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

Overview of attention for article published in Hepatology, April 2014
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Title
ITPA genotype protects against anemia during peginterferon and ribavirin therapy but does not influence virological response
Published in
Hepatology, April 2014
DOI 10.1002/hep.27022
Pubmed ID
Authors

Jacinta A. Holmes, Stuart K. Roberts, Rachel J. Ali, Gregory J. Dore, William Sievert, Geoffrey W. McCaughan, Darrell H. Crawford, Wendy S. Cheng, Martin D. Weltman, Sara Bonanzinga, Kumar Visvanathan, Vijaya Sundararajan, Paul V. Desmond, D. Scott Bowden, Gail V. Matthews, Alexander J. Thompson, on behalf of the CHARIOT Study Group

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 < 0.0001). ITPase deficiency was present in 35%. ITPase deficiency strongly protected against Hb decline (P < 0.0001), but was not associated with SVR (P = 0.28). The probability of SVR increased with lower nadir Hb for both wild-type and deficient ITPase activity, but the association curve shifted to describe a parallel relationship at higher Hb levels in patients with ITPase deficiency. In a subset (n = 203), we tested the hypothesis that the association between Hb decline and SVR reflected RBV levels rather than actual Hb level. RBV levels were associated with on-treatment Hb decline and SVR, but not ITPase activity. In regression models, adjustment for RBV levels attenuated the association between Hb decline and SVR. Conclusion: ITPase deficiency protects against RBV-induced anemia, but is not associated with SVR. Our data suggest that the relationship between Hb decline and SVR is not mechanistic, but is linked to RBV levels. (Hepatology 2014;59:2152-2160).

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Geographical breakdown

Country Count As %
Unknown 16 100%

Demographic breakdown

Readers by professional status Count As %
Student > Postgraduate 4 25%
Professor > Associate Professor 4 25%
Researcher 3 19%
Student > Master 2 13%
Professor 1 6%
Other 1 6%
Unknown 1 6%
Readers by discipline Count As %
Medicine and Dentistry 10 63%
Agricultural and Biological Sciences 2 13%
Biochemistry, Genetics and Molecular Biology 1 6%
Unknown 3 19%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 January 2014.
All research outputs
#20,656,161
of 25,373,627 outputs
Outputs from Hepatology
#8,102
of 9,093 outputs
Outputs of similar age
#178,041
of 241,808 outputs
Outputs of similar age from Hepatology
#92
of 140 outputs
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