; 0.34 [0.19-0.61]), and ACM (26%; 0.74 [0.57-0.97]). The HR for compensated cirrhosis was 0.57 (0.30-1.14). Each additional month of HBsAg loss was associated with decreased risk of HCC and ACM. Of those experiencing HBsAg loss, cumulative probability of persistence at 24 and 60 months was 99% and 97%, respectively. Hospital admission, inpatient days, and drug prescribing were higher before HBsAg loss versus 6, 12, and 24 months post-HBsAg loss. CONCLUSION: In this large population-based study with extended follow-up in Hong Kong, HBsAg loss was associated with reduced risk of DLD, HCC, and ACM.