Individual and combined effects of hepatitis B surface antigen level and viral load on liver cancer risk.

Background: Hepatitis B surface antigen (HBsAg) and viral load are both hallmarks of hepatitis B virus (HBV) infection and have potential to stratify liver cancer risk.

Methods: We carried out a nested case-control study including 211 liver cancer cases and 221 controls who were seropositive for HBsAg within two population-based cohorts in Shanghai. Logistic regression was performed to estimate the odds ratios (ORs) and 95% confidence intervals (CIs).

Results: Risk of liver cancer was positively related to increasing levels of HBV-DNA and HBsAg in dose-response manners. Compared with subjects with HBV-DNA < 2000 IU/ml, the adjusted ORs increased from 2.11 (95%CI: 0.99-4.50) to 10.47 (95%CI: 5.06-21.68) for those with HBV-DNA level at 2000-19 999 to ≥ 20 000 IU/ml. Compared with subjects at a low level of HBsAg (0.05-99 IU/ml), the adjusted ORs increased from 1.82 (95%CI: 0.90-3.68) to 2.21 (95%CI: 1.10-4.43) for those with HBsAg level at 100-999 to ≥ 1000 IU/ml. Compared with subjects with HBV-DNA < 2000 IU/ml and HBsAg < 100 IU/ml, the adjusted ORs were increased from 2.20 (95%CI: 1.07-4.49) for those with HBV-DNA < 2000 and HBsAg ≥ 100 IU/ml to 6.94 (95%CI: 3.39-14.23) for those with HBV-DNA ≥ 2000 IU/ml and HBsAg < 1000 IU/ml, and 16.15 (95%CI: 7.60-34.32) for those with HBV-DNA ≥ 2000 IU/ml and HBsAg ≥ 1000 IU/ml.

Conclusion: Elevated levels of HBV-DNA and HBsAg are associated with increased risks of liver cancer. Chronic HBsAg carriers may be suggested to simultaneously lower the viral load to < 2000 IU/ml and HBsAg level to < 100 IU/ml to lower their liver cancer risk.