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): 18.0-60.0,  Hepatitis B Chronic Hepatitis B Viral Hepatitis B Main for All Subjects: 1. Subject has provided written consent. 2. In the investigator's opinion, the subject is able to understand and comply with protocol requirements, instructions, and study restrictions and is likely to complete the study as planned. 3. Subject is in good health as deemed by the investigator, based on the totality of findings following a medical evaluation, including medical history, physical examination, laboratory tests and ECG. 4. Male or female, 18-60 years of age. 5. Body mass index 18-30 kg/m2, inclusive. The minimum weight is 50 kg. 6. A female subject is eligible to participate in this study if she is of non-childbearing potential (defined as females with a documented tubal ligation, bilateral oophorectomy or hysterectomy) or postmenopausal (defined as 12 months of spontaneous amenorrhea and follicle stimulating hormone level within the laboratory's reference range for postmenopausal females). A post-menopausal female receiving hormone replacement therapy who is willing to discontinue hormone therapy 28 days before study drug dosing and agrees to remain off hormone replacement therapy for the duration of the study may be eligible for study participation. 7. If male, subject is surgically sterile or practicing required forms of birth control until 6 months after the last dose of the study drug(s). Males must agree to refrain from sperm donation from check-in through 6 months after the last dose of the study drug(s). 8. Subject has been a nonsmoker and has not used nicotine or nicotine-containing products for at least 6 months. 9. Subjects who participated in Part 1 and/or Part 2 may participate in subsequent Part(s) upon satisfactory completion of a posttreatment visit, 7 days (+2 days) following the subject's last dose, and provided they continue to meet all of the and none of the   Main Subject is mentally or legally incapacitated, has significant emotional problems at the time of prestudy (screening) visit or expected during the conduct of the study or has a history of a clinically significant psychiatric disorder over the last 5 to 10 years. 2. Subject has a history of any illness that, in the opinion of the investigator, would confound the objectives or results of the study or poses an additional risk to the subject by their participation in the study. 3. Subject has an estimated creatinine clearance of ≤80 mL/min based on the Cockcroft-Gault equation; An actual creatinine clearance, as determined by a 24-hour urine collection, may be used in place of, or in conjunction with, the Cockcroft-Gault equation; subjects who have an actual or estimated creatinine clearance within 10% of 80 mL/min may be enrolled in the study at the discretion of the investigator. 4. Pregnant or nursing (lactating) females, confirmed by a positive human chorionic gonadotropin laboratory test or females contemplating pregnancy. Men whose female partners are pregnant or contemplating pregnancy from the date of screening until 6 months after their last dose of study drugs. 5. Clinically significant cardiovascular, respiratory, skeletal, renal, gastrointestinal, hematologic, hepatic, immunological, neurologic, endocrine, genitourinary abnormalities or disease or any other medical illness as determined by the investigator or Sponsor's Medical Monitor. 6. Subject has a history of malignancy except completely excised basal cell carcinoma or squamous cell carcinoma of the skin. 7. Subject lacks or has poor peripheral venous access. 8. Positive screening result for hepatitis B, hepatitis C and/or HIV serology. 9. Any condition that, in the opinion of the investigator, would compromise the study's objectives or the well-being of the subject or prevent the subject from meeting the study requirements. 10. Clinically significant abnormal ECG findings. Particularly, a history or family history of prolonged QT syndrome (eg, torsade de pointes) or sudden cardiac death. 11. ECG with PR >200 ms, QRS >120 ms, QTcF >450 ms, as assessed by triplicate 12-lead ECG at the screening visit. 12. Subject has had major surgery, or clinically significant blood loss or elective blood donation of significant volume (ie, >500 mL) within 60 days of first dose of study drug; >1 unit of plasma within 7 days of first dose of study drug. 13. Abnormal heart rate, respiratory rate, temperature or blood pressure values outside of the normal range (evaluated in a semi-recumbent or recumbent position after 5 minutes of rest). One repeat measurement after an additional 5 minutes of rest is permitted. 14. Evidence of active infection. 15. Unwilling to abstain from alcohol for at least 48 hours prior to the start of dosing through the study completion visit. 16. History of regular alcohol intake >7 units per week of alcohol for females and >14 units per week for males (one unit is defined as 10 g alcohol) within 3 months of the screening visit. 17. The subject has a positive screening or Day -1 drugs of abuse screen. 18. The use of concomitant medications, including prescription, over the counter medications, and herbal medications (such as St. John's Wort [Hypericum perforatum]) within 30 days prior to the first dose of study medication is excluded, unless approved by the Sponsor's Medical Monitor. Occasional use of ibuprofen/paracetamol/ acetaminophen is permitted. 19. Subject has received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 90 days before the planned study drug. 20. Subject has a history of significant multiple and/or severe allergies, or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food. 21. Hypersensitivity to the active substances or to any of the excipients of AL-3778, entecavir or tenofovir disoproxil fumarate. 22. Subject has known allergy to heparin or history of heparin-induced thrombocytopenia. 23. Abnormal biochemistry or hematology laboratory results obtained at screening determined to be clinically significant by the Investigator. Screening ALT, AST, GGT, albumin, and total bilirubin must be within normal ranges. Creatine kinase >1.5 x ULN is exlusionary 24. Unwillingness or inability to comply with the study protocol for any other reason