Transforming growth factor β1 polymorphisms and progression of graft fibrosis after liver transplantation for hepatitis C virus--induced liver disease
Open Access
- 21 September 2010
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Liver Transplantation
- Vol. 17 (3), 279-288
- https://doi.org/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. Liver Transpl, 2011. © 2011 AASLD.Keywords
This publication has 45 references indexed in Scilit:
- Hepatic stellate cell activation in liver transplant patients with hepatitis C recurrence and in non-transplanted patients with chronic hepatitis CLiver Transplantation, 2007
- TGF-β1 gene polymorphism in liver graft recipientsTransplant Immunology, 2006
- Fibrosis progression after liver transplantation in patients with recurrent hepatitis CJournal of Hepatology, 2004
- Impact of immunosuppressive therapy on recurrence of hepatitis CLiver Transplantation, 2002
- Chronic liver injury, TGF-β, and cancerExperimental & Molecular Medicine, 2001
- Molecular and functional aspects of latent transforming growth factor-β binding protein: just a masking protein?Cell and tissue research, 1999
- TGF-?? QUANTITATION CAN BE TRICKYTransplantation, 1999
- CA repeat allele polymorphism in the first intron of the human interferon-γ gene is associated with lung allograft fibrosisHuman Immunology, 1999
- Intra-observer variation in the histopathological assessment of chronic viral hepatitisJournal of Hepatology, 1996
- Transforming Growth Factors β1 and α in Chronic Liver DiseaseThe New England Journal of Medicine, 1991