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