Inclusion Criteria:

• Male or female subjects aged 18‑65 years inclusive
• Documented chronic hepatitis B infection determined by the presence of serum HBsAg for at least 6 months
• Documented HBeAg negative and HBeAb positive at the screening visit and with at least a 6 months history of HBeAg negativity.
• Serum HBV DNA ≥ 104 copies/mL (Roche COBAS AMPLICORTM HBV MONITOR Test, LLOD 300 copies/mL) at study screening (within 4 weeks before baseline)
• ALT value ≥1.3 times the upper limit of normal (ULN) at the time of screening, as determined using laboratory ranges and documented ALT abnormal within 6 month prior to the study screening.
• Serum alpha fetoprotein (AFP) < 50 ng/mL at the first screening visit. If the AFP level is ≥ 50 ng/mL but declined to < 50 ng/mL between screening and baseline, the patient is eligible.

• Compensated liver disease with the following laboratory and clinical parameters at study screening:

  • Prothrombin time ≤ 2 second above normal range.
  • Albumin ≥ 35 g/L.
  • Total bilirubin ≤ 2.5 mg/dL (≤ 43 µmol/L) or normal direct bilirubin.
  • No history of variceal bleeding.
  • No history of encephalopathy.
  • No history of ascites
  • Adequate renal function defined as serum creatinine ≤ 1.5 mg/dL (≤ 130 µmol/L).
  • Adequate hematological function defined as:
  • Absolute neutrophil count ≥ 1 x 10³/mm³ ( ≥ 1 x 10^9/L);
  • Platelets ≥ 80 x 10³/mm³ (≥ 80 x 10^9/L); Platelets ≥ 100 x 10³/mm³ ( ≥ 100 x 10^9/L) recommended for the patients who will undergo liver biopsy.
  • Hemoglobin ≥ 10 g/dL (≥ 100 g/L) (males) or ≥ 9 g/dL (≥ 9 g/L) (females).
  • Willing and able to undergo a minimum of two liver biopsies (prior to dosing, and after 104 weeks of therapy; only apply to subjects who are enrolled to the sites where liver biopsy is required).

  • A female is eligible to enter and participate in this study if she is of:

    1. non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is pre-menarchal or post-menopausal);
    2. child-bearing potential with a negative serum pregnancy test at screen, and agrees to one of the following: Complete abstinence from intercourse from 2 weeks prior to administration of the study drug, throughout the study, and for a time interval after completion or premature discontinuation from the study to account for elimination of the investigational drug, (a minimum of 5 half-lives or longer if the pharmacodynamic profile of the investigational drug warrants a longer time period); or, Female sterilization; or, Sterilization of male partner; or, Implants of levonorgestrel; or, Injectable progestogen; or, Oral contraceptive (combined or progestogen only); or, Any intrauterine device (IUD) with published data showing that the lowest expected failure rate is less than 1% per year (not all IUDs meet this criterion); or, Any other methods with published data showing that the lowest expected failure rate for that method is less than 1% per year; or, Barrier method only if used in combination with any of the above acceptable methods.
  • Agree not to participate in any other investigational trials or to undertake other HBV systemic antiviral regimens during participation in this study
  • Able to give written informed consent and comply with the requirements of the study

Exclusion Criteria:

• Any serious or active medical or psychiatric illnesses other than hepatitis B which, in the opinion of the investigator, would interfere with patient treatment, assessment or compliance with the protocol. This would include, may not limit to, renal, cardiac, pulmonary, vascular, neurogenic, digestive, metabolic (diabetes, thyroid disorders, adrenal disease), immunodeficiency disorders, active infection or cancer.
• Documented evidence of active liver disease due to other causes including co-infection hepatitis C (HCV), Subjects who are anti-HCV positive and in whom HCV RNA is undetectable are considered to be HCV seropositive and will not eligible; co-infection with hepatitis delta (HDV); co-infection with HIV; autoimmune hepatitis (antinuclear antibody titre > 1:160)
• Clinical signs of decompensated liver disease at baseline. These may include but are not limited to:

serum bilirubin > 2.5 mg/dL (≤ 43 µmol/L)

• prothrombin time > 2 second prolonged above ULN
• serum albumin < 35g/L

• history of ascites, variceal bleeding, or encephalopathy

  • Alanine aminotransferase (ALT) >10 times ULN at screening or history of acute exacerbation leading to transient decompensation
  • Hepatocellular carcinoma as evidenced by one of the following:
• suspicious foci on ultrasound or radiological examination

• - where no positive ultrasound finding, but serum alpha-fetoprotein > 100ng/mL

  • Active alcohol or drug abuse or history of alcohol or drug abuse considered by the investigator to be sufficient to hinder compliance with treatment, participation in the study or interpretation of results.
  • Use of immunosuppressive therapy, immunomodulatory therapy (including interferon or thymosin), systemic cytotoxic agents, chronic anti-viral agents excluding lamivudine (e.g. ganciclovir, adefovir dipivoxil, entecavir, famciclovir, FTC, DAPD, LFMAU, HBIg), Chinese herbal medicines known to have activity against HBV within the previous 12 months or during the study; use of agents with effect of ALT reduction (e.g. schisandra agents) during the study
  • Use of lamivudine within the previous 3 months or during the study
  • Planned for liver transplantation or previous liver transplantation
  • Received hepatotoxic drugs (e.g., anabolic steroids, ketaconazole, itraconazole, isoniazid, rifampin, rifabutin) within 2 months prior to study screening or expected to receive these during the course of the study.
  • Received nephrotoxic drugs (e.g., aminoglycosides, amphotericin B, vancomycin, cidofovir, foscarnet, cis-platinum, pentamidine etc.) or competitors of renal excretion (e.g., probenecid) within 2 months prior to study screening or the expectation that patient will receive any of these during the course of the study.
  • Receiving systemic (intravenous or oral) steroids, immuno-suppressant therapies or chemotherapeutic agents within 2 months of study screening or expected to receive these agents during the course of the study.
  • History of hypersensitivity to nucleoside and/or nucleotide analogues.
  • Inability to comply with study requirements.
  • Lactating females or females with a positive serum pregnancy test.
  • Organ or bone marrow transplant recipients.
  • Previous (or planned) participation in an investigational trial involving administration of investigational compound within 2 months prior to the study screening.
  • Can not comply with the requirements of the study