Antiviral therapy is the most important method to slow and stop the progress of the disease in patients with chronic hepatitis B (CHB). Nucleoside (acid) analogues (NA) can Effectively suppress HBV replication, but it should be continue used and relapse would happen in most patients after withdrawal of therapy. However, long-term use of NA could induce viral resistance mutation lead to loss of efficacy. Interferon treatment can enhance specific and non-specific immune function in chronic hepatitis B patients, make patients get immune control to HBV infection and obtain sustained response after treatment. Thus the CHB patients on the treatment of NA should be stop NA treatment after interferon treatment. In this study, the effects of interferon treatment in CHB patients who were on the NA treatment and obtained HBsAg level≤250 IU/ml.

In this trial, patients who were CHB and treated with NA more than 6 months, still on the treatment and achieved HBsAg level ≤250 IU/ml with HBV DNA undetectable will be randomized enrolled into group A (Intervention group), in which patients switch to interferon therapy for 72 weeks, group B(control group), patients continue treated with NA for 72 weeks. Serum HBV DNA load, HBsAg/anti-HBs level, HBeAg/anti-HBe will be tested at enrollment and every 3 months during the treatment course. Parameters of Liver and kidney function, and liver ultrasound examination will be tested with intervals 1-3 months. The efficacies of interferon treatment were devalued by the rate of HBsAg clearance and decline of HBsAg levels on the 72 weeks of interferon treatment compared with control group.

Inclusion Criteria:

• patients who were chronic hepatitis B and had achieved HBsAg level ≤250 IU/ml on treatment of Nucleoside (acid) Analogues

Exclusion Criteria:

• Active consumption of alcohol and/or drugs
• Co-infection with human immunodeficiency virus, hepatitis C virus, or hepatitis D virus
• History of autoimmune hepatitis
• Psychiatric disease
• Evidence of neoplastic diseases of the liver