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Inosine Triphosphatase Polymorphisms and Ribavirin Pharmacokinetics as Determinants of Ribavirin-Associate Anemia in Patients Receiving Standard Anti-HCV Treatment.
MedLine Citation:
PMID:  22406654     Owner:  NLM     Status:  Publisher    
BACKGROUND: Functional variants of inosine triphosphatase (ITPA) were recently found to protect against ribavirin (RBV)-induced hemolytic anemia. However, no definitive data are yet available on the role of plasma RBV concentrations on hemoglobin (Hb) decrement. Moreover, no data have been published on the possible interplay between these 2 factors. METHODS: A retrospective analysis included 167 patients. The ITPA variants rs7270101 and rs1127354 were genotyped and tested using the χ test for association with Hb reduction at week 4. We also investigated, using multivariate logistic regression, the impact of RBV plasma exposure on Hb concentrations. RESULTS: Both single nucleotide polymorphisms were associated with Hb decrease. The carrier of at least 1 variant allele in the functional ITPA single nucleotide polymorphisms was associated with a lower decrement of Hb (-1.1 g/dL), as compared with patients without a variant allele (-2.75 g/dL; P = 4.09 × 10). RBV concentrations were not influenced by ITPA genotypes. A cut-off of 2.3 μg/mL of RBV was found to be associated with anemia (area-under-receiver operating characteristic = 0.630, sensitivity = 50.0%, and specificity = 69.5%, P = 0.008). In multivariate logistic regression analyses, the carrier of a variant allele (P = 0.005) and plasma RBV concentrations <2.3 μg/mL (P = 0.016) were independently associated with protection against clinically significant anemia at week 4. CONCLUSIONS: Although no direct relationship was found between ITPA polymorphisms and plasma RBV concentrations, both factors were shown to be significantly associated with anemia. A multivariate regression model based on ITPA genetic polymorphisms and RBV trough concentration was developed for predicting the risk of anemia. By relying upon these 2 variables, an individualized management of anemia seems to be feasible in recipients of pegylated interferon-RBV therapy.
Antonio Dʼavolio; Alessia Ciancio; Marco Siccardi; Antonina Smedile; Lorena Baietto; Marco Simiele; Diego Aguilar Marucco; Giuseppe Cariti; Andrea Calcagno; Daniel Gonzalez de Requena; Mauro Sciandra; Jessica Cusato; Giulia Troshina; Stefano Bonora; Mario Rizzetto; Giovanni Di Perri
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-7
Journal Detail:
Title:  Therapeutic drug monitoring     Volume:  -     ISSN:  1536-3694     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-3-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7909660     Medline TA:  Ther Drug Monit     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
*Department of Infectious Diseases, University of Turin, Amedeo di Savoia Hospital †Department of Gastroenterology, S. Giovanni Battista (Molinette) Hospital, Turin, Italy.
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