Antibody to
hepatitis B surface antigen (
HBsAg) (anti-HBs) can exist in patients with
chronic hepatitis B virus (HBV)
infection. To date, little is known about the association of concurrent
HBsAg and anti-HBs (concurrent
HBsAg/ anti-HBs) with
hepatocellular carcinoma (HCC). The aim of this study was to investigate the clinical relevance of concurrent
HBsAg/anti-HBs with preS deletion mutations and HCC in chronic HBV
infection. A total of 755 patients with chronic HBV
infection were included consecutively at a tertiary center. Logistic regression analysis was used to identify risk factors for HCC, and serum HBV
DNA was amplified, followed by direct sequencing to detect preS deletions. The prevalence of concurrent
HBsAg/anti-HBs was 6.4% (48/755) and all HBVs tested were genotype C. HCC occurred more frequently in the concurrent
HBsAg/anti-HBs group than in the
HBsAg only group [22.9% (11/48) vs. 7.9% (56/707), P = 0.002]. In multivariate analyses, age >40 years [odds ratio (OR), 14.712; 95% confidence interval (CI), 4.365-49.579; P < 0.001], male gender (OR 2.431; 95% CI, 1.226-4.820; P = 0.011), decompensated
cirrhosis (OR, 3.642; 95% CI, 1.788-7.421; P < 0.001) and concurrent
HBsAg/anti-HBs (OR, 4.336; 95% CI, 1.956-9.613; P < 0.001) were associated independently with HCC. In molecular analysis, preS deletion mutations were more frequent in the concurrent
HBsAg/anti-HBs and HCC groups than in the
HBsAg without HCC group (42.3% and 32.5% vs. 11.3%; P = 0.002 and 0.012, respectively). In conclusion, concurrent
HBsAg/anti-HBs is associated with preS deletion mutations and may be one of the risk factors for HCC in chronic HBV
infection with genotype C.