Risk Stratification of Hepatocellular Carcinoma in Hepatitis B Virus e Antigen-Negative Carriers by Combining Viral Biomarkers

Background. The serum hepatitis B virus (HBV) surface antigen (HBsAg) level can predict hepatocellular carcinoma (HCC) development in hepatitis B e antigen (HBeAg)-negative patients with an HBV DNA level of <2000 IU/mL. However, little is known regarding how well the combination of both viral biomarkers stratifies HCC risk. Methods. A total of 2165 Taiwanese HBeAg-negative noncirrhotic patients were followed for 14.9 years. The predictive power of the HBsAg level for HCC was analyzed for different viral load ranges. Results. In patients with HBV DNA levels of 2000-19 999 IU/mL (intermediate viral load), a positive correlation between HBsAg level and HCC development was identified after adjustment for other risk factors (P=.002). In contrast, no association was found between HBsAg level and HCC in patients with higher viral loads. HBsAg level was subsequently included to stratify HCC risk in patients with low and intermediate viral loads. Receiver operating characteristic curve analysis showed that combining HBV DNA and HBsAg level better predicts 10-year HCC development as compared to using HBV DNA level alone in the overall cohort (P=.028). Conclusions. Serum HBsAg level helps stratify HCC risk in patients with intermediate viral loads. Combining HBV DNA and HBsAg levels better predicts HCC risk.