Large population study on the natural history of spontaneous hepatitis b e-antigen seroconversion: risk of hepatocellular carcinoma

Abstract

Background and Aims: In patients with chronic hepatitis B (CHB), HBeAg positivity is associated with increased risk of hepatocellular carcinoma (HCC) during long-term follow-up. However at the time of HCC development, over 70% of patients already has e-seroconversion. The aim of this study is to identify factors associated with development of HCC in patients after spontaneous e-seroconversion in a large population. Methods: All patients seen at the Hepatitis Clinic, Queen Mary Hospital, Hong Kong, with documented spontaneous e-seroconversion was identified and included. Patients were monitored 3-6 monthly for acute exacerbations and the development of HCC. Results: A total of 602 patients were included with a median follow-up of 8.8 years (range, 0.6-23.8 years), of which 349 (58%) were males. Nineteen patients developed HCC diagnosed at a median interval of 4.3 years after e-seroconversion (range, 1.4-14.4 years). Significant risk factors for HCC development by log-rank test included the age of e-seroconversion, presence of underlying cirrhosis at the time ofe-seroconversion, peak AFP levels before and after e-seroconversion, and post-seroconversion median ALT levels. Using multivariate analysis by Cox regression analysis, both cirrhosis (OR 4.128, 95% C1 1.283-13.276) and age of seroconversion (OR 1.099, 95% CI 1.055-1.146) remained significant factors associated with risk of HCC, (p=0.017 and p iO.OO1 respectively). In patients aged between 40 and 65 years with HCC, the time of e-seroconversion was compared to age-matched controls at a ratio of 1.4. There was a significantly higher median age of e-seroconversion in HCC patients compared with controls (46 vs 42 years respectively, p = 0.049). The cumulative HCC incidence at 5 and 10 years from the time of e-seroconversion for different age groups is shown below. The 15-year cumulative incidence of HCC in patients with cirrhosis after spontaneous HBeAg seroconversion was 32% compared with 2% in patients without cirrhosis (p 0.001). Conclusion: In patients undergoing spontaneous HBeAg seroconversion, older age of seroconversion and underlying cirrhosis were significant factors associated with increase nsk of HCC development.