Pegylated Interferon Alfa-2b Plus Ribavirin in Chronic Hepatitis B and Delta

Inclusion Criteria:

• Be positive for both anti-HDV and HBsAg for more than 6 months
• Present with elevated serum ALT levels at least 1.5 times the upper limit of normal, documented on two occasions (at least one month apart), within six months prior to enrollment
• Be HDV RNA positive by PCR (sensitivity: 103 copies/mL) [Yamashiro et al, 2004]
• Be HBV DNA positive by PCR
• Present with liver biopsy findings compatible with the diagnosis of chronic liver disease (the liver biopsy needs to be taken within 52 weeks prior to enrollment)
• Have adequate liver reserve (defined as equal to or better than Child-Pugh Class A)
• Present with WBC ≥3000/mm3, ANC ≥1500/mm3, and platelet ≥80,000/mm3
• Be able to and likely to attend regularly for treatment and follow-up
• Give their written informed consent
• Be negative for urine pregnancy test (for females of childbearing potential), documented once within the screening period and again within 24 hours prior to the first dose of study drug
• All male patients with female partners of childbearing age should use a barrier method of contraception
• All female patients of childbearing potential must use two reliable forms of effective contraception

Exclusion Criteria:

• Drug addicts or have any history or histological evidence of alcohol abuse, or currently receive prescriptions that may cause hepatotoxicity
• Have decompensated cirrhosis as coded by Child-Pugh classification (i.e. history of ascites, history of bleeding from esophageal varices, severe portal hypertension, serum albumin <30 g/l, serum bilirubin >30 mg/l)
• Present with WBC <3000/mm3, ANC <1500/mm3, or platelets <90,000/mm3
• Present with hemoglobin <12.0 gm/dl for female and <13.0 gm/dl for male
• Have been treated with immunosuppressive therapy within the past six months (e.g. steroids, azathioprine, cyclophosphamide)
• Have renal insufficiency (serum creatinine >150 μmol/l)
• Have clotting abnormalities which preclude a liver biopsy
• Have evidence of any serious neurological dysfunction
• Have obesity or diabetes mellitus-induced liver disease
• Have serological evidence of autoimmune chronic liver disease (e.g. antinuclear antibody titers >1:320, and/or smooth muscle antibody titers>1:160)
• Hemophiliacs
• Have evidence of inheritable disorders such as haemochromatosis, alpha-1-antitrypsin deficiency or Wilson's disease
• Have been exposed to hepatotoxic substances which might be the cause of hepatitis
• Pregnant, lactating or not practicing an adequate form of birth control, such as oral contraceptives or intrauterine devices
• Seropositive for anti-HIV or anti-HCV
• Have serious psychological or psychiatric problems disrupting daily activities
• Have AFP (alpha-fetoprotein) greater than 20 ng/ml; in case of elevated AFP, abdomen ultrasonography is required to exclude the possibility of HCC
• Have serious heart diseases (coronary heart disease, etc)
• Have a history of asthma or drug allergy which may lead to hypersensitivity to ribavirin