Background: In the OSST study, hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients who switched from long-term entecavir (ETV) therapy to pegylated interferon-alpha 2a (PEG-IFN-alpha 2a; 40 kDa) achieved higher rates of HBeAg seroconversion and hepatitis B surface antigen (HBsAg) loss than those who continued ETV. Herein we report the sustainability of serological responses during 1 year of untreated follow-up in patients who switched from ETV to PEGIFN-alpha 2a therapy. Methods: A total of 62 patients who completed 48 weeks of PEG-IFN-alpha 2a therapy were followed-up for 48 weeks off treatment. Primary end points were HBeAg seroconversion and maintenance of HBeAg seroconversion at 48 weeks post-treatment. Secondary end points included HBsAg loss, HBV DNA < 1,000 copies/ml and alanine aminotransferase normalization (< 1x upper limit of normal). Results: The HBeAg seroconversion rate increased from 17.7% (11/62) at the end of treatment to 38.7% (24/62) 1 year post-treatment. Sustained HBeAg seroconversion was achieved by 63.6% (7/11) patients with end-of-treatment responses, while late HBeAg seroconversion was achieved by 33.3% (17/51) of patients who did not have end-of-treatment responses. Sustained HBsAg loss was documented in 6 of 7 patients, and sustained HBV DNA suppression was achieved in 60% (27/45) of patients with an end-of-treatment response. Conclusions: In patients who do not achieve HBeAg seroconversion during long-term ETV therapy, switching to finite treatment with PEG-IFN-alpha 2a produces HBeAg seroconversion in a substantial proportion of patients at end of treatment and during 1 year of follow-up. Moreover, HBeAg seroconversion and HBsAg loss are sustained in most patients during 1 year of untreated follow-up.