Risk association of hepatocellular carcinoma with S-gene additional N-glycosylation mutation of hepatitis B virus in HBsAg and anti-HBs coexistent patients / 解放军医学杂志

ABSTRACT

Objective To investigate the association of additional N-glycosylation mutation in major hydrophilic region (MHR) of hepatitis B virus (HBV) S gene with the risk of hepatocellular carcinoma (HCC) in HBsAg and anti-HBs coexistent patients. Methods A total of 284 patients with coexistence of HBsAg and anti-HBs were enrolled in this study, who were admitted in 302 Hospital of PLA from July 2009 to June 2016. HBV DNA was extracted from serum samples and subjected to nested PCR for full-length S-gene sequencing. The association of MHR additional N-glycosylation mutation and clinical parameters with HCC occurrence risk was analyzed. Specifically, the additional N-glycosylation mutation was dynamically analyzed pre-and post-HCC occurrence for 18 patients. Results Multivariate analysis showed that age >40 years, HBsAg >median, HBeAg negativity, and additional N-glycosylation mutation in MHR were associated with HCC occurrence for the HBsAg and anti-HBs coexistent patients (OR=4.281, 95%CI 1.843-9.941, P=0.001; OR=3.146, 95%CI 1.633-6.060, P=0.001; OR=2.097, 95%CI 1.010-4.357, P=0.047; and OR=4.381, 95%CI 1.842-10.417, P=0.001). In contrast, ALT, anti-HBs, anti-HBe, and HBV DNA levels had no significant association with HCC occurrence. Dynamical analysis showed that the additional N-glycosylation mutation had already developed 1-4 years prior to HCC occurrence in the 8 of 18 observed patients. Conclusion Additional N-glycosylation mutation in MHR of HBV S gene had close association with HCC occurrence in HBsAg and anti-HBs coexistent patients, suggesting that HBsAg and anti-HBs coexistence and additional N-glycosylation mutation together could serve as a predictive indicator for HCC occurrence in chronic HBV-infected patients.