ITPA genotype protects against anemia during peginterferon and ribavirin therapy but does not influence virological response

Jacinta A Holmes, Stuart Keith Roberts, Rachel J Ali, Gregory J Dore, William Sievert, Geoffrey McCaughan, Darrell Crawford, Wendy Cheng, Martin D Weltman, Sara Bonanzinga, Kumar Visvanathan, Vijaya Sundararajan, Paul V Desmond, David Scott Bowden, Gail V Matthews, Alexander Thompson

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24 Citations (Scopus)

Abstract

On-treatment anemia is associated with higher sustained virological response (SVR) rates during peginterferon plus ribavirin (RBV) therapy. Inosine triphosphatase (ITPA) variants causing ITPase deficiency have been shown to protect against RBV-induced anemia. However, ITPase activity has not been associated with SVR. To study this discrepancy, we examined the relationships between ITPase activity, on-treatment anemia, SVR, and RBV levels in hepatitis C virus genotype 1 (HCV-1) patients from the CHARIOT study. ITPA genotype (rs7270101, rs1127354) was used to define ITPase activity in 546 patients. Plasma RBV levels were measured using high-performance liquid chromatography (HPLC). Relationships between ITPase activity, on-treatment hemoglobin (Hb) levels, RBV levels, and SVR were tested using regression modeling, survival analysis, and locally weighted scatterplot smoothing (LOWESS) plot analysis. Hb decline was independently associated with SVR (P
Original languageEnglish
Pages (from-to)2152 - 2160
Number of pages9
JournalHepatology
Volume59
Issue number6
DOIs
Publication statusPublished - 2014

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