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

Tai-Chung Tseng^{a, b, c}, Jia-Horng Kao^{b, d, e, f}

^a Division of Gastroenterology, Department of Internal Medicine, Buddhist Tzu Chi General Hospital, Taipei Branch, New Taipei, Taiwan
^b Graduate Institute of Clinical Medicine, National Taiwan University, College of Medicine, Taipei, Taiwan
^c School of Medicine, Tzu Chi University, Hualien, Taiwan
^d Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
^e Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
^f Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan

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Abstract
Quantification 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 <2000 IU/mL aids in identifying true inactive carriers in genotype D HBeAg-negative carriers. All this evidence highlights the evolution of viral biomarkers in predicting the prognosis of CHB. Quantitative HBsAg can complement HBV DNA in optimizing the management of CHB patients in clinical practice.

Keywords
HBsAg; HBV; HCC; Hepatitis; qHBsAg