Lamivudine and Adefovir to Treat Chronic Hepatitis B

• INCLUSION CRITERIA:

Age greater than 18 years and above, male or female

Known serum HBsAg positivity for at least 6 months

Detectable HBV-DNA in serum above 1 million copies per ml, as detected by quantitative PCR (Roche Cobas Assay)

Serum ALT (alanine aminotransferase) or AST (aspartate aminotransferase)levels above the upper limit of normal based on two determinations taken at least one month apart during the 6 months before entry

Liver biopsy within 2 years consistent with chronic hepatitis and with a histology activity index score (HAI) of 6 or more (out of a total possible score of 22) and an "Ishak" fibrosis score of at least 1 (out of a total possible score of 6). For patients with lamivudine resistance the liver biopsy may be performed either on or off lamivudine.

Written informed consent.

EXCLUSION CRITERIA

Previous or current treatment with adefovir or tenofovir.

Co-infection with HDV (Hepatitis D Virus) as defined by the presence of both anti-HDV in serum and HDV antigen in liver

Co-infection with HCV (Hepatitis C Virus) as defined by the presence of both anti-HCV and HCV RNA in serum.

Co-infection with HIV (Human immunodeficiency virus) as defined by the presence of anti-HIV in serum.

Decompensated liver disease as defined by serum bilirubin greater than 2.5 mg%, prothrombin time of greater than 2 seconds prolonged, a serum albumin of less than 3.0 gm%, or a history of ascites, variceal bleeding, or hepatic encephalopathy.

Presence of other causes of liver disease (i.e., hemochromatosis, Wilson's disease, alcoholic liver disease, non-alcoholic steatohepatitis, alpha-1 antitrypsin deficiency)

A history of organ transplantation or in the absence of organ transplantation, any immunosuppressive therapy requiring the use of more than 5 mg of prednisone (or its equivalent) daily.

Significant systemic illnesses other than liver diseases including congestive heart failure, renal failure, chronic pancreatitis, diabetes mellitus with poor control that in the opinion of the investigators might interfere with therapy.

Pregnancy or inability to practice contraception in patients capable of bearing or fathering children

Pre-existing bone marrow suppression: White Blood Cells (WBC) less than 2,000 cells/mm(3), hematocrit less than 30%, or platelets less than 50,000 cells/mm(3).

History of clinically apparent pancreatitis or evidence of subclinical pancreatitis as shown by serum amylase values twice the upper limits of the normal range and abnormalities of the pancreas on CT or other imaging studies of the abdomen

Prior interferon treatment within 6 months of entry

Sensory or motor neuropathy apparent from medical history and physical examination

Creatinine clearance less than 50 ml/min or serum creatinine greater than 1.5 mg/dl; creatinine clearance will be determined on a 24 hour urine specimen. Accuracy of collection will be ensured by documenting appropriate total creatinine excretion in the 24 hour urine specimen (15 mg/kg) and correcting for the patient's age and gender.

Concurrent use of nephrotoxic agents (e.g., aminoglycosides, amphotericin B, vancomycin, foscarnet, cis-platinum, pentamidine, nonsteroidal anti-inflammatory agents) or competitors of renal tubular excretion (e.g., probenecid) within 2 months prior to study screening or the expectation that the subject will receive these during the course of the study

History of hypersensitivity to nucleoside/nucleotide analogues

Active ethanol/drug abuse/psychiatric problems that, in the investigator's opinion, might interfere with participation in the study

History of seizure disorder

History of renal tubular acidosis

History of malignancy or treatment for a malignancy within the past 5 years