AIM: To examine the association between interferon(IFN) therapy and loss of hepatitis B surface antigen(HBs Ag) in inactive HBs Ag carriers. METHODS: This was a retrospective cohort study in inactive HBs Ag carriers, who were treatment-naive, with a serum HBs Ag level < 100 IU/m L and an undetectable hepatitis B virus(HBV) DNA level(< 100 IU/m L). All the 20 treated patients received subcutaneous PEG-IFN alfa-2a 180 μg/wk for 72 wk and were then followed for 24 wk. There were 40 untreated controls matched with 96 wk of observation. Serum HBs Ag, HBV DNA, and alanine aminotransferases were monitored every 3 mo in the treatment group and every 3-6 mo in the control group. RESULTS: Thirteen(65.0%) of 20 treated patients achieved HBs Ag loss, 12 of whom achieved HBs Ag seroconversion. Mean HBs Ag level in treated patients decreased to 6.69 ± 13.04 IU/m L after 24 wk of treatment from a baseline level of 26.22 ± 33.00 IU/m L. Serum HBV DNA level remained undetectable(< 100 IU/m L) in all treated patients during the study. HBs Ag level of the control group decreased from 25.72 ± 25.58 IU/m L at baseline to 17.11 ± 21.62 IU/m L at week 96(P = 0.108). In the control group, no patient experienced HBs Ag loss/seroconversion, and two(5.0%) developed HBV reactivation.CONCLUSION: IFN treatment results in HBs Ag loss and seroconversion in a considerable proportion of inactive HBs Ag carriers with low HBs Ag concentrations. METHODS: This was a retrospective cohort study in inactive HBs Ag carriers, who were treatment-naive, with a serum HBsAg level <100 IU / mL and an undetectable hepatitis B virus (HBV) DNA level (<100 IU / mL). All the 20 treated patients received subcutaneous PEG-IFN alfa-2a 180 μg / wk and were then followed for 24 wk. There were 40 untreated controls matched with 96 wk of observation. Serum HBs Ag, HBV DNA, and alanine aminotransferases were monitored every 3 mo in the treatment group and every 3-6 mo in the control group Mean HBs Ag level in treated patients decreased to 6.69 ± 13.04 IU / m L after 24 wk of treatment from a baseline level (65.0%) of 20 treated patients achieved HBs Ag loss, 12 of whom achieved HBs Ag seroconversion. of 26.22 ± 33.00 IU / m L. Serum HBV DNA level showed undetectable (<100 IU / mL) in all HBs Ag level of the control group decreased from 25.72 ± 25.58 IU / m L at baseline to 17.11 ± 21.62 IU / m L at week 96 (P = 0.108). In the control group, no patient experienced HBs Ag loss / seroconversion, and two (5.0%) developed HBV reactivation. CONCLUSION: IFN treatment results in HBs Ag loss and seroconversion in a proportion of inactive HBs Ag carriers with low HBs Ag concentrations.