Patient description: A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.

Clinical trial eligibility criteria: eligible ages (years): 18.0-70.0,  Hepatitis B Hepatitis, Viral Documented evidence of chronic HBV infection (eg, HBsAg positive for at least 6 months or HBV DNA positive for at least 6 months). In the absence of documented evidence of HBsAg or HBV DNA, the subject must be HBsAg positive, and anti-HBc (IgM) negative at Screening. 2. Not on any antiviral medications for at least 6 months. If a subject is HBeAg negative, they will be eligible if they have not received antiviral medications for at least 3 months. Antiviral medications lamivudine, telbivudine, adefovir, tenofovir, entecavir, IFN therapies of any type, and all other medications with potential antiviral activity. 3. HBV DNA > 2000 IU/mL for HBeAg-negative subjects and > 20000 IU/mL for HBeAg-positive subjects at Screening 4. ALT > ULN, but < 5 x the ULN and ≤ 200 U/L 5. Ultrasound, computed tomography (CT) scan, or magnetic resonance imaging (MRI) within 3 months of randomization date with no evidence of hepatocellular carcinoma 6. Must be willing and able to comply with all study requirements 7. Negative urine or serum pregnancy test (for women of childbearing potential [WOCBP]) documented within the 24-hour period prior to the first dose of test drug. If the urine pregnancy test is positive, a follow-up serum test is required for confirmation. Additionally, all fertile males with partners of childbearing age and females must be using reliable contraception during the study and for 3 months after treatment completion. All fertile males must also refrain from sperm donation while on IP and for 3 months after completion of IP. 8. Must have the ability to understand and sign a written ICF; consent must be obtained prior to initiation of study procedures for Extension Period: Subjects who meet all of the following may be eligible to be enrolled into the Extension Period: 1. Signed informed consent form 2. Subject was randomized in Part A or Part B  Subjects who meet any of the following are not to be enrolled in this study: 1. Any prior liver biopsy evidence of metavir F3 or F4 disease 2. Any history of decompensation of liver disease including history of ascites, encephalopathy, or varices 3. Evidence of cirrhosis as defined by Fibroscan at the Screening Visit of ≥ 8 kilopascals (kPa) or both a Fibrotest ≥ 0.65 and AST:platelet ratio index (APRI) ≥ 1.0 (subjects will not be excluded if only 1 of the Fibrotest or APRI result is higher than allowed) or have had evidence of Metavir F3-F4 on liver biopsy at any time. 4. Laboratory parameters not within defined thresholds: white blood cells (WBC) < 4000 cells/µL, (SI unit < 4.0 × 109/L), hemoglobin (HgB) < 12 g/dL (SI unit < 120 g/L) for females, < 13 g/dL (SI unit < 130 g/L) for males, platelets < 130,000 per µL, (SI unit < 130 × 109/L), albumin < 3.5 g/dL,(SI unit < 35 g/L), international normalized ratio (INR) > 1.5, total bilirubin > 1.2 mg/dL, (SI unit > 20.52 µmol/L), or alpha-fetoprotein (AFP) > 50 ng/mL (SI unit > 180.25 nmol/L). Subjects with an elevated indirect bilirubin and known Gilbert's disease can be included if direct bilirubin is within normal limits. Subjects with an AFP > 50 ng/mL but ˂ 500 ng/mL can be included if computed tomography (CT) scan or magnetic resonance imaging (MRI) performed within 3 months shows no evidence of hepatocellular carcinoma 5. Creatinine > 1.2 mg/dL, (SI unit > 106.08 µmol/L), creatinine clearance < 50 mL/min, (SI unit < 0.83 L/s/m2) 6. Co-infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or hepatitis D virus 7. Evidence or history of hepatocellular carcinoma 8. Malignancy within 5 years prior to Screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc). Subjects under evaluation for possible malignancy are not eligible. 9. Significant cardiovascular, pulmonary, or neurological disease 10. Received solid organ or bone marrow transplant 11. Received within 3 months of Screening or expected to receive prolonged therapy with immunomodulators (eg, corticosteroids) or biologics (eg, monoclonal antibody, IFN) 12. Subjects currently taking medication(s) that are transported through organic anion transporting polypeptide 1 (OATP1) including, but not limited to, atazanavir, rifampin, cyclosporine, eltrombopag, gemfibrozil, lopinavir/ritonavir, and saquinavir 13. Use of another investigational agent within 3 months of Screening 14. Current alcohol or substance abuse judged by the Investigator to potentially interfere with compliance 15. Females who are pregnant or may wish to become pregnant during the study 16. If the Investigator believes the prospective subject will not be able to comply with the requirements of the protocol and complete the study 17. Any medical condition, in the opinion of the Investigator, that could interfere with evaluation of the study objectives or safety of the subjects for Extension Period Subjects who meet any of the following are not to be enrolled into the Extension Period: 1. Any condition, comorbidity, or laboratory abnormality that, based on the package insert of tenofovir or in the opinion of the Investigator, excludes the subject 2. Subjects who were withdrawn from Part A or Part B due to an AE or serious adverse event (SAE) related to the use of tenofovir 3. Participation in any other interventional study 4. Subject fully terminated from Part A or Part B