Document Detail

Negative Predictive Value of IL28B, SLC28A2, and CYP27B1 SNPs and Low RBV Plasma Exposure for Therapeutic Response to PEG/IFN-RBV Treatment.
MedLine Citation:
PMID:  23149444     Owner:  NLM     Status:  Publisher    
OBJECTIVES:: The response rate to treatment of chronic hepatitis C virus-genotype 1 and 4 infections was recently found to be strongly influenced by many polymorphisms. The aim of our study was to carry out an integrated analysis of the effects of polymorphisms and ribavirin (RBV) plasma exposure on outcome. METHODS:: The retrospective analysis included 174 patients. IL28B, CYP27B1, SLC29A1, SLC28A3, and SLC28A2 polymorphisms were genotyped and tested for association with sustained virological response. The impact of RBV plasma exposure during the first 3 months of therapy on outcome was also investigated. RESULTS:: Considering patients infected by hepatitis C virus-1/4, 3 polymorphisms (IL28B rs8099917TT, CYP27B1 rs4646536TT, and CNT2 rs11854484TT) were associated with sustained virological response. The number of negative variant allele and low RBV exposure were correlated to percentage increasing to therapy failure, suggesting some degree of cumulative effect of the 4 factors. A cutoff of 2.5 μg/mL of RBV was found to be associated with outcome (area under ROC [AUROC] curve = 0.64, sensitivity = 55.0%, and specificity = 71.2%, P = 0.020). In multivariate logistic regression analyses, each variant allele and RBV plasma exposure cutoff were independently associated with outcome. CONCLUSIONS:: In this study, we found that additional polymorphisms and RBV plasma exposure are also able to influence the achievement of response. Regardless of the magnitude of RBV pharmacokinetic exposure, the negative predictive value of the polymorphisms here investigated is much stronger than the positive one.
Antonio Dʼavolio; Alessia Ciancio; Marco Siccardi; Antonina Smedile; Marco Simiele; Jessica Cusato; Lorena Baietto; Diego Aguilar Marucco; Giuseppe Cariti; Andrea Calcagno; Daniel Gonzalez de Requena; Mauro Sciandra; Giulia Troshina; Gian Paolo Caviglia; Stefano Bonora; Mario Rizzetto; Giovanni Di Perri
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Publication Detail:
Journal Detail:
Title:  Therapeutic drug monitoring     Volume:  34     ISSN:  1536-3694     ISO Abbreviation:  Ther Drug Monit     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7909660     Medline TA:  Ther Drug Monit     Country:  -    
Other Details:
Languages:  ENG     Pagination:  722-728     Citation Subset:  -    
*Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy †Department of Gastroenterology, S. Giovanni Battista (Molinette) Hospital, Turin, Italy ‡Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom.
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