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

Research output: Contribution to journalArticleResearchpeer-review

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

Cite this

Holmes, Jacinta A ; Roberts, Stuart Keith ; Ali, Rachel J ; Dore, Gregory J ; Sievert, William ; McCaughan, Geoffrey ; Crawford, Darrell ; Cheng, Wendy ; Weltman, Martin D ; Bonanzinga, Sara ; Visvanathan, Kumar ; Sundararajan, Vijaya ; Desmond, Paul V ; Bowden, David Scott ; Matthews, Gail V ; Thompson, Alexander. / ITPA genotype protects against anemia during peginterferon and ribavirin therapy but does not influence virological response. In: Hepatology. 2014 ; Vol. 59, No. 6. pp. 2152 - 2160.
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title = "ITPA genotype protects against anemia during peginterferon and ribavirin therapy but does not influence virological response",
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",
author = "Holmes, {Jacinta A} and Roberts, {Stuart Keith} and Ali, {Rachel J} and Dore, {Gregory J} and William Sievert and Geoffrey McCaughan and Darrell Crawford and Wendy Cheng and Weltman, {Martin D} and Sara Bonanzinga and Kumar Visvanathan and Vijaya Sundararajan and Desmond, {Paul V} and Bowden, {David Scott} and Matthews, {Gail V} and Alexander Thompson",
year = "2014",
doi = "10.1002/hep.27022",
language = "English",
volume = "59",
pages = "2152 -- 2160",
journal = "Hepatology",
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Holmes, JA, Roberts, SK, Ali, RJ, Dore, GJ, Sievert, W, McCaughan, G, Crawford, D, Cheng, W, Weltman, MD, Bonanzinga, S, Visvanathan, K, Sundararajan, V, Desmond, PV, Bowden, DS, Matthews, GV & Thompson, A 2014, 'ITPA genotype protects against anemia during peginterferon and ribavirin therapy but does not influence virological response' Hepatology, vol. 59, no. 6, pp. 2152 - 2160. https://doi.org/10.1002/hep.27022

ITPA genotype protects against anemia during peginterferon and ribavirin therapy but does not influence virological response. / Holmes, Jacinta A; Roberts, Stuart Keith; Ali, Rachel J; Dore, Gregory J; Sievert, William; McCaughan, Geoffrey; Crawford, Darrell; Cheng, Wendy; Weltman, Martin D; Bonanzinga, Sara; Visvanathan, Kumar; Sundararajan, Vijaya; Desmond, Paul V; Bowden, David Scott; Matthews, Gail V; Thompson, Alexander.

In: Hepatology, Vol. 59, No. 6, 2014, p. 2152 - 2160.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - ITPA genotype protects against anemia during peginterferon and ribavirin therapy but does not influence virological response

AU - Holmes, Jacinta A

AU - Roberts, Stuart Keith

AU - Ali, Rachel J

AU - Dore, Gregory J

AU - Sievert, William

AU - McCaughan, Geoffrey

AU - Crawford, Darrell

AU - Cheng, Wendy

AU - Weltman, Martin D

AU - Bonanzinga, Sara

AU - Visvanathan, Kumar

AU - Sundararajan, Vijaya

AU - Desmond, Paul V

AU - Bowden, David Scott

AU - Matthews, Gail V

AU - Thompson, Alexander

PY - 2014

Y1 - 2014

N2 - 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

AB - 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

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U2 - 10.1002/hep.27022

DO - 10.1002/hep.27022

M3 - Article

VL - 59

SP - 2152

EP - 2160

JO - Hepatology

JF - Hepatology

SN - 0270-9139

IS - 6

ER -