Inclusion Criteria:

A patient must meet all of the following inclusion criteria to be eligible for participation in this study:

• Chronic HBV infection, defined as positive serum HBsAg for at least 6 months.
• 18 through 69 years of age, inclusive.

• Active HBeAg negative chronic HBV infection, with all of the following:

  • HBeAg negative and HBeAb positive at screening;
  • ALT levels > ULN and </= 10 x ULN;
  • serum HBV DNA > 100,000 copies/mL at screening;
  • creatinine clearance >/= 70 mL/min;
  • hemoglobin >/= 8 g/dL;
  • neutrophils >/= 1,000 /mL.
• Knodell necroinflammatory score >/= 3 and a Knodell fibrosis score < 4. However, up to 120 patients with cirrhosis, i.e., a Knodell fibrosis score equal to 4, will be eligible for enrollment.
• Negative serum β-HCG
• Nucleotide naïve, i.e., no prior nucleotide (tenofovir DF or adefovir dipivoxil) therapy for greater than 12 weeks.
• Nucleoside naïve, i.e., no prior nucleoside (any nucleoside) therapy for greater than 12 weeks. However, up to 120 patients with greater than 12 weeks prior lamivudine experience will be eligible.
• Willing and able to provide written informed consent.
• Had a liver biopsy performed within 6 months of baseline and has readable biopsy slides or agrees to have a biopsy performed prior to baseline

Exclusion Criteria:

• Pregnant women, women who are breast feeding, or women who believe they may wish to become pregnant during the course of the study
• Males and females of reproductive potential who are unwilling to use an "effective" method of contraception during the study.
• Decompensated liver disease defined as conjugated bilirubin > 1.5 x ULN, PT > 1.5 x ULN, platelets < 75,000/mL, serum albumin < 3.0 g/dL, or prior history of clinical hepatic decompensation (e.g., ascites, jaundice, encephalopathy, variceal hemorrhage)
• Received any nucleoside, nucleotide (tenofovir DF or adefovir dipivoxil) or interferon (pegylated or not) therapy within 6 months prior to the pre treatment biopsy
• Evidence of hepatocellular carcinoma (HCC)
• Coinfection with hepatitis C virus (HCV), HIV, or hepatitis D virus (HDV)
• Significant renal, cardiovascular, pulmonary, or neurological disease
• Received solid organ or bone marrow transplantation
• Is currently receiving therapy with immunomodulators (e.g., corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion
• Has proximal tubulopathy