THE PROBLEM OF VIRAL HEPATITIS IN LIVER TRANSPLANTATION

S.M. Iacob¹, V.R. Cicinnati², A. Dechene², C.G. Klein³, M. Lindemann⁴, G.C. Sotiropoulos³, A. Radtke⁵, I. Popescu⁶, G. Gerken², A. Paul³, S. Beckebaum^3
1Dept. Of General, Visceral And Transplantation Surgery And Dept. Of Gastroenterology And Hepatology, University Hospital Essen, Essen/GERMANY, ²Dept. Of Gastroenterology And Hepatology, University Hospital Essen, Essen/GERMANY, ³Dept. Of General, Visceral And Transplantation Surgery, University Hospital Essen, Essen/GERMANY, ⁴Institute For Transfusion Medicine, University Hospital Essen, Essen/GERMANY, ⁵Dept. Of General And Thoracic Surgery, University Hospital Schleswig Holstein, Campus Kiel, Kiel/GERMANY, ⁶, Fundeni Clinical Institute of Digestive Diseases and Liver Transplantation, Bucharest/ROMANIA

Body: Background: Hepatitis C Virus (HCV) reinfection after liver transplantation (LT) has a critical influence on graft and patient survival. Hepatic insulin resistance increases expression of the ATP-binding cassette (ABC) transporter G8 implicated in the regulation of cholesterol metabolism as well as the severity of HCV infection. Expression of multidrug resistance (MDR)1 gene expression has been shown to be increased in activated hepatic stellate cells in chronic liver diseases.
Aim: To assess predictive factors of severe HCV recurrence after LT.
Methods: We genotyped ABCG8 (C1199A and C1895T) and MDR1 (C3435T) in 165 LT recipients (46 with recurrent hepatitis C after LT, 119 controls transplanted for other liver diseases) by PCR-restriction fragment length polymorphism assay. Uni- and multivariate logistic regression analyses were used to identify predictors of severe HCV recurrence following LT.
Results: Analyses of single nucleotide polymorphisms (SNPs) revealed the following results: ABCG8 exon 8 C1199A (CC 69.1%, CA 29.7%, AA 1.2%), ABCG8 exon 13 C1895T (CC 46.1%, CT 44.2%, TT 9.7%), and MDR1 exon 26 C3435T (CC 22.4%, CT 40%, TT 37.6%). In the univariate analysis ABCG8 C1199C (p=0.006), MDR1 T3435T (p=0.03), presence of type 2 diabetes mellitus (p=0.01), acute rejection episodes (p=0.002), cytomegalovirus infection (p=0.005), lower cholinesterase (p=0.0003), higher direct bilirubin (p=0.03) and aspartate aminotransferase (p=0.01) were identified as predictors of severe HCV recurrence. Independent predictors of severe HCV recurrence included ABCG8 C1199C (p=0.01), MDR1 T3435T (p=0.03), presence of type 2 diabetes mellitus (p=0.03).
Conclusions: HCV LT recipients with ABCG8 and MDR1 polymorphisms have a significantly higher prevalence of advanced fibrosis. Active screening of these mutations may help to predict and to manage severe HCV recurrence in LT recipients.

Disclosure: All authors have declared no conflicts of interest.