Pharmacologie clinique et biopharmaceutique

Abstrait

Ribavirin Transporter [Ent1] Polymorphism is a Pretreatment Predictor of Virologic Response: The Specific Role of Donor Liver Transporter

Valerio Giannelli, Maurizio Simmaco, Luana Lionetto, Giovanna Gentile, Michela Giusto, Francesca Romana Ponziani, Antonio Gasbarrini, Ubaldo Visco-Comandini, Adriano Pellicelli, Stefano Ginanni Corradini, Antonio Molinaro, Elisa Biliotti, Manuela Merli and Gloria Taliani

The genetic polymorphism of Equilibrative Nucleoside Transporter 1 [ENT1] is involved in ribavirin cellular uptake and it could positively enhance antiviral treatment response. The liver transplant setting offers the unique opportunity to selectively observe the effect(s) of the donor liver ENT1 gene on HCV treatment outcome. We aimed at studying donor polymorphism of ENT1 and HCV therapy outcome in transplanted patients. The role of ribavirin plasma concentration was evaluated. 39 patients after HCV recurrence were included. Genotyping of donor ENT1 and of IL-28B was performed in donor liver samples by RNA PCR. Allelic frequencies of liver ENT1 were: AA 43.6%; AG 28.2%; GG 28.2%. GG genotype was associated with rapid [RR=8; 95% CI 1.6-38; p=0.01] and sustained virological response [RR=9.5; 95% CI 1.6-53; p=0.01]. In multivariate analysis, GG genotype and a ribavirin plasma concentration >2.0 ng/mL at week 12 were independently associated with sustained virological response. In conclusion, the genetic polymorphism of ENT influences treatment response and a pre-treatment determination of its activity could help to predict treatment response in HCV patients.