ITPA Polymorphism Effects on Decrease of Hemoglobin During Sofosbuvir and Ribavirin Combination Treatment for Chronic Hepatitis C

Overview

Journal J Gastroenterol

Specialty Gastroenterology

Date 2016 Nov 9

PMID 27822709

Citations 8

Authors

Kei Morio

Michio Imamura

Yoshiiku Kawakami

Takashi Nakahara

Yuko Nagaoki

Tomokazu Kawaoka

Masataka Tsuge

Akira Hiramatsu

Hiroshi Aikata

Clair Nelson Hayes

Grace Naswa Makokha

Hidenori Ochi

Hajime Amano

Keiko Arataki

Takashi Moriya

Hiroyuki Ito

Keiji Tsuji

Hiroshi Kohno

Koji Waki

Toru Tamura

Toshio Nakamura

Kazuaki Chayama

Affiliations

Soon will be listed here.

Abstract

Background: Polymorphisms in the inosine triphosphatase (ITPA) gene is associated with anemia induced by peg-interferon (PEG-IFN) plus ribavirin (RBV) treatment for patients with chronic hepatitis C virus (HCV) infection. However, the effect of ITPA polymorphism on sofosbuvir plus RBV treatment is unknown.

Methods: Two hundred and forty-four patients with chronic HCV genotype 2 infection without decompensated liver cirrhosis were treated with sofosbuvir plus RBV for 12 weeks. The effects of ITPA polymorphism on hemoglobin levels and RBV dose reduction and treatment response were analyzed. ITPA (rs1127354) was genotyped using the Invader assay. Multivariate regression analysis was performed to identify factors associated with sustained virological response (SVR).

Results: Overall, SVR12 was achieved in 231 (94.7%) patients, based on intention to treat analysis. During the therapy, reduction of hemoglobin levels was significantly greater in ITPA genotype CC patients than CA/AA patients. Therefore, the cumulative proportion of patients with RBV dose reduction was significantly higher and total dose of RBV was significantly lower in patients with CC genotype compared to CA/AA genotypes. SVR12 rates were similar between ITPA genotypes CC and CA/AA (94.7 and 94.4%, respectively, P = 0.933). Multivariate logistic regression analysis identified FIB4 index <3.25 (odds ratio [OR], 9.388 for ≥3.25; P = 0.005) and low body weight (OR, 1.059, for high body weight; P = 0.017) as independent predictors for SVR12.

Conclusions: ITPA polymorphism influences hemoglobin levels and incidence of RBV dose reduction during sofosbuvir plus RBV therapy. However, ITPA genotype CC patients can expect a curative effect equivalent to CA/AA patients for chronic HCV genotype 2 infection.

Citing Articles

Impact of ITPA gene polymorphism for predicting anemia and treatment outcome in HCV infected patients taking Sofosbuvir Ribavirin therapy.

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Zidan A, Saad E, Ibrahim N, Hashem M, Mahmoud A, Hemeida A Heliyon. 2021; 7(5):e06908.

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Real-world effectiveness of sofosbuvir plus ribavirin for chronic hepatitis C genotype 2 in Asia: a systematic review and meta-analysis.

Wei B, Ji F, Yeo Y, Ogawa E, Zou B, Stave C BMJ Open Gastroenterol. 2018; 5(1):e000207.

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A facile PCR-RFLP method for genotyping of ITPA rs1127354 and rs7270101 polymorphisms.

Alavian S, Sharafi H, Shirmast P, Alavian S, Behnava B, Pouryasin M J Clin Lab Anal. 2018; 32(7):e22440.

PMID: 29660762 PMC: 6816863. DOI: 10.1002/jcla.22440.

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