Negative Predictive Value of IL28B, SLC28A2, and CYP27B1 SNPs and Low RBV Plasma Exposure for Therapeutic Response to PEG/IFN-RBV Treatment

被引：32

作者：

D'Avolio, Antonio ^{[1
]}

Ciancio, Alessia ^{[2
]}

Siccardi, Marco ^{[3
]}

Smedile, Antonina ^{[2
]}

Simiele, Marco ^{[1
]}

Cusato, Jessica ^{[1
]}

Baietto, Lorena ^{[1
]}

Marucco, Diego Aguilar ^{[1
]}

Cariti, Giuseppe ^{[1
]}

Calcagno, Andrea ^{[1
]}

de Requena, Daniel Gonzalez ^{[1
]}

Sciandra, Mauro ^{[1
]}

Troshina, Giulia ^{[2
]}

Caviglia, Gian Paolo ^{[2
]}

Bonora, Stefano ^{[1
]}

Rizzetto, Mario ^{[2
]}

Di Perri, Giovanni ^{[1
]}

机构：

[1] Univ Turin, Infect Dis Unit, Dept Med Sci, Amedeo Savoia Hosp, Turin, Italy

[2] S Giovanni Battista Molinette Hosp, Dept Gastroenterol, Turin, Italy

[3] Univ Liverpool, Dept Mol & Clin Pharmacol, Liverpool L69 3BX, Merseyside, England

来源：

THERAPEUTIC DRUG MONITORING | 2012年 / 34卷 / 06期

关键词：

HCV; therapeutic drug monitoring; ribavirin plasma exposure; single nucleotide polymorphisms; sustained virological response; SUSTAINED VIROLOGICAL RESPONSE; CHRONIC HEPATITIS-C; PEGINTERFERON ALPHA-2B; RIBAVIRIN THERAPY; GENETIC-VARIATION; SPONTANEOUS CLEARANCE; PLUS RIBAVIRIN; HCV GENOTYPE; HPLC-UV; VIRUS;

D O I：

10.1097/FTD.0b013e318272e55a

中图分类号：

R446 [实验室诊断]; R-33 [实验医学、医学实验];

学科分类号：

100118 [医学信息学]; 100208 [临床检验诊断学];

摘要：

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 mu g/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.

引用

页码：722 / 728

页数：7

共 53 条

[1]

IL28B in hepatitis C virus infection: translating pharmacogenomics into clinical practice [J].