the Effect of Grazoprevir/Elbasvir and TACE vs. TACE Alone in Prolonging Survival of Patients With Non-resectable HCV Associated HCC.

Single center, open label, prospective pilot study. The study will include 20 HCV genotype 1 (a and b) cirrhotic patients (Child Pugh A compensated cirrhosis) with advanced, un-resectable HCC who are eligible for TACE. This pilot study will have one arm which will be compared to historical controls. All patients participating in the study will receive Grazoprevir/Elbasvir treatment according to established guidelines together with regular TACE treatments. The historical controls will refer to patients who received regular TACE treatments alone (standard of HCC care). Follow up will be for up to 24 months from TACE initiation.

• Grazoprevir/Elbasvir (Drug): anti-viral treatment for HCV
• Medical records (Other): Medical records of patients who underwent Transarterial Chemoembolization only, in the past.
• Transarterial Chemoembolization (Procedure): A minimally invasive procedure performed in interventional radiology to restrict a tumor's blood supply. Small embolic particles coated with chemotherapeutic drugs are injected selectively through a catheter into an artery directly supplying the tumor. These particles both block the blood supply and induce cytotoxicity, attacking the tumor in several ways.

Primary outcomes

• Overall survival [assessed up to 24 months]: 15% or more increase in survival with the combination treatment of Grazoprevir/Elbasvir and TACE vs. historical control of TACE alone; Time Frame: from start of treatment to death from any cause, or last known date of survival
• Adverse events and serious adverse events (AEs, SAEs) [24 months]: will be assessed in all patients receiving at least one dose of a combination therapy, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
• Time to progression (TTP) [Assessed, up to 24 months]: Time from start of treatment until the first documented event of symptomatic progression.
• SVR12 rates [12 weeks after the last actual dose of Grazoprevir/Elbasvir]: : proportion of patients achieving SVR12
• Hepatic de-compensation as assessed by clinical end-points [Once a month up to 24 months]: development of ascites, and will undergo repeated liver function tests every 2 weeks to detect CPT increase.

Secondary outcomes

• Time to radiologic progression [The time from start of treatment to disease progression, according to mRECIST, assessed up to 24 months.]: a decrease in tumor in 15 % or more of the patients undergoing combination therapy vs. historical control of TACE alone
• Disease-control rate [at least 28 days after the first demonstration of that rating on the basis of independent radiologic review]: The percentage of patients who had a best-response rating of complete response, partial response, or stable disease (according to mRECIST) that was maintained for at least 28 days after the first demonstration of that rating on the basis of independent radiologic review
• decrease in tumor markers [Screening and 24 months.]: A 50 % decrease in tumor markers in 15 % or more patients undergoing combination therapy vs. TACE alone
• quality of life [At screening, and months 3,13,22.]: Assess quality of life as measured by SF-36 questionnaire
• Symptom severity score [At screening, and months 3,13,22.]: Assess severity of symptoms as measured by FSHI8 questionnaire

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

1. Patients with chronic HCV genotype 1 (a and b) infection and un-resectable HCC who are eligible for TACE
2. Ages 18-75 years
3. Willing to take part in a clinical trial and have signed an informed consent
4. Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less
5. Child-Pugh liver function class A
6. Patients with expected survival of less than 1 year
7. Adequate hematologic function (plt≥60, 000 /L; Hb≥8.5 g/dl; and INR≤1.7
8. Adequate hepatic function (albumin ≥3.5 g/dl; total bilirubin, ≤2 mg/dl; ALT and AST ≤5 times the upper limit of the normal range)
9. Adequate renal function (serum creatinine ≤1.5 times the upper limit of normal range).

Exclusion Criteria:

1. Patients unwilling to sign the informed consent
2. Patients unwilling or not capable to complete the anti-viral treatment with Grazoprevir/Elbasvir
3. CPT score >7
4. Patients ineligible for TACE
5. Patients with contraindications to elbasvir/grazoprevir
6. Patients suffering from other underlying liver disease (HBV, HIV, PSC, PBC, AIH etc.)
7. Patients with malignancies other than HCC
8. Patients with previous anti-HCC treatment (RFA, TACE, SIRT or sorafenib)
9. Active alcohol or substance use
10. Previous liver transplantations
11. Child Pugh B or C cirrhosis
12. Total serum bilirubin >1.9 mg/dL
13. Extra-hepatic spread (metastases)
14. Pregnant/lactating women, minors and disabled/incapacitated persons