The Impact of Everolimus Based Immunosuppression in the Evolution of Hepatitis C Fibrosis After Liver Transplantation

Summary

Background:

Hepatitis C recurrence, which invariably occurs in viremic liver transplant (LT) recipients, associated with accelerated liver fibrosis leading to established graft cirrhosis in 40-20% of patients in 5 years with another 5% experiencing an aggressive form with cirrhosis and graft loss in 1 year. Since treatment after LT has a low efficacy, the overall survival of HCV-infected LT recipients is shorter than that of uninfected LT patients.

New immunosuppressive agents such as mTOR inhibitors (Everolimus/Sirolimus) reduce the risk of liver graft rejection, have antifibrotic properties and do not worsen HCV recurrence. Moreover new directly-acting antiviral agents have increased efficacy of interferon-based treatment but their use in LT recipients may be limited by side effects.

Hypothesis:

Use of individualized immunosuppressive regimen and early personalized anti-viral treatment based on recipient and viral factors would improve outcome of HCV infected liver transplant recipients.

Objectives:

1. To evaluate safety and efficacy of two steroid-free immunosuppressive regimens to reduce hepatitis C recurrence associated to fibrosis progression (F≥2 under ISHAK score) at one year post-transplant.
2. To identify viral and recipient factors associated with liver fibrosis progression using ultra-deep pyrosequencing (UDPS).

Conditions

• Hepatitis C Recurrence After Liver Transplant

Interventions

DRUG

EVL arm

Patients will be randomized at day 28th post-transplant. This group will receive Tacrolimus+Everolimus.

DRUG

MMF arm

Patients will be randomized at day 28th post-transplant. This group will continue of current immunosuppressive regimen (Tacrolimus+MMF) / no everolimus introduction.

Sponsors & Collaborators

• Hospital Vall d'Hebron

  lead OTHER

Principal Investigators

• Itxarone Bilbao, PhD/MD · Department of HPB Surgery and Transplant, Hospital Vall d´Hebron (Barcelona, Spain)

• Ramon Charco, PhD/MD · Department of HPB and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)

• Josep Quer, PhD/MD · Hepatology Unit, Department of Internal Medicine, Hospital Vall d´Hebron, CIBERehd, Barcelona (Spain)

• Francisco Rodríguez, PhD/MD · Biochemistry Laboratory, Hospital Vall d´Hebron, Barcelona (Spain)

• Gonzalo Sapisochin, PhD/MD · Department of HPB Surgery and Transplant, Hospital Vall d´Hebron, Barcelona (Spain)

• Lluis Castells, PhD/MD · Hepatology Unit, Department of Internal Medicine, Hospital Vall d´Hebron, CIBERehd, Barcelona (Spain)

• Isabel Campos, PhD · Hepatology Unit, Department of Internal Medicine, Hospital Vall d´Hebron, CIBERehd, Barcelona (Spain)

• Helena Allende, PhD/MD · Department of Anatomo-Pathology, Hospital Vall d´Hebron, Barcelona (Spain)

• Jose Luis Lazaro, PhD · Department of HPB surgery and Transplant, Hospital Vall d´Hebron, Barcelona (Spain)

• Cristina Dopazo-Taboada, PhD/MD · Department of HPB and Transplant, Hospital Vall d´Hebron, Barcelona (Spain)

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

68 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-10-31

Primary Completion

2016-08-31

Completion

2016-08-31

Countries

• Spain

Study Locations