Hepatitis B interferon treatment is going to have a chance of re-positive. Interferon (IFN) has antiviral, antiproliferative, and immunomodulatory effects.IFN-α and IFN-β are primarily antiviral; while IFN-γ has a more significant immunomodulatory effect but weaker antiviral activity. Response to interferon therapy is characterized by suppression of HBV DNA and disappearance of HBeAg (in patients who are initially HBeAg positive). Most responders are able to maintain their virologic response during a follow-up period of 5-10 years after cessation of therapy, unless immune impairment occurs. One of the large long-term follow-up studies included 165 HBeAg-positive chronically HBV-infected patients who were treated with IFN between 1978 and 2002. Treatment response was defined as disappearance of HBeAg within 12 months after the end of treatment. The median follow-up of patients was 8.8 years. 54 patients (33%) responded. Only 7 (13%) responders relapsed. This shows that recurrence is still possible after interferon therapy. Patients treated with IFN should be evaluated for evidence of toxicity during and at the end of treatment, as well as for virologic, serologic, and biochemical responses. I am generally monitored at weeks 4, 12, 24, 36, and 48 during treatment and at 12, 24, and 48 weeks after treatment.