A Randomized Study to Assess the Loss of HbsAg After a 48-week Treatment Period With Pegylated Interferon Alpha 2a in Patients With Chronic Hepatitis B

The purpose of this study is to assess the loss of HbsAg after a 48-week pegylated interferon alpha 2a in patients with chronic hepatitis B (HBeAg negativation)

The purpose of this study is to provide a therapeutical alternative to the use of an extended or undeterminated duration of treatment with prolonged nucleoside (s)/nucleotide (s)analog (s).

The duration of administration is not consensual, and in most cases followed by a virological relapse, so that, the prolonged use could lead to the occurrence of viral resistance and mutations.

It is therefore expected that treatment with pegylated interferon for 48 weeks in patients with undetectable HBV DNA by analog(s) may increase and promotes the loss of HbsAg and then promotes HbsAg seroconversion. In the absence of cirrhosis, the loss of HbsAg at 6 months would allow the end of treatment

Eligibility Criteria:
Inclusion Criteria:

* Positive Hbs Ag
* Negative HbeAg
* Plasma HBV DNA undetectable at pre-inclusion ever since 12 months
* ALT less than or equal to 5 times the upper limit of normal
* Non cirrhotic or Not Decompensated Cirrhosis (Child Pugh \<7)
* Undetectable hepatocellular carcinoma in liver scan and / or alpha-fetoprotein rate \<50 ng / ml
* Unchanged nucleoside (s) and / or nucleotide (s) treatment for at least three months (and not including telbivudine)
* Negative pregnancy test for childbearing women
* Signed informed consent
* Use of contraception for childbearing women

Exclusion Criteria:

* Polymorphonuclear neutrophils \<1500/mm3
* Platelets \<70.000/mm3
* Co-infections with HIV, HCV and / or HDV
* Prolonged excessive consumption of alcohol
* Active intravenous drug addiction
* Immunomodulators Treatment(eg interferons), ever since one year
* Immunosuppressive treatments terminated ever since one year
* Telbivudine treatment
* Long course steroid treatment (more than 4 weeks) by oral way
* History of severe epilepsy or current use of anticonvulsants
* Severe heart disease (eg heart failure stage III or IV NYHA class, myocardial infarction less than 6 months, ventricular arrhythmia requiring treatment, unstable angina or other significant cardiovascular disease)
* Chronic liver disease other than HBV-related (hemochromatosis, autoimmune hepatitis, metabolic liver disease, including Wilson's disease and a deficiency of alpha1-antitrypsin deficiency, alcoholic liver disease, exposure to toxins)
* Presence or suspicion of cancer or a history of cancer (except basal cell carcinoma or in situ carcinoma) within 5 years preceding the randomization
* Thyroid uncontrolled disease, abnormal TSH, elevated thyroid antibodies and clinical manifestations of thyroid dysfunction
* History of autoimmune disease (inflammatory digestive, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis ....) Or presence of autoantibodies at a significant rate
* Renal impairment (creatinine clearance \<50 ml / min using the Cockroft formula), renal transplantation, hemodialysis
* Hypersensitivity to the active substance, interferon alpha or any component
* History of depression or psychiatric disorders and uncontrolled depression or uncontrolled psychiatric disorders
* Pregnancy or breastfeeding, or wish of pregnancy during the study period.
* Patients under legal protection or unable to express their consent