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 sero-positive 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 to subjects with HBV DNA<2,000IU/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 2,000-19,999 IU/ml to≥20,000 IU/ml. Compared to 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 IU/ml to ≥1,000 IU/ml. Compared to subjects with HBV DNA<2,000 IU/ml and HBsAg<100IU/ml, the adjusted ORs were increased from 2.20 (95%CI: 1.07-4.49) for those with HBV DNA<2,000IU/ml and HBsAg≥100IU/ml to 6.94 (95%CI: 3.39-14.23) for those with HBVDNA≥2,000IU/ml and HBsAg<1,000IU/ml, and 16.15 (95%CI: 7.60-34.32) for those with HBVDNA≥2,000IU/ml and HBsAg≥1,000IU/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 <2,000 IU/ml and HBsAg level to <100 IU/ml to lower their liver cancer risk.