This study proposes to compare the effect of 48 weeks exposure to pegylated interferon alpha vs. nucleoside analogue (NA) on hepatitis B e antigen (HBeAg) seroconversion and HBsAg levels in nucleoside analogue controlled HBeAg-positive chronic hepatitis B (CHB) patients who have an undetectable hepatitis B virus (HBV) viral load at least 1 years.

Pegylated interferon after long term NA therapy will potentiate the antiviral efficacy directly via its effect on broad antiviral activities and indirectly via activation of innate and adaptive immune responses leading to HBeAg seroconversion and eventually HBsAg loss and/or seroconversion.

This study proposes to compare the effect of 48 weeks exposure to pegylated interferon alpha vs. NA on HBeAg seroconversion and HBsAg levels in NA controlled HBeAg-positive CHB patients who have an undetectable HBV viral load at least 1 years.

Inclusion Criteria:

• Informed consent
• Age over 20 years
• HBeAg-positive CHB patients
• Patients treated with all available nucleoside analogue monotherapy or combination in Korea except telbivudine ( e.g.entecavir monotherapy or lamivudine/adefovir combination , lamivudine, adefovir monotherapy) for ≥ 18months and patients who have undetectable HBV viral load at least one year HBV DNA undetectable (≤ 400 copies/ml ) Serum alanine transferase: ≤ 10 X upper limit of normal (ULN) Baseline HBsAg: ≥ 102 IU/ml
• Negative urine or serum pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of test drug. Additionally, all fertile males with partners of childbearing age and females must be using reliable contraception during the study and for 3 months after treatment completion.
• Obtaining written informed consent form

Exclusion Criteria:

• Decompensated cirrhosis or other contraindications to interferon alfa 2a therapy following local label.
• Concomitant or prior use of telbivudine.
• Positive test at screening for hepatitis A virus immunoglobulin M Ab, Hepatitis C virus-RNA or hepatitis C virus Ab, hepatitis delta virus Ab or HIV Ab.
• Diagnosed hepatic cellular carcinoma
• Any evidence of decompensated liver disease (Childs B-C)
• History or other evidence of a medical condition associated with chronic liver disease (e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposures, thalassemia).
• Women with ongoing pregnancy or who are breast feeding.
• Evidence of alcohol and/or drug abuse within one year of entry.
• History of major organ transplantation with an existing functional graft.
• Inability or unwillingness to provide informed consent or abide by the requirements of the study.
• History or other evidence of severe illness or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study.
• Patients with a value of alpha-fetoprotein >100 ng/mL are excluded, unless stability (less than 10% increase) has been documented over at least the previous 3 months.
• patients having hypersensitivities for peginterferon alfa-2a or NAs