The Potential Association of Apolipoprotein E and Interleukin-28B Genetic Variants with Hepatitis C Virus Recurrence Following Liver Transplantation

Abstract

HCV recurrence represents a universal phenomenon after liver transplantation. Many genes and their single nucleotide polymorphisms (SNPs) are associated with the recurrence of HCV infection after liver transplantation. An increasing cause of mortality in Egypt in the last decade is end stage liver disease (ESLD) secondary to HCV infection. The purpose of the present study was analyzing the co-prevalence of three common and clinically significant SNPs in a cohort of Egyptian subjects (donor and/or recipient) on the frequency of HCV recurrence and its association with survival rate after transplantation. Three SNPs were genotyped (two loci (rs12979860, rs8099917) in IL-28 and one in apolipoprotein E3 in 100 DNA samples collected from HCV-infected patients using TaqMan allelic discrimination assay and PCR-RFLP, respectively. HCV-RNA levels were determined before transplantation and 24 months later by quantitative real-time polymerase chain reaction (qPCR). The overall genotype distributions of IL-28B rs12979860 CC, -CT, and -TT were 45, 33, and 22%, respectively, and the distributions of rs8099917 TT, -TG, and -GG were 71, 25, and 4%, respectively. In recipients, the genotype distributions of ApoE were 89% and 11% for E3E3 and E3E4, respectively. In donors, ApoE E3E3 and E3E4 genotype distributions were 91% and 9%, respectively. Recipients with the favorable IL-28 rs12979860 homozygous allele (CC) had a higher rate of SVR than those with the heterozygous allele. Recipients with the favorable IL-28 rs8099917 allele (TT) had a higher rate of SVR than those with the heterozygous allele. Regarding ApoE, different genotypes between donors and recipients were associated with a higher rate of SVR than those with the same genotype (P= 0.013). In conclusion, it might be useful to combine the IL28B genotype with other associated markers, to further increase the predictive era of the polymorphism. Furthermore, we hope that ApoE genotyping may be a helpful element to support clinical decision-making in HCV patients. ApoE genotyping might prove to be a precious point to take into consideration during antiviral treatment of recurrent HCV infection