48 Weeks Combination Therapy for Patients With HBeAg-negative Chronic Hepatitis B Virus (HBV) Infection

Inclusion Criteria:

• Chronic hepatitis B
• Biopsy performed within one year prior to screening or during screening
• ALT > 1.5 x ULN
• HBeAg negative, anti-HBeAg positive
• HBV DNA > 10E5 copies/ml
• Age 18-70 years
• Written informed consent
• Hepatic imaging without evidence of HCC
• All fertile males and females must be using two forms of effective contraception

Exclusion Criteria:

• Antiviral therapy against HBV within the previous 6 months; treatment with any investigational drug within 30 days of entry to this protocol
• Severe hepatitis activity as documented by ALT > 10 x ULN
• Advanced liver disease
• Pre-existent leucopenia or thrombopenia
• Co-infection with HCV,HDV or HIV
• Other acquired or inherited causes of liver disease
• Alpha fetoprotein > 50 ng/ml.
• Evidence of severe renal disease
• Hyper- or hypothyroidism
• Significant cardiovascular or pulmonary dysfunction, malignancy,immunodeficiency syndromes
• Immune suppressive treatment within the previous 6 months
• Contra-indications for alpha-interferon therapy
• Pregnancy, breast-feeding
• Any medical condition requiring chronic systemic administration of steroids
• Substance alcohol or drug abuse
• Subjects with clinically significant retinal abnormalities
• Subjects with clinically significant hearing abnormalities
• Hemoglobinopathies
• Subjects with known hypersensitivity to ribavirin