Response Guided Treatment With Direct Acting Anti-Viral Medications for Chronic HCV Infection
Response Guided Treatment With Direct Acting Anti-Viral Medications for Chronic HCV Infection
To evaluate the efficacy and safety of direct acting anti-viral agents (DAA) therapy in
 chronically infected Hepatitis C Virus (HCV) patients using an individualized response guided
 therapy (RGT) model.
Treatment of HCV infection is directed at achieving sustained virological response (SVR),
 defined as the continued absence of detectable HCV RNA for 12 or more weeks after completion
 of therapy Given the limited resources available for the costly DAA treatment, implementation
 of a response-guided treatment (RGT) model to individualize length of DAA therapy in a
 prospective setting could result in substantial cost saving on HCV drug expenditure in
 addition to improving patients' compliance to treatment. Furthermore, if adopted at a larger
 scale, incorporation of such model into clinical practice may enable expansion of access to
 DAA therapy for patients who are currently not included in the various treatment programs,
 especially in resource-limited countries.
Inclusion Criteria:

 1. Signed informed consent

 2. Clalit insured patients

 3. Female and male over the age of 18

 4. Capacity to provide written informed consent

 5. HCV RNA Viral Load (VL) larger than 105 IU/mL at screening and on at least one other
 occasion 6 months or more prior to the most recent HCV RNA test result.

 6. HCV genotypes 1a, 1b, 2, 3 or 4

 7. Liver fibrosis stage 0-4 as determined by one of the following methods performed
 within 2 years prior to the screening visit:

 1. Fibrotest

 2. Transient elastography

 3. Liver biopsy using the METAVIR scoring system.

 8. Patients must have the following laboratory parameters within 3 months of screening

 1. ALT and AST ≤ x10 the upper limit of normal (ULN)

 2. Direct bilirubin ≤ 1.5 the ULN

 3. Platelet count ≥70,000

 4. Hemoglobin ≥10 mg/dL

 5. Albumin ≥3 mg/dL

 6. INR ≤ 1.5 x ULN

 7. eGFR ≥ 60 mL/min as calculated by the Cockroft-Gault equation.

 9. Abdominal ultrasound, C.T or MRI scan showing no evidence of a focal lesion suspicious
 of hepatocellular carcinoma within 6 months of enrollment.

 10. A female patient will be eligible to enter the study if it is confirmed that she is:

 1. Not pregnant or nursing

 2. Of non-childbearing potential (following hysterectomy, bilateral oophorectomy or
 post-menopausal)

 3. Women of childbearing potential- must have a negative urine pregnancy test at
 baseline and willing to use an accepted mechanical, medical or surgical birth
 control method from the day of screening until 90 days from the last dose of
 study drug.

 11. All male participants in the study must agree to consistently and correctly use a
 condom, while their female partner agrees to use one of the above-mentioned birth
 control methods from the day of screening until 90 days after the last dose of study
 drug.

 12. Patient must be able to comply with the dosing instructions for the study drug
 administration and able to complete the study schedule of assessments including all
 required post-treatment visits.

 Exclusion Criteria:

 1. Clinical, serologic or histopathological evidence supporting the presence of chronic
 liver disease other than HCV (Including but not limited to: HBV, HDV or HIV
 coinfection, non-alcoholic steatohepatitis, alcoholic liver disease, Wilson's disease,
 A1AT deficiency and Celiac disease). Workup performed within 6 months of recruitment
 will be considered sufficient to exclude the above-mentioned conditions (except for
 A1AT deficiency and Wilson's disease for which exclusion at any time point qualifies).

 2. Current or past history of any of the following:

 1. Clinically significant illness (other than HCV) or any other medical disorder
 that may interfere with patient's assessment, treatment or compliance with the
 protocol. Examples include congestive heart disease with moderate to severe left
 ventricular function and chronic obstructive pulmonary disease requiring chronic
 corticosteroid therapy.

 2. Clinical evidence of decompensated liver disease (e.g. ascites, bleeding
 esophageal varices, spontaneous bacterial peritonitis, encephalopathy or
 hepatorenal syndrome.)

 3. Child Pugh score higher than 6

 4. Gastrointestinal disorder or post-operative condition that may interfere with the
 absorption of the study drug.

 5. Solid organ transplantation

 6. Malignancy within 5 years prior to screening with the exception of specific
 cancers that are entirely cured by surgical resection (basal cell skin cancer
 etc.) Patients under the evaluation for possible malignancy are not eligible.

 3. Any prior treatment with a DAA (protease inhibitors, NS5A inhibitors, NS5B polymerase
 inhibitors/non-nucleoside polymerase inhibitors)

 4. Use of anti-viral medications within 30 days of screening.

 5. Chronic use of systemically administered immunosuppressive/immune- modulating
 medications

 6. Clinically relevant substance abuse within 6 months of enrollment. Patient with prior
 history of drug addiction who are currently maintained on a stable dose of opiate
 substitutes (naloxone) will be allowed to participate in the study if they can provide
 documentation of repeated negative toxicology screens from the 6 months prior to
 screening.

 7. Participating in clinical trial 30 days before screening.