Augmenting Response to Entecavir With Peginterferon a-2a for the Treatment of HBeAg-positive Chronic Hepatitis B

Inclusion Criteria: * Chronic hepatitis B (HBsAg positive \> 6 months) * HBeAg positive, anti-HBe negative at screening * ALT \> 1.3 x ULN within 60 days prior to screening and during screening * Liver biopsy performed within 2 years prior to screening or during screening * Age \> 18 years * Written informed consent * Adequate contraception for males and females during treatment and follow up; negative pregnancy test (for women of childbearing potential) Exclusion Criteria: * Antiviral therapy against HBV within the previous 6 months * Treatment with any investigational drug within 30 days of screening * Previous treatment with lamivudine or telbivudine for more than six months * Severe hepatitis activity as documented by ALT\>10 x ULN * History of decompensated cirrhosis (defined as jaundice in the presence of cirrhosis, ascites, bleeding gastric or esophageal varices or encephalopathy) * Pre-existent neutropenia (neutrophils \< 1,500/mm3) or thrombocytopenia (platelets \< 90,000/mm3) * Co-infection with hepatitis C virus or human immunodeficiency virus (HIV) * Other acquired or inherited causes of liver disease (i.e. alcoholic liver disease, obesity induced liver disease, drug related liver disease, auto-immune hepatitis, hemochromatosis, Wilson's disease or alpha-1 antitrypsin deficiency) * Alpha fetoprotein \> 50 ng/ml * Hyper- or hypothyroidism (subjects requiring medication to maintain TSH levels in the normal range are eligible if all other inclusion/exclusion criteria are met) * Immune suppressive treatment within the previous 6 months * Contra-indications for alpha-interferon therapy like suspected hypersensitivity to interferon or PEG-interferon or any known pre-existing medical condition that could interfere with the patient's participation in and completion of the study. * Pregnancy, lactation * Other significant medical illness that might interfere with this study: significant pulmonary dysfunction in the previous 6 months, malignancy other than skin basocellular carcinoma in previous 5 years, immunodeficiency syndromes (e.g. HIV positivity, auto-immune diseases, organ transplants other than cornea and hair transplant) * Any medical condition requiring, or likely to require chronic systemic administration of steroids, during the course of the study * Substance abuse, such as alcohol (\> 80 g/day), I.V. drugs and inhaled drugs in the past 2 years. * Any other condition which in the opinion of the principal investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in and completing the study