The study is designed to evaluate and compare the safety and tolerability of tenofovir disoproxil fumarate (DF), emtricitabine/tenofovir DF, and entecavir in the treatment of hepatitis B patients with decompensated liver disease.

Safety will be assessed by evaluating adverse events, laboratory abnormalities and the development of drug-resistant mutations. Efficacy will be evaluated for reductions in Child-Pugh-Turcotte (CPT) and Model for End Stage Liver Disease (MELD) scores, reductions in HBV DNA, changes in liver enzymes, and the generation of antibody to virus.

• Drug: tenofovir disoproxil fumarate
• Drug: emtricitabine / tenofovir disoproxil fumarate
• Drug: entecavir

• Experimental:

  tenofovir disoproxil fumarate

  300 mg tablet, once-daily

• Experimental:

  emtricitabine / tenofovir disoproxil fumarate

  200 mg tablet / 300 mg tablet, once daily (combination pill)

• Experimental:

  entecavir

  0.5 or 1 mg tablet, once daily

Inclusion Criteria:

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

• Chronic Hepatitis B infection.
• 18 through 69 years of age, inclusive.
• HBV DNA >/= 1000 copies/mL.

• Decompensated liver disease with all of the following:

  • CPT score of 7-12 (inclusive) OR a past history of CPT score >/= 7 and any CPT at screen </= 12.
  • Serum ALT < 10 x ULN.
  • Hemoglobin >/= 7.5 g/dL.
  • Total WBC count >/= 1,500/mm3.
  • Platelet count >/= 30,000/mm3.
• Alpha-fetoprotein </= 20 ng/mL and ultrasound or other imaging with no evidence of HCC, or alpha-fetoprotein of 21-50 ng/mL and CT/MRI with no evidence of HCC, within 6 months of screening.
• Calculated creatinine clearance >/= 50 mL/min.
• Negative HIV, HCV and HDV serologies.
• Less than 24 months of total prior adefovir dipivoxil exposure.

Exclusion Criteria:

A patient who meets any of the following exclusion criteria cannot be enrolled in the study:

• Pregnant women, women who are breastfeeding or 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.
• Prior use of tenofovir DF or entecavir.
• History of variceal bleeding, hepatorenal syndrome, Grade 3 or Grade 4 hepatic encephalopathy, or spontaneous bacterial peritonitis within 60 days of screening.
• Grade 2 hepatic encephalopathy at screening
• History of solid organ or bone marrow transplant.
• Current use of hepatotoxic drugs, nephrotoxic drugs, or drugs that interfere with renal tubular secretion.
• Current therapy with immunomodulators (e.g., corticosteroids, IL-2, etc) or investigational drugs.
• Diagnosis of proximal tubulopathy.
• Use of investigational agent within 30 days prior to screening.