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): 18.0-80.0,  Chronic Hepatitis B HBeAg positive group 1. Age >18 years and older, male or female. 2. Known serum HBsAg and HBeAg positivity at the time of screening. 3. Ongoing treatment with one or more NUCs for at least 192 weeks before study entry. Subjects may have a brief interruption of treatment for medical reasons (e.g. breast feeding) not to exceed 8 weeks and none within the 48 weeks before study entry. 4. HBV DNA levels <100 IU/mL, measured at least 12 months prior to, and upon enrollment to the study. 5. ALT level less than or equal to 2 ULN based on at least two determinations taken at least one month apart during the 24 weeks before study entry with the second being at time of screening 6. Written informed consent HBeAg negative group 1. Age >18 years and older, male or female. 2. Known serum HBsAg positivity and HBeAg negativity at the time of screening. 3. Ongoing treatment with one or more NUCs for at least 192 weeks before study entry. Subjects may have a brief interruption of treatment for medical reasons (e.g. breast feeding) not to exceed 8 weeks and none within the 48 weeks before study entry. 4. HBV DNA levels <100 IU/mL, measured at least 12 months prior to, and upon enrollment to the study 5. ALT level less than or equal to 2 ULN based on at least two determinations taken at least one month apart during the 24 weeks before study entry with the second being at time of screening 6. Written informed consent  (for both eAg positive and negative patients) 1. Co-infection with HDV as defined by the presence of anti-HDV in serum and/or HDV antigen in the liver. 2. Co-infection with HCV as defined by the presence of HCV RNA in serum. 3. Co-infection with HIV as defined by the presence of anti-HIV in serum. 4. Decompensated liver disease as defined by serum bilirubin >2.5 mg/dL (with direct bilirubin > 0.5 mg/dL), prothrombin time of greater than 2 seconds prolonged, a serum albumin of less than 3 g/dL, or a history of ascites, variceal bleeding or hepatic encephalopathy. 5. Presence of other causes of liver disease, (i.e. hemochromatosis, Wilson disease, alcoholic liver disease, severe nonalcoholic steatohepatitis defined as the presence of marked ballooning injury on liver biopsy, alpha-1-anti-trypsin deficiency). 6. 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. 7. Significant systemic illness other than liver diseases including congestive heart failure, renal failure, chronic pancreatitis and diabetes mellitus with poor control, that in the opinion of the investigator may interfere with therapy. 8. Pregnancy or inability to practice contraception in patients capable of bearing or fathering children 9. Lactating women. 10. Hepatocellular carcinoma (HCC), or the presence of a mass on imaging studies of the liver that is suggestive of HCC, or an alpha-fetoprotein level of greater than 500 ng/mL. 11. eGFR < 50 ml/min, serum creatinine > 1.3 mg/dl or urine protein >1 gram/24-hours 12. History of hypersensitivity to pegylated interferon-alpha 13. Platelet count <70 mm(3)/dL 14. Hgb <12 g/dL for males and <11 g/dL for females 15. Active ethanol/drug abuse/psychiatric problems such as major depression, schizophrenia, bipolar illness, obsessive-compulsive disorder, severe anxiety, or personality disorder that, in the investigator s opinion, might interfere with participation in the study. 16. History of malignancy or treatment for a malignancy within the past 3 years (except adequately treated carcinoma in situ or basal cell carcinoma of the skin). 17. Any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids or other immunosuppressive medications during the course of this study. 18. History of immune-mediated disease, or cerebrovascular, chronic pulmonary or cardiac disease associated with functional limitation, retinopathy, uncontrolled thyroid disease, poorly controlled diabetes or uncontrolled seizure disorder, as determined by a study physician. 19. Presence of conditions that, in the opinion of the investigators, would not allow the patient to be followed in the current study for at 1 year. 20. For subjects who interrupt therapy, documentation of a viral load >1,000 IU/ml while off therapy