Evolution of viral biomarkers in predicting outcomes of chronic hepatitis B patients: From DNA to surface antigen

AbstractQuantification of hepatitis B virus (HBV) DNA and quantitative hepatitis B surface antigen (HBsAg) have improved our understanding and management of chronic hepatitis B (CHB). Both HBV DNA and HBsAg levels are highest in the immune tolerance phase, start to decline during the immune clearance phase, and further decline after hepatitis B e antigen (HBeAg) seroconversion. These levels are lowest in the inactive carrier state but rise again in patients who develop HBeAg-negative hepatitis. Previous studies have shown that an HBV DNA level ≥2000 IU/mL is associated with high risks of hepatocellular carcinoma, liver cirrhosis, and hepatitis activity, whereas a lower HBV DNA level is associated with a better chance of HBsAg loss, which is very close to a clinical cure for HBV infection. Recent studies further suggested that HBsAg level is not only a better predictor of HBsAg loss compared with the HBV DNA level, but also can complement the HBV DNA level in predicting HBV-related adverse events in patients with an HBV DNA level <2000 IU/mL. In the Asia Pacific region, where HBV genotypes B and C prevail, an HBsAg level ≤100 IU/mL has been shown to serve as a predictor of HBsAg loss over time. In HBeAg-negative patients with an HBV DNA level <2000 IU/mL, an HBsAg level >1000 IU/mL is associated with higher risks of hepatocellular carcinoma, cirrhosis, and HBeAg-negative hepatitis. European studies also indicated that combining levels of HBsAg <1000 IU/mL and HBV-DNA