Clinical Trial: De Novo Autoimmune Hepatitis in Pediatric Liver Transplantation

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: De Novo Autoimmune Hepatitis in Pediatric Liver Transplantation

Brief Summary: The purpose of this study is to provide insights into the cause, development and effects of de novo autoimmune hepatitis so that prevention and treatment strategies can be developed in order to reduce post-liver transplant morbidity, the frequency of liver allograft loss and the need for re-transplantation.

Detailed Summary:

This is a multi-site study with Yale University as the coordinating site. Our research plan is as follows:

Aim 1: To conduct a refined phenotypical and functional analysis of regulatory T cells in study and control patient groups.

Rationale: We would like to extend our preliminary data observations in a larger patient group and use this extended data set to conduct a refined phenotypical and functional analysis of regulatory T cells in order to explore if the regulatory T cell phenotype and function in d-AIH differs: (A) from that in controls defined as (i) non-transplanted patients with autoimmune hepatitis (AIH), (ii) LT recipients with acute rejection, (iii) LT recipients with chronic rejection, (iv) non-transplanted patients with chronic hepatitis C; (B) according to the disease etiology leading to transplantation; (C) according to immunosuppressive regimen prior to diagnosis of d-AIH being made and (D) over time during the disease course. This could potentially give us some insight into the causes for immune tolerance breakdown in d-AIH.

Aim 2: To investigate how over expression of IL-17A and HDAC9 genes relates to the regulatory T cell defect observed in liver transplant recipients with d-AIH.

Rationale: Histone/protein deacetylases regulate chromatin remodeling, gene expression and the functions of many transcription factors. Acetylation of histones leads to an open chromatin structure permissive for the initiation of gene transcription and expression. Histone deacetylase inhibition by Trichostatin-A (TSA) has been demonstrated to prevent the production of IL-17A and sustain Foxp3 expression in human T-regs. Importantly, if differentiation of T-regs into a Th17-like phenotype can be inhibited by TSA in d-AIH, this mig
Sponsor: Yale University

Current Primary Outcome:

• Liver Allograft Loss [ Time Frame: 3 years ]
  Assessment to determine the frequency of liver allograft loss.
• Need for Transplantation [ Time Frame: 3 years ]
  Assessment to determine the need for re-transplantation.

Original Primary Outcome:

• Liver Allograft Loss [ Time Frame: 3 years ]
  Assessment to determine the frequency of liver allograft loss.
• Need for Transportation [ Time Frame: 3 years ]
  Assessment to determine the need for re-transplantation.

Current Secondary Outcome:

Original Secondary Outcome:

Information By: Yale University

Dates:
Date Received: January 28, 2014
Date Started: March 2013
Date Completion: March 2017
Last Updated: July 11, 2016
Last Verified: July 2016