This study will compare monotherapy with tenofovir to sequential therapy with pegylated interferon alpha-2b (pegIFN-2b) followed by tenofovir, and to combination therapy with pegIFN-2b + tenofovir, in participants with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B and elevated alanine aminotransferase (ALT). All enrolled participants will be be administered tenofovir alone for 8 weeks and then will be randomly assigned to 1 of the 3 treatment arms.

Inclusion Criteria:

• Chronic hepatitis B (hepatitis B surface antigen [HBsAg]-positive for >6 months or evidence of chronic hepatitis B in liver biopsy)
• Elevated serum ALT level
• Liver biopsy or a non-invasive investigation within 12 months prior to randomization with Chronic Hepatitis B
• Treatment naïve or history of interferon for not more than 1 month, taken at least 6 months before enrollment
• Compensated liver disease

Exclusion Criteria:

• Known hypersensitivity to tenofovir, interferon alpha-2b, and/or any other component of the study products
• Co-infection with hepatitis C virus (HCV), hepatitis D virus (HDV) or human immunodeficiency virus (HIV)
• Need for prolonged or frequent use of systemic acyclovir or famciclovir
• Previously received lamivudine or an investigational anti-hepatitis B virus (HBV) nucleoside or nucleotide analog and were resistant to these drugs
• History of variceal bleeding or other GI bleeding due to portal hypertension, hepatic encephalopathy, spontaneous bacterial peritonitis, Grade III and IV esophageal varices unless banded or other clinical signs of hepatic decompensation
• History of hepatocellular carcinoma (HCC) or findings suggestive of possible HCC
• Need for potentially hepatotoxic drugs (e.g. dapsone, erythromycin, fluconazole, ketoconazole, rifampin, and anti-tuberculosis regimens) or nephrotoxic drugs (e.g. frequent nonsteroidal anti-inflammatories, aminoglycosides, amphotericin B, and foscarnet)
• One or more additional known primary or secondary causes of liver disease, other than hepatitis B
• History of clinical pancreatitis
• Pregnant or breastfeeding
• Female participants of childbearing potential and male participants must be willing to use acceptable method of birth control.
• Medical condition that requires frequent or prolonged use of systemic corticosteroids
• Use of warfarin or other anticoagulants during 30 days prior to screening or if expected to be needed during the study period