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

A Multi-center, Randomized, Open Label, Controlled Study to Compare the Sustained Virological Response During Treatment With Neoral or Tacrolimus in Maintenance Liver Transplant Recipients Treated With Pegylated Interferon and Ribavirin for Recurrent Hepatitis C

This study will assess the rates of Sustained Virological Response following anti-viral therapy with Peg-Interferon plus Ribavirin in patients that have been liver transplanted with recurrent Hepatitis C and treated with Neoral or tacrolimus.

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