title: Genetic variants of STAT-4 affect the development of graft fibrosis after liver transplantation for HCV-induced liver disease.
abstract: BACKGROUND
  Hepatitis C virus (HCV) reinfection after liver transplantation may lead to recirrhosis and seems to be influenced by genetic factors. The aim of our study was to evaluate the role of STAT-4-polymorphisms in the development of HCV-related graft disease based on protocol biopsies.
  
  
  METHODS
  One hundred sixty transplant patients with HCV recurrence were genotyped for STAT-4 (rs7574865) by polymerase chain reaction. Fibrosis stages were determined based on Desmet and Scheuer classification. SPSS was used for the statistical analysis of genotype distribution and of time to the development of advanced fibrosis among the genotypes.
  
  
  RESULTS
  During a comparable observation period of 86.2 months (P=0.654), 65 patients (46.5%) developed advanced fibrosis. Advanced fibrosis was observed significantly more frequent in patients (n=34) with at least one T-allele (53.1 vs. 32.3%; P=0.013) compared with homozygotes for G-allele (n=31). Significant differences in the duration of advanced fibrosis development were detected between patients with at least one T-allele compared with G-allele (34.4 vs. 49.0 months; P=0.022). No impact was observed regarding the outcome of interferon-based antiviral treatment (P=0.297) and the occurrence of acute cellular rejection (P=0.365).
  
  
  CONCLUSIONS
  Present results indicate a possible impact of genetic confounders in the recipient on graft fibrogenesis, thus explaining significantly different graft behavior observed after transplantation for HCV-associated liver disease. STAT-4-T-allele is identified as fibrogenic factor and seems to have a negative impact on HCV-induced fibrosis development.
authors.affiliation: Charité Campus Virchow, Department of General, Visceral and Transplantation Surgery, Berlin, Germany. dennis.eurich@charite.de
authors.forename: Dennis
authors.initials: D
authors.lastname: Eurich
authors.forename: Sabine
authors.initials: S
authors.lastname: Boas-Knoop
authors.forename: Benjamin
authors.initials: B
authors.lastname: Struecker
authors.forename: Ruth
authors.initials: R
authors.lastname: Neuhaus
authors.forename: Peter
authors.initials: P
authors.lastname: Neuhaus
authors.forename: Marcus
authors.initials: M
authors.lastname: Bahra
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006526:Hepatitis C / Q000235:genetics / Q000601:surgery*; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology / Q000235:genetics*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D050797:STAT4 Transcription Factor / Q000235:genetics*
chemical_list: D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human