Pegylated interferon alfa-2a (PEG-IFN) may induce sustained virological response (SVR) inS ubstantial advances have been made in the treatment of chronic hepatitis B (CHB) in the past decade. Several nucleos(t)ide analogues are currently approved for the treatment of hepatitis B virus (HBV) infection with a high efficacy in suppressing HBV replication. However, a long duration of treatment is needed to maintain viral suppression, and the major question of whether oral therapy can ever be stopped remains unanswered. 1 In parallel with analogues, the American Association for the Study of Liver Diseases practice guidelines have advocated pegylated interferon alfa-2a (PEG-IFN) as a potential first-line therapy in hepatitis B e antigen (HBeAg)-negative patients. 2 The advantages of PEG-IFN therapy include a limited treatment course, a high rate of HBeAg seroconversion (in HBeAg-positive patients), a 20% to 30% rate of sustained virological response (SVR), the potential for hepatitis B surface antigen (HBsAg) loss or seroconversion, and a lack of resistance development. 3 Nonetheless, the use of PEG-IFN currently accounts for

Quantitative HBsAg had been suggested to be helpful in management of HBV, but assays were cumbersome. The recent availability of commercial quantitative assays has restarted the interest in quantitative serum hepatitis B surface antigen (HBsAg) as a biomarker for prognosis and treatment response in chronic hepatitis B. HBsAg level reflects the transcriptional activity of cccDNA rather than the absolute amount of cccDNA copies. Serum HBsAg level tends to be higher in hepatitis B e antigen (HBeAg)-positive than HBeAg-negative patients. Among patients with a low HBV DNA (<2000IU/ml), HBsAg <1000IU/ml in genotype D HBV infection and HBsAg <100IU/ml in genotype B/C HBV infection is associated with inactive carrier state in HBeAg-negative patients. The HBsAg reduction by nucleos(t)ide analogues (NA) is not as pronounced as by interferon treatment. On peginterferon treatment, sustained responders tend to show greater HBsAg decline than the non-responders. The optimal on-treatment HBsAg cutoff to predict response needs further evaluation in HBeAg-positive patients, but an absence of HBsAg decline together with a <2 log reduction in HBV DNA at week 12 can serve as stopping rule in HBeAg-negative patients with genotype D HBV infection. A rapid serum HBsAg decline during NA therapy may identify patients who will clear HBsAg in the long-term. There are early reports among Asian patients that an HBsAg level of <100IU/ml might predict lower risk of relapse after stopping NA treatment. In clinical practice, serum HBsAg level should be used together with, but not as a substitute for, HBV DNA.