Genetic Variants of STAT-4 Affect the Development of Graft Fibrosisafter Liver Transplantation for HCV-Induced Liver Disease

Abstract

Background: HCV-re-infection after liver transplantation may lead to re-cirrhosis and seems to be influenced by genetic factors. 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: 160 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 (54.1) months (p=0.654), 65 (46.5%) patients developed advanced fibrosis. Advanced fibrosis was observed significantly more frequent in patients with at least one T-allele (n=64) compared to homozygotes (n=96) for G-allele (53.1% vs. 32.3%; p=0.013). Significant differences in the duration of advanced fibrosis development were detected between patients with at least one T-allele compared to 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). Conclusion: 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. T-allele seems to have a negative impact on fibrosis development and further risk factors should be investigated.