a study of switch from nucleotide to peginterferon alfa-2a in chb patients achieving hbeag loss and hbv dna <200iu/ml

Conditions: Chronic Hepatitis B

Summary: a randomized, open-label, multicenter study. the patients after 1-3 years nas treatment and having achieved hbeag loss and hbv dna \<200iu/ml will be switched to pegasys for 48 or 96 weeks (with a 12 weeks period of overlap with the na for safety reasons). the subjects will be randomized into 2 groups: group 1 : 48-week standard treatment by peginterferon alfa 2a 180µg/week group 2 : 96-week prolonged treatment by peginterferon alfa 2a 180µg/week. all the patients will be followed up for 48 weeks after discontinuation of the study medication. note: nas will be stratified lam, etv and adv, with the ratio 1:1:1.

eligibility criteria: men and women old of 18 to 65 years with chronic hepatitis b hbeag positive treated with nucleoside and/or nucleotide analogues for 1-2 years and with partial response (hbeag loss and hbv dna \<1000copies/ml).

Eligibility criteria:
inclusion criteria: * patients on-treatment with nas (adv, etv or lam) for 1-3 years, having achieved hbeag loss at screening, and hbv dna \<200iu/ml for at least 48 weeks * male and female patients ≥ 18 to 65 years of age * chronic hepatitis b (positive hbsag for at least 6 months prior to na therapy start) * compensated liver disease (child-pugh \<6) * absence of hepatocellular carcinoma on liver imaging and/or alfa fetoprotein \< 50 ng/ml * negative urine or blood pregnancy test for women of childbearing potential within 24 hours of first peg ifn study medication administration * able and willing to provide informed consent and abide by the requirements of the study exclusion criteria: * neutrophil count \<1.5 x 109cells/l or platelet count \<90 x 109cells/l * co-infections with hiv, hav, hcv, hdv or hev * women with ongoing pregnancy or breast feeding, or wishing to become pregnant during the study period * prolonged and excessive alcohol intake (\> 40g/day for men and \> 30g/day for women) * active intravenous drug abuse * history or current treatment with telbivudine * treatment with immunomodulators (e.g. interferon) for less than one year before study enrollment * treatment with immunosuppressors (including systemic corticosteroids) or anti-neoplastic treatment (including radiation therapy) \<=6 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study * serum concentrations of ceruloplasmin or alfa-antitrypsin consistent with an increased risk of metabolic disease * history or other evidence of chronic pulmonary disease associated with functional limitation * history of severe cardiac disease * history of the severe seizure disorder or current anticonvulsivant use * history of thyroid disease poorly controlled on prescribed medications. patients with elevated thyroid stimulating hormone concentrations with elevation of antibodies to thyroid peroxidase and any clinical manifestations of thyroid disease * history or other evidence of severe retinopathy * history of autoimmune disease or presence of a significant level of auto-antibodies * renal insufficiency (creatinine clearance of \< 50 ml/min according to the cockroft and gault equation), kidney transplant, hemodialysis * history of depression or uncontrolled psychiatric disorders * subjects protected by law or not in a position to give consent * patients with reproductive potential not willing to use an effective method of contraception. * evidence of an active or suspected cancer or a history of malignancy (other than basocellular carcinoma or in-situ cervical carcinoma)

Keywords: nucleoside peginterferon alfa-2a