Patient description: The patient is a 55-year-old man diagnosed with HCV 2 years ago and the recent coinfection with HBV. His past medical history is non-significant. He is on IFN, RBV and direct antiviral drugs for the past 6 months. The patient takes no other medications. His medical records show previous positive HCV RNA tests and a 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): 18.0-90.0,  Diabetes Mellitus Hepatitis C, Chronic Cardiovascular Diseases Phase I for Subjects Who Have Not Achieved a SVR (Phase I) Subjects must meet all of the following to be eligible for participation in this study: 1. Male or female, age greater than or equal to 18 years. 2. Either treatment na(SqrRoot) ve or experienced defined as failure of a prior course of interferon-based and ribavirin, DAA plus interferon and DAA only (except for NS5a failures). 3. Confirmation of chronic HCV infection documented by either: 1. A positive HCV RNA or positive HCV genotyping test at least 6 months prior to the Baseline/Day 1 visit, or 2. A liver biopsy performed prior to screening visit showing evidence of chronic hepatitis. 4. Subjects must have the following laboratory parameters at screening ALT less than or equal to 10 (SqrRoot) the upper limit of normal (ULN) AST less than or equal 10 (SqrRoot) ULN Total bilirubin <2.5 mg/dL, Direct bilirubin less than or equal 1.5 ULN Platelets more than or equal 50,000 K/mm3 HbA1c less than or equal 8.5% eGFR more than or equal 60 mL /min, as calculated by the CKD-EPI equation Hemoglobin more than or equal 10g/dL Albumin more than or equal 3g/dL INR less than or equal 1.5 unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR  for Subjects Who Have Not Achieved a SVR Subjects who meet any of the following will not to be enrolled in this arm of the study: 1. Pregnancy, active breast-feeding, or inability to practice adequate contraception, in women of childbearing potential. Adequate contraception is defined as vasectomy in men, tubal ligation in women, or use of one method such as condoms and spermicide combination, birth control pills, an intrauterine device, Depo-Provera, or Norplant until 12 weeks post therapy. 2. Current or prior history of any of the following Clinically-significant illness (other than HCV) or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol; subjects currently under evaluation for a potentially clinically-significant illness (other than HCV) are also excluded Gastrointestinal disorder or post-operative condition that could interfere with the absorption of the study drug Decompensated liver disease as defined by serum bilirubin more than or equal to 2.5 mg/dL (with direct bilirubin more than or equal to 1.5 mg/dL), INR >1.5 a serum albumin of less than 3 g/dL, or a history of ascites, hepatorenal syndrome, variceal bleeding or hepatic encephalopathy Solid organ transplantation Significant pulmonary disease, significant cardiac disease or porphyria. 3. History of malignancy or treatment for a malignancy within the past 3 years that is associated with a life expectancy <5 years (except adequately treated carcinoma in situ or basal cell carcinoma of the skin). 4. Chronic liver disease of a non-HCV etiology with the exception of steatosis (e.g., chronic hepatitis B, NASH, hemochromatosis, Wilson s disease, alfa-1 antitrypsin deficiency, cholangitis). 5. Evidence of harmful or hazardous drinking as defined as a score more than or equal to 8 on the AUDIT questionnaire. 6. Co-infection with HIV defined as the presence of anti-HIV in serum. 7. Clinically-relevant drug abuse based on patient history within 12 months of screening. 8. Use of any prohibited concomitant medications as described in concomitant medications and Table 1 within 21 days of the Baseline/Day 1 visit; this washout period does not apply to PPIs, which can be taken up to 7 days before baseline Day 1. 9. Use of antiviral medications within the last 30 days. 10. Chronic use of systemically administered immunosuppressive agents (e.g., prednisone equivalent more than or equal to 10 mg/day). 11. Known hypersensitivity to sofosbuvir and velpatasvir, or formulation excipients. 12. Hepatocellular carcinoma, or the presence of a mass on imaging studies of the liver that is suggestive of hepatocellular carcinoma, or an alphafetoprotein level of greater than 500 ng/mL. 13. Active 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. 14. Presence of conditions that, in the opinion of the investigators, would not allow the patient to be followed in the current study for at least 1 year. 15. Inability to provide consent. Phase II for Phase II (follow-up after SVR24): 1. Age greater than or equal to 18 years and older, male or female 2. SVR following therapy with a direct acting antiviral agent regimen and available liver biopsy performed prior to treatment 3. Subject must be of generally good health as determined by the Investigator for Phase II (follow-up after SVR24): 1. Current or prior history of any of the following Clinically-significant illness (other than resolved HCV) or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol; subjects currently under evaluation for a potentially clinically-significant illness (other than HCV) are also excluded Decompensated liver disease as defined by serum bilirubin greater than or equal to 2.5 mg/dL (with direct bilirubin greater than or equal to 1.5 mg/dL), INR >1.5 a serum albumin of less than 3 g/dL, or a history of ascites, hepatorenal syndrome, variceal bleeding or hepatic encephalopathy