Systematic review and meta-analysis: Development of hepatocellular carcinoma in chronic hepatitis B patients with hepatitis e antigen seroconversion

Hepatitis B e antigen (HBeAg) seroconversion is considered to have significantly favourable clinical outcomes for patients with chronic hepatitis B (CHB). However, inconsistent study results suggest that hepatocellular carcinoma (HCC) still occurs in patients with HBeAg seroconversion. We performed a systematic review and meta-analysis to determine the incidence of HCC in patients with CHB after HBeAg seroconversion. Web of Science, PubMed and Embase databases were searched through January 2017. The incidence of HCC in CHB patients after HBeAg seroconversion was pooled using a random-effects model or fix-effects model. Sixteen studies were finally included, involving 4910 patients with HBeAg seroconversion. The overall pooled proportion suggested that 3.33% (95% confidence interval (CI): 2.28%-4.58%) of patients with CHB develop HCC despite HBeAg seroconversion. In patients with HBeAg seroconversion without cirrhosis, the pooled proportion of HCC development was 0.94% (95% CI: 0.15%-2.4%). Moreover, patients with cirrhosis, active hepatitis, or aged greater than 40 years at the time of HBeAg seroconversion were at significantly higher risk for HCC development. HBeAg seroconversion was significantly associated with a reduced risk of HCC compared with persistently positive HBeAg (RR = 0.58, 95% CI: 0.35-0.97, P = .04). Despite the reduced risk with HBeAg seroconversion, HCC can still occur in a proportion of patients with CHB after HBeAg seroconversion. Long-term monitoring is needed for patients with established cirrhosis, active hepatitis or those older than 40 years at the time of HBeAg seroconversion.