HBsAg Quantification in Clinical Practice

Several standardized commercial assays for quantification of hepatitis B surface antigen (qHBsAg) are now available. Studies on HBsAg kinetics from Asia and Europe have demonstrated that HBsAg levels are highest during the immune-tolerant phase, become lower during immune-clearance phase and are the lowest in hepatitis B ‘e’ antigen (HBeAg)-negative inactive low-replicative phase with a rise during HBeAg-negative chronic hepatitis B (CHB). Combined use of hepatitis B virus-deoxyribonucleic acid (HBV-DNA) and HBsAg levels may help in differentiating true inactive carrier state from HBeAg-negative CHB. Several retrospective studies have demonstrated a role for decline in HBsAg level for predicting response and nonresponse to therapy. In HBeAg-positive patients treated with pegylated-interferon (PEG-IFN), a lack of decline of qHBsAg at week 12 predicts nonresponders while a decline of qHBsAg at week 24 predicts responders to PEG-IFN. In HBeAg-negative patients, if at week 12, there is no decline in qHBsAg and the HBV-DNA decline is < 2 log, the patient is unlikely to respond, then stopping of PEG-IFN should be considered. With nucleos(t)ide analogs, the decline in HBsAg is lower than that with PEG-IFN and more marked in patients with HBeAg-positive chronic hepatitis, with elevated alanine aminotransaminase (ALT), thus suggesting that active immune response against HBV is required to lower HBsAg. In patients with HBeAg-negative chronic hepatitis, fall in HBsAg may help in developing stopping rules to reduce the need for lifelong therapy. Information provided by HBsAg is complementary to HBV-DNA and cannot replace the same. Prospective studies on HBsAg kinetics from all regions of the world are required to define optimum time of testing and cutoff levels before stopping rules can be recommended.