A Large Cohort Study Examining the Effects of Long-Term Entecavir on Hepatocellular Carcinoma and HBsAg Seroclearance

Abstract

Background: Real world studies examining reduction of risk of hepatocellular carcinoma (HCC) in patients receiving antivirals are limited either by the small-sized cohort studies, or data insufficiency and heterogeneity in electronic database with short follow-up duration. We aim to examine the long-term outcome of patients receiving entecavir treatment on HCC incidence and HBsAg seroclearance. Methods: Incidence of HCC in 1225 entecavir-treated patients between 2002 and 2015 was compared with the HCC incidence estimated using the REACH-B, GAG-HCC and CU-HCC scores. Standardized incidence ratios (SIR) were calculated. Impact of entecavir treatment on HBsAg seroclearance was explored. Results: The median follow-up of the cohort was 6.6 years, with 66 incidence cases of HCC. Using the REACH-B model, the reduction of HCC risk was significant from year 6 onwards with SIR of 0.68 (95% CI 0.535-0.866) at year 10. In subgroup patients without cirrhosis, consistent risk reduction was observed since the fifth year and SIR reached 0.51 (95% CI 0.271-0.704) by year 10. Benefit in cirrhotic patients were demonstrated when using the GAG-HCC and CU-HCC score, with SIR at year 10 being 0.38 (95% CI 0.259-0.544) and 0.46 (95% CI 0.314-0.659) respectively. The cumulative rate of HBsAg seroclearance was 5.2%. HBsAg level at third year of treatment and baseline-to-3-year percentage reduction were predictive of subsequent HBsAg seroclearance. Conclusion: Long-term entecavir therapy was associated with significant reduction in the risk of HCC in the real world. However, HBsAg seroclearance rate remained low. Additional therapy should be considered in patients with adverse predictive factor for subsequent HBsAg seroclearance.