As HBsAg clearance is uncommon in chronic hepatitis B (CHB) patients on nucleoside analogues (NAs) therapy. The purpose of this study is to optimize HBsAg clearance in CHB Patients with sequential treatment of pegylated interferon alpha-2b and NAs.

CHB Patients who had received, and responded to, NAs for more than 12 months are switched to receive peginterferon alfa-2b 80 micrograms/week for 48 weeks and follow up for 48 weeks.

Inclusion Criteria:

1. CHB patients who had received NAs for more than 12 months.
2. Hepatitis B e antigen (HBeAg)-negative and anti-HBeAg positive.
3. Hepatitis B surface antigen (HBsAg) positive and <1500 IU/mL.
4. Hepatitis B virus DNA not detectable.

Exclusion Criteria:

1. Patients with liver cirrhosis, Hepatocellular Carcinoma or other malignancies.
2. Patients with other factors causing liver diseases.
3. Pregnant and lactating women.
4. Patients with concomitant HIV infection or congenital immune deficiency diseases.
5. Patients with diabetes, autoimmune diseases.
6. Patients with important organ dysfunctions.
7. Patients with serious complications ( e.g., infection, hepatic encephalopathy, hepatorenal syndrome, gastrointestinal bleeding. )
8. Patients who receive antineoplastic or immunomodulatory therapy in the past 12 months.
9. Patients who can't come back to clinic for follow-up on schedule.