Transforming growth factor β1 polymorphisms and progression of graft fibrosis after liver transplantation for hepatitis C virus--induced liver disease

Liver Transpl. 2011 Mar;17(3):279-88. doi: 10.1002/lt.22190.

Abstract

Re-infection with the hepatitis C virus (HCV) is an important development after liver transplantation (LT); it can lead to graft fibrosis. The aim of this study was to assess the role of transforming growth factor β1 (TGF-β1) polymorphisms in the development of HCV-related graft disease by evaluating protocol liver biopsies. A total of 192 patients with a recurrence of HCV infection after LT were genotyped for TGF-β1 codon 10 (C→T) and codon 25 (G→C) using the polymerase chain reaction. Histological evaluation of 614 protocol liver biopsies obtained from these patients was undertaken using the classification of Desmet and Scheuer to stage the degree of fibrosis. Mild stages of fibrosis (0-2) were compared to advanced stages of fibrosis (3-4) that developed during the period of infection with the virus. Correlations between the prevalence of TGF-β1 genotypes and the different degrees of fibrosis that developed were determined. No statistically significant differences were found for genotype distributions (codons 10 and 25) with respect to recipient age, donor sex, occurrence of acute cellular rejection, and response to antiviral therapy. However, the C allele at codon 25 was significantly less frequent in the group with advanced fibrosis (P = 0.001). Furthermore, a positive association was found between progression of fibrosis and male recipient sex (P = 0.024), donor age (P = 0.041), and viral genotype 1b (P = 0.002). In conclusion, this study, in which the evolution of hepatic fibrosis was assessed histologically in a large cohort of patients with HCV re-infection after LT, has demonstrated that the C allele at codon 25 of the TGF-β1 gene is a marker for the development of graft fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents / therapeutic use
  • Biopsy
  • Chi-Square Distribution
  • Child
  • Codon
  • Disease Progression
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Germany
  • Graft Rejection / genetics
  • Graft Rejection / prevention & control
  • Graft Rejection / virology
  • Hepatitis C / diagnosis
  • Hepatitis C / drug therapy
  • Hepatitis C / genetics*
  • Humans
  • Liver Cirrhosis / genetics*
  • Liver Cirrhosis / pathology
  • Liver Cirrhosis / virology
  • Liver Transplantation / adverse effects*
  • Logistic Models
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Genetic*
  • Recurrence
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index
  • Time Factors
  • Transforming Growth Factor beta1 / genetics*
  • Treatment Outcome
  • Young Adult

Substances

  • Antiviral Agents
  • Codon
  • TGFB1 protein, human
  • Transforming Growth Factor beta1