Sustained Virological Response (SVR) to Antiviral Treatment of Liver Transplant Recipients With Recurrent Hepatitis C

Inclusion criteria:

   - Liver transplantation performed at least 6 months and up to 5 years prior
   randomization and due to HCV cirrhosis, with or without pre-transplant hepatocellular
   carcinoma (HCC) within Milan or UCSF criteria

   - Immunosuppresive regimen based on tacrolimus b.i.d.- (twice or once daily) for at
   least 6 months prior randomization

   - Diagnosis of HCV genotypes 1 or 4 infection prior to transplantationconfirmed at
   screening

   - Indication of treatment with Peg-IFN and ribavirin due to histological evidence of
   chronic HCV infection defined as a fibrosis stage equal or greater than 1 using the
   Ishak-Knodell scoring system (IK ≥1) in a liver biopsy performed at screening or up to
   4 months prior to randomization.

Exclusion criteria:

   - Serum creatinine >150 μmol/L (1.6 7 mg/dL) or eGFR < 50 ml/min (4-variable
   Modification of Diet in Renal Disease [MDRD Cockcroft-Gault formula])

   - Multi-organ transplant recipients

   - Recent episode of steroid-treated acute rejection (AR) within 3 months prior to
   randomization, or >1 episode of steroid-treated AR in the last 6 months, or any number
   of steroid-resistant AR episodes in the last 6 months including evidence of chronic
   rejection or ductopenia

   - Evidence of conditions that could cause graft dysfunction other than HCV infection

   - Patients with signs of decompensated liver disease, defined as presence of ascites,
   variceal bleeding, encephalopathy or deteriorated hepatic synthetic function (albumin
   <3.5g/dL or, total direct bilirubin >1.5mg/dL or, INR >1.5)

   - Co-infection with HIV or Hepatitis B (defined as HBsAg-positive) at screening

   - Use of mTOR inhibitors (everolimus or sirolimus) in the 6 months prior to screening

   - Antiviral treatment for HCV administered at any time after liver transplantation

   - Patients on daily doses of corticosteroids higher than 5 mg/day

   - Patients with fibrosing cholestatic hepatitis

   - Patients with current diagnosis of malignancies, including lymphoproliferative
   disorders

   - Patients with platelet count <70,000/mm3 or neutrophiles <1,500/mm3

   - History of HCC outside Milan criteria based on radiology or UCSF criteria based on
   analysis of the explant