Search In this Thesis
   Search In this Thesis  
العنوان
Role of toll like receptor polymorphism in the outcome of liver transplantation for chronic hepatitis C virus /
المؤلف
Helal, Ghada Mohamad Moneir.
هيئة الاعداد
باحث / غاده محمد منير هلال
مشرف / /محمد محمد علي سعيد
مشرف / محمد عبدالوهاب علي
مشرف / فجر بكر بازيد
مشرف / مصطفى احمد نعمه الله
الموضوع
Chronic Disease. Hepatitis C - therapy. Hepatitis C - physiopathology.
تاريخ النشر
2013.
عدد الصفحات
183 p. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
الكيمياء الحيوية (الطبية)
تاريخ الإجازة
1/1/2013
مكان الإجازة
جامعة المنصورة - كلية الطب - الكيمياء الحيوية الطبى
الفهرس
Only 14 pages are availabe for public view

from 203

from 203

Abstract

Liver transplantation can be life-saving for patients with end-stage liver disease. Before transplantation; patients with advanced liver disease were doomed to death within months to years. These patients now have the opportunity for extended survival with excellent quality of life after transplantation. The most common indication for LDLT in Egypt is HCV related cirrhosis, followed by HCC and the survival outcome is improving during the last five years. Many complications can occurs after liver transplantation, however, the main barriers to overcome in the early post operative period were immediate post-surgical survival together with prevention of acute rejection. Although immunosuppressive agent s and the regimens have been greatly extended and improved, allograft rejection still remains a major challenge in liver transplantation.
The aim of this study was to investigate if SNPs in TLR2 gene (Arg753Gln and Arg677Trp) contribute to the risk of developing ACR after liver transplantation. Moreover, we tested if these SNPs affect the expression of TLR2 gene or not by estimating serum TLR2 protein in liver transplanted recipients.
Methods: This study included 114 patients underwent adult living donor liver transplantation for chronic HCV infection in Gastroenterology Surgery Center. 99 patients were adult male in addition to 15 female patients. Patients were divided into two main groups: group I (case) (n=56): Acute cellular rejection (ACR) group including patients with at least one acute rejection episode during the first three months post transplantation. group II (control) (n=58): Non ACR group including patients with no acute rejection episode during the first three months post transplantation. Thorough history taking and complete routine investigations were performed for all patients recruited in this study and it was found that no statistically significant difference regarding demographic or clinical data were present between ACR and non ACR groups.
Results: Patients experienced ACR episode had higher frequency of heterozygote GA and homozygote mutant AA genotypes compared to non ACR patients. Mutant A allele of Arg753Gln was found to be significantly associated with risk of acute rejection when compared to wild-type G allele. Frequency of C/T genotype in liver transplanted patient’s experienced ACR episode is significantly higher than that in patients not experienced ACR. Mutant T allele of TLR2 Arg677Trp was significantly associated with increased risk of acute rejection when compared with C allele. Patients having one or both risky allele (A and/or T) had a higher significant risk for developing acute cellular rejection after liver transplantation compared to those who haven’t any risky alleles (CG haplotype).
Conclusion: Arg753Gln and Arg677Trp polymorphisms in TLR2 gene are associated with significantly increased risk of acute cellular rejection and thus can demonstrate a novel role for innate immunity in the pathobiology of acute cellular rejection after liver transplantation. This study identifies TLR2 Arg753Gln and Arg677Trp polymorphisms as novel immunologic markers that could be useful to identify a subpopulation of patients with a higher risk of rejection after liver transplantation for HCV-related cirrhosis.