People With CHC Who Achieved a Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents

Background: Chronic hepatitis C infects the liver. It may scar the liver. This is called cirrhosis and may lead to liver cancer or death. Current chronic hepatitis C treatments cure most people. But some keep getting complications even after it is cured. Researchers want to study why. Objective: To study the course and complications of liver disease after cure of hepatitis C infection. Eligibility: Adults 18 years and older infected with chronic hepatitis C virus who were never treated or were treated and not cured and those who were cured Design: Participants will be screened with: Blood and urine tests Questionnaires Liver ultrasound Fibroscan. A probe vibrates the liver, testing stiffness. In Phase 1, people with chronic hepatitis C will: Have a 3-day hospital admission to repeat some screening tests and have a liver biopsy. A small piece of liver is removed by needle passed through the skin. Take 1 tablet containing 2 hepatitis C drugs once a day for 12 weeks. Repeat some blood tests at 3 visits in those 12 weeks while on treatment, then 4 additional visits in the next 24 weeks with more blood work collected. Phase 1 participants who test negative for hepatitis C and all other eligible participants will enter Phase 2. Phase 2 participants will have a visit every 24 weeks for 10 years. These may include: Repeats of screening tests Questionnaires Scans Stool tests Chest x-ray Heart function test Endoscopy. A tube guides a camera into the upper digestive system. At about 5 years, participants will have another liver biopsy. Some participants will give separate consent for genetic testing and a special blood procedure.

* INCLUSION CRITERIA: Phase I Treatment * Male or female \>= 18 years of age * Either treatment naive or experienced defined as failure of a prior course of interferon-based and ribavirin, DAA plus interferon and DAA only * Confirmation of chronic HCV infection documented by: * A positive HCV RNA or positive HCV genotyping test at least 6-months prior to the Baseline/Day 1 visit * A liver biopsy performed prior to screening visit showing evidence of chronic hepatitis. * Subjects must have the following laboratory parameters at screening: * ALT \= 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 * History of malignancy or treatment for a malignancy within the past 3 years that is associated with a life expectancy \= 8 on the AUDIT questionnaire. * Co-infection with HIV defined as the presence of anti-HIV in serum. * Clinically relevant drug abuse based on patient history within 12 months of screening. * Use of medications contraindicated with use of sofosbuvir/velpatasvir within 21 days of the Baseline/Day 1 visit; this washout period does not apply to proton pump inhibitors, which can be taken up to 7 days before baseline Day 1 for the following: * Acid reducing Agents * Antiarrhythmics * Anticancer * Antimycobacterial * HIV antivirals * Herbal supplements * HMG-CoA Reductase Inhibitors * Use of antiviral medications within the last 30 days. * Chronic use of systemically administered immunosuppressive agents (e.g., prednisone equivalent \>= 10 mg/day). * Known hypersensitivity to sofosbuvir and velpatasvir, or formulation excipients. * Hepatocellular carcinoma, or the presence of a mass on imaging studies of the liver that is suggestive of hepatocellular carcinoma, or an alpha-fetoprotein level of greater than 500 mg/mL * 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. * Presence of conditions that, in the opinion of the investigators, would not allow the subject to n the current study for at least 1 year. Phase II Follow-up * Pregnancy * 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 \>= 2.5 mg/dL (with direct bilirubin \>= 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 * History of malignancy or treatment for a malignancy within the past 3 years that is associated with a life expectancy \= 8 on the AUDIT questionnaire * Co-infection with HIV defined as the presence of anti-HIV in serum * Clinically relevant drug abuse based on patient history within 12 months of screening * Chronic use of systemically administered immunosuppressive agents (e.g., prednisone equivalent \>= 10 mg/day) * Hepatocellular carcinoma, or the presence of a mass on imaging studies of the liver that is suggestive of hepatocellular carcinoma, or an alpha-fetoprotein level of greater than 500 mg/mL * 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 * 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.