Clinical Pharmacology & Biopharmaceutics
Open Access

Research Article

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

Valerio Giannelli¹, Maurizio Simmaco², Luana Lionetto², Giovanna Gentile², Michela Giusto¹, Francesca Romana Ponziani³, Antonio Gasbarrini³, Ubaldo Visco-Comandini⁴, Adriano Pellicelli⁵, Stefano Ginanni Corradini¹, Antonio Molinaro¹, Elisa Biliotti⁶, Manuela Merli^1* and Gloria Taliani⁶

¹Department of Clinical Medicine, “Sapienza” University of Rome, Italy

²NESMOS Department, Advanced Molecular Diagnostic Unit, Sant’Andrea Hospital, Sapienza University of Rome, Italy

³Internal Medicine and Gastroenterology, Policlinico A Gemelli, Catholic University of Rome, Italy

⁴Infectious Disease and Hepatology, POIT San Camillo-INMI Lazzaro Spallanzani, Rome, Italy

⁵Epatologia, Ospedale San Camillo di Roma, Italy

⁶Tropical and Infectious Disease, Department of Clinical Medicine, “Sapienza” University of Rome, Italy

Corresponding Author:

Prof. Manuela Merli
Gastroenterology, Department of Clinical Medicine, “Sapienza” University of Rome, Via Filippo Turati, 33-37, 00185 Roma, Italy
Tel: 390649972001
E-mail: manuela.merli@uniroma1.it

Received Date: January 06, 2016; Accepted Date: September 20, 2016; Published Date: September 23, 2016

Citation: Giannelli V, Simmaco M, Lionetto L, Gentile G, Giusto M, et al. (2016) Ribavirin Transporter [Ent1] Polymorphism is a Pretreatment Predictor of Virologic Response: The Specific Role of Donor Liver Transporter. Clin Pharmacol Biopharm 5:163. doi: 10.4172/2167-065X.1000163

Copyright: © 2016 Giannelli V, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.

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