In:
Antiviral Therapy, SAGE Publications, Vol. 16, No. 5 ( 2011-07), p. 685-694
Kurzfassung:
A genome-wide association study revealed an association between variants of the inosine triphosphatase ( ITPA) gene and ribavirin (RBV)-induced anaemia. The aim of this study was to replicate this finding in an independent Japanese cohort and to define a method to allow pretreatment prediction of anaemia in combination with other factors. Methods Genotype 1b chronic hepatitis C patients ( n=132) treated with pegylated interferon (PEG-IFN)-α and RBV for 48 weeks were genotyped for ITPA rs1127354 and examined for anaemia and treatment outcome. Results Variants of the ITPA gene protected against severe anaemia throughout the 48-week treatment period and were associated with lower incidence of anaemia-related RBV dose reduction. A combination of the ITPA genotype with baseline haemoglobin (Hb) and creatinine clearance (CLcr) levels predicted severe anaemia with high accuracy (90% sensitivity and 62% specificity). Among a subset of patients with the IL28B genotype of TT at rs8099917, patients with variants of the ITPA gene were associated with a higher rate of receiving 〉 80% of the expected RBV dose, a higher rate of sustained virological response (SVR), and a lower rate of relapse. Conclusions The variants of the ITPA gene, which could protect against haemolytic anaemia and RBV dose reduction, were associated with a high rate of SVR by standard PEG-IFN and RBV therapy in a subset of Japanese patients with the favourable TT genotype at rs8099917 of IL28B. A combination of ITPA genetic polymorphisms with baseline Hb and CLcr levels further improves the predictive accuracy of severe anaemia.
Materialart:
Online-Ressource
ISSN:
1359-6535
,
2040-2058
Sprache:
Englisch
Verlag:
SAGE Publications
Publikationsdatum:
2011
ZDB Id:
2118396-X
SSG:
15,3