Clinical milestones for the prediction of severe anemia by chronic hepatitis C patients receiving telaprevir-based triple therapy

Journal of Hepatology

Article in Press

Received 5 March 2013; received in revised form 19 April 2013; accepted 13 May 2013. published online 28 May 2013.
Accepted Manuscript

Eiichi Ogawa, Norihiro Furusyo, Makoto Nakamuta, Eiji Kajiwara, Hideyuki Nomura, Kazufumi Dohmen, Kazuhiro Takahashi, Takeaki Satoh, Koichi Azuma, Akira Kawano, Yuichi Tanabe, Kazuhiro Kotoh, Shinji Shimoda, Jun Hayashi The Kyushu University Liver Disease Study (KULDS) Group

Abstract

Background & aims

Anemia is a common adverse effect of telaprevir (TVR) in combination with pegylated interferon (PEG-IFN) α and ribavirin (RBV) therapy. It occurs at a higher incidence with the TVR relative to PEG-IFNα and RBV alone. We herein evaluate the baseline and on-treatment predictors of the development of severe anemia by chronic hepatitis C virus (HCV) patients receiving TVR-based triple therapy.

Methods

This prospective, multicenter study consisted of 292 patients (median age: 62 years) infected with HCV genotype 1. All received 12 weeks of TVR in combination with 24 weeks of PEG-IFNα2b and RBV. The definition of severe anemia during antiviral treatment is hemoglobin (Hb) <85 g/L.

Results

101 (34.6%) patients developed severe anemia during the treatment period. Multivariable logistic regression analysis of possible pretreatment predictors of the development of severe anemia extracted baseline Hb<135 g/L (Hazard ratio [HR], 2.53; P=0.0013), estimated glomerular filtration rate <80 mL/min/1.73m² (HR, 1.83; P=0.0265), and inosine triphosphatase (ITPA) CC genotype (rs1127354) (HR, 2.91; P=0.0024). For patients with ITPA CC (n=227), multivariable logistic regression analysis of possible pretreatment and on-treatment predictors of the development of severe anemia extracted Hb level at week 2 (HR, 0.96; P=0.0085) and the initial four weeks of weight-adjusted TVR (HR, 1.05; P=0.0281).

Conclusions

Anemia remains a risk for all patients treated with TVR-based triple therapy. However, ITPA polymorphism (rs1127354) is useful for predicting the development of severe anemia and will be helpful in the management of treatment.

Keywords: Hepatitis C virus, Anemia, Telaprevir, Inosine triphosohatase, Pegylated interferon, Ribavirin

Abbreviations: HCV, hepatitis C virus, PEG-IFN, pegylated interferon, RBV, ribavirin, SVR, sustained virological response, TVR, telaprevir, ITPA, inosine triphosphatase, SNP, single nucleotide polymorphism, Hb, hemoglobin, eGFR, estimated glomerular filtration rate, RVR, rapid virological response, HR, hazard ratio, CI, confidence interval, AUROC, area under the receiver operating characteristic curve

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