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 ofinterferon-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 tothe Baseline/Day 1 visit

• A liver biopsy performed prior to screening visit showing evidence of chronichepatitis.

• 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 anticoagulantregimen affecting INR.

• HCV RNA positive at screening.

• Subjects must be of generally good health, with the exception of chronic HCVinfection, 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 availableliver 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 childbearingpotential

• 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 medicaldisorder that may interfere with subject treatment, assessment, or compliancewith the protocol; subjects currently under evaluation for a potentiallyclinically significant illness (other than HCV) are also excluded

• Gastrointestinal disorder or post-operative condition that could interfere withthe absorption of the study drug

• Decompensated liver disease as defined by serum bilirubin >= 2.5 mg/dL (withdirect 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 hepaticencephalopathy

• Solid organ transplantation

• Significant pulmonary disease, significant cardiac disease

• History of malignancy or treatment for a malignancy within the past 3 years that isassociated with a life expectancy <5 years (except adequately treated carcinoma insitu 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 antitrypsindeficiency, cholangitis).

• Evidence of harmful or hazardous drinking as defined as a score >= 8 on the AUDITquestionnaire.

• Co-infection with HIV defined as the presence of anti-HIV in serum.

• Clinically relevant drug abuse based on patient history within 12 months ofscreening.

• Use of medications contraindicated with use of sofosbuvir/velpatasvir within 21 daysof the Baseline/Day 1 visit; this washout period does not apply to proton pumpinhibitors, 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., prednisoneequivalent >= 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 liverthat is suggestive of hepatocellular carcinoma, or an alpha-fetoprotein level ofgreater than 500 mg/mL

• Active psychiatric problems such as major depression, schizophrenia, bipolarillness, obsessive-compulsive disorder, severe anxiety, or personality disorderthat, in the investigator s opinion, might interfere with participation in thestudy.

• Presence of conditions that, in the opinion of the investigators, would not allowthe 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 majormedical disorder that may interfere with subject treatment, assessment, orcompliance with the protocol; subjects currently under evaluation for apotentially 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 yearsthat is associated with a life expectancy <5 years (except adequately treatedcarcinoma in situ or basal cell carcinoma of the skin)

• Chronic liver disease with the exception of steatosis (e.g., chronic hepatitisB, hemochromatosis, Wilson s disease, alfa-1 antitrypsin deficiency,cholangitis)

• Evidence of harmful or hazardous drinking as defined as a score >= 8 on theAUDIT 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 ofscreening

• 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 theliver that is suggestive of hepatocellular carcinoma, or an alpha-fetoproteinlevel of greater than 500 mg/mL

• Active psychiatric problems such as major depression, schizophrenia, bipolarillness, obsessive-compulsive disorder, severe anxiety, or personality disorderthat, in the investigator s opinion, might interfere with participation in thestudy

• Presence of conditions that, in the opinion of the investigators, would notallow the patient to be followed in the current study for at least 1 year.