Inclusion Criteria:

• Male and female patients over 18 years of age
• Chronic hepatitis B, HBs Ag-positive for over 6 months, anti HBs negative
• Patients with HBeAg- negative chronic hepatitis B (CHB) and anti-HBe positive at screen
• Patients naïve to anti-HBV nucleoside or nucleotide and any other experimental nucleoside/nucleotide analog for HBV
• Serum HBV-DNA quantifiable over 2000 IU/mL at screening
• ALT over 1.25 ULN and below 10 ULN
• Liver biopsy (baseline or within prior 6 months) with evidence of chronic hepatic inflammatory injury (Metavir Activity score over 1 ; Knodell necroinflammatory score over 3, Ishak score over 1)

Exclusion Criteria:

• Cirrhosis or bridging fibrosis on liver biopsy
• Subjects who have received any form of alpha interferon in the past 6 months prior to the first administration of randomized treatment
• Any systemic anti-viral, anti-neoplastic or immuno-modulatory treatment (including supraphysiologic doses of steroids and radiation) below 6 months prior to the first dose of randomized treatment and during the study (except for below 10 days of acyclovir for herpetic lesions, or prednisone below 10 mg/days for below 10 days more than 1 month)
• Women with ongoing pregnancy or breast feeding
• Positive test at screening for anti-HAV IgM Ab, anti-HIV Ab, anti-HCV Ab, HCV RNA, anti-HDV Ab
• History or other evidence of a medical condition associated with chronic liver disease other than HBV (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease including Wilson's disease and alpha1-antitrypsin deficiency, alcoholic liver disease, toxin exposures, toxic thalassemia, NASH)
• History or other evidence of bleeding from esophageal varices or other clinical conditions consistent with decompensated liver disease (defined by one of the following criteria being met: serum albumin below 3.5 g/L, prothrombin time over 4 seconds prolonged, serum bilirubin over 34 µmol/L, history of encephalopathy, history of ascites)
• Neutrophil count below 1200 cells/mm3 or platelet count below 90,000 cells/mm3 at screening
• Serum creatinine level over 130µmol/l or calculated creatinine clearance below 70 ml/min (Cockcroft-Gault)
• Evidence or history of tubular nephropathy , Fanconi syndrom or hypophosphoremia.
• Evidence of drug abuse (including excessive alcohol consumption) within one year of study entry
• History of a severe seizure disorder or current anticonvulsant use
• History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis etc.)
• History of major organ transplantation with an existing functional graft
• History or other evidence of severe illness or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study
• Evidence of an active or suspected cancer or a history of malignancy where the risk of recurrence is over 20 % within 2 years
• Patients with a value of alpha-fetoprotein over 100 ng/mL are excluded, unless stability (less than 10 % increase) has been documented over at least the previous 3 months
• Patients included in another trial within 8 weeks prior to screening
• Inability or unwillingness to provide informed consent or abide by the requirements of the study Reassessments : If a patient fails to meet the above inclusion /exclusion criteria for a reason thought to be reversible, that patient may be reassessed for entry on two additional occasions at most. If the parameter out of range for inclusion was ALT over 10 x ULN, the patient should be reassessed over 4 weeks after the date corresponding to the value that was over 10 x ULN.