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

* 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 \<= 10 x the upper limit of normal (ULN)
  * AST \<= 10 x ULN
  * Total bilirubin \<2.5 mg/dL, Direct bilirubin \<= 1.5 ULN
  * Platelets \>= 50,000 K/mm\^3
  * HbA1c \<= 8.5%
  * Hemoglobin \>= 10g/dL
  * Albumin \>= 3g/dL
  * INR \<= 1.5 unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR.
  * HCV RNA positive at screening.
* Subjects must be of generally good health, with the exception of chronic HCV infection, as determined by the Investigator.

Phase II Follow-up

* Male or female \>= 18 years of age.
* SVR24 following therapy with a direct acting antiviral agent regimen and available liver biopsy performed prior to treatment.
* Subject must be of generally good health as determined by the Investigator.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

Phase I Treatment

* Pregnancy or lactation
* Inability to practice one form of adequate contraction for females of childbearing potential
* Prior treatment with a NS5a agent
* 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 \>= 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 \<5 years (except adequately treated carcinoma in situ or basal cell carcinoma of the skin).
* Chronic liver disease of a non-HCV etiology with the exception of steatosis (e.g., chronic hepatitis B, hemochromatosis, Wilson s disease, alfa-1 antitrypsin deficiency, cholangitis).
* Evidence of harmful or hazardous drinking as defined as a score \>= 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 \<5 years (except adequately treated carcinoma in situ or basal cell carcinoma of the skin)
  * Chronic liver disease with the exception of steatosis (e.g., chronic hepatitis B, hemochromatosis, Wilson s disease, alfa-1 antitrypsin deficiency, cholangitis)
  * Evidence of harmful or hazardous drinking as defined as a score \>= 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.