الفهرس | Only 14 pages are availabe for public view |
Abstract Liver disease caused by the hepatitis C virus (HCV) is the main indication for liver transplantation in Western countries. The highest prevalence of hepatitis c infection is in Egypt over the world, averaging 15-25% in rural communities, with >90% having HCV genotype 4. Furthermore, reports indicate that HCV genotype 4 is starting to unfold from its native African and geographical region origins to countries of Southern Europe and in some foci in the USA. Egyptian population has a heavy burden of liver disease, mostly due to chronic infection with HCV. An increasing cause of mortality in Egypt in the last decade is End stage liver disease (ESLD) secondary to HCV infection. HCV recurrence represents a universal phenomenon after liver transplantation and HCV RNA concentration increases progressively as early as 12h after graft reperfusion. The spontaneous clearance of HCV infection after transplant is very rare. It has been reported that the main indication for liver transplantation is HCVrelated ESLD and represents 89.8% of cases in Egypt. Because of the impact of HCV recurrence on graft and patient survival, many treatment ways are updated. Early with living donor liver transplantation (LDLT) in the setting of chronic HCV infection suggested a less successful outcome than from deceased donors. Liver transplantation (LT) provides a novel chance to analyze the contribution of the liver to the synthesis and degradation of genetically polymorphic plasma proteins. In humans, 3 major co-dominant alleles (E2, E3, E4) for a single gene locus coded ApoE. A change that causes profound functional consequences at both the cellular and molecular levels. Genome-wide association studies have shown that SNPs in or near the interleukin-28B (IL-28B) gene are significantly associated with the treatment outcome for HCV-infected patients. The aim of the present study is to evaluate the potential association of Apolipoprotein E and Interleukin- 28B single nucleotide polymorphisms (SNPs) in donors and/or recipients with HCV recurrence following liver transplantation. Three SNPs were genotyped (two loci [rs12979860 and rs8099917]) in IL-28 and one in apolipoprotein E3 in 100 DNA samples collected from HCV-infected patients using TaqMan Allelic Discrimination assay and PCRRFLP, respectively. HCV-RNA levels were determined before transplantation and 24 months later by quantitative real-time polymerase chain reaction (qPCR). Recipients who had the favorable IL-28 rs12979860 homozygous allele (CC) had a higher rate of SVR than those with the heterozygous allele. Recipients who had the favorable IL-28 rs8099917 homozygous allele (TT) had a higher rate of SVR than those with the heterozygous allele. Regarding ApoE, different ApoE genotypes between donors and recipients were associated with a higher rate of SVR than those with the same genotype. In conclusion, to improve prediction of HCV recurrence, different clinical and genomic data have been combined in logistic models. The simultaneous determination of two IL28B SNPs could be useful in some HCV infected patients to guide therapeutic decisions and improve treatment management and should therefore be included in the panel of pre-treatment evaluations. Furthermore, we hope that ApoE genotyping may be a helpful element to support clinical decision-making in these patients. If these results were confirmed in a wider series, ApoE genotyping might prove to be a precious point to take into consideration during antiviral treatment of recurrent HCV infection. |