TY  - JOUR
A1  - Asselah, Tarik
A1  - Zeuzem, Stefan
A1  - Soriano, Vicente
A1  - Bronowicki, Jean-Pierre
A1  - Lohse, Ansgar W.
A1  - Müllhaupt, Beat
A1  - Schuchmann, Marcus
A1  - Bourlière, Marc
A1  - Buti, Maria
A1  - Roberts, Stuart K.
A1  - Gane, Edward J.
A1  - Stern, Jerry O.
A1  - Voss, Florian
A1  - Baum, Patrick
A1  - Gallivan, John-Paul
A1  - Böcher, Wulf Otto
A1  - Mensa, Federico J.
T1  - ITPA genotypes predict anemia but do not affect virological response with interferon-free faldaprevir, deleobuvir, and ribavirin for HCV infection
T2  - PLoS One
N2  - Background & aim: Whether inosine triphosphatase (ITPA) gene polymorphisms predict anemia during interferon-free therapy in chronic hepatitis C virus (HCV)-infected patients is unknown. We examined the relationship between two ITPA polymorphisms, anemia, and sustained virological response 12 weeks post-treatment (SVR12) in patients receiving the NS3/4A protease inhibitor faldaprevir, the non-nucleoside polymerase inhibitor deleobuvir, and ribavirin.
Methods: HCV genotype 1-infected, treatment-naïve patients (N = 362) were randomized and treated in one of five treatment arms with faldaprevir and deleobuvir with or without ribavirin. Two ITPA polymorphisms (rs1127354 and rs6051702) were genotyped and defined as ITPA-deficient (rs1127354 AA or AC; rs6051702 CC or CA) or ITPA-non-deficient (rs1127354 CC; rs6051702 AA) according to their association with ITPA deficiency. Baseline and on-treatment variables associated with anemia and SVR12 were identified using logistic regression.
Results: In the pooled ribavirin-containing arms, 10.1% (32/316) of patients experienced on-treatment hemoglobin <10 g/dL, and 32.6% (103/316) experienced on-treatment hemoglobin <10 g/dL or a change from baseline ≥3.5 g/dL. Of the latter group, 99% (102/103) had the ITPA-non-deficient rs1127354 genotype. Other variables associated with on-treatment hemoglobin <10 g/dL or a decrease ≥3.5 g/dL were age, baseline hemoglobin, rs6051702 genotype, and plasma ribavirin concentration. In a multivariate analysis, high plasma ribavirin concentration, low baseline hemoglobin, HCV genotype 1b, and IL28B genotype CC were associated with higher SVR12.
Conclusions: The ITPA rs1127354 CC and rs6051702 AA genotypes may predict ribavirin-induced anemia during treatment with interferon-free, ribavirin-containing regimens. With this interferon-free regimen, SVR was associated with ribavirin levels, but not with anemia or ITPA genotypes.
Y1  - 2015
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/39036
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-390368
SN  - 1932-6203
N1  - Copyright: © 2015 Asselah et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
VL  - 10
IS  - (12): e0144004
SP  - 1
EP  - 13
PB  - PLoS
CY  - Lawrence, Kan.
ER  -