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An index to predict ribavirin-induced anemia in asian patients with chronic genotype 1 hepatitis C.

ABSTRACT: BACKGROUND:Single-nucleotide polymorphisms (SNP) in the inosine triphosphate pyrophosphatase (ITPA) gene correlate with ribavirin (RBV)-induced anemia in patients with chronic hepatitis C (CHC) receiving combination therapy. Managing anemia is an early priority in the treatment process. OBJECTIVES:The aim was to develop a predictive index based on ITPA SNP status to identify CHC patients at risk of anemia. PATIENTS AND METHODS:A total of 418 eligible East Asian patients diagnosed with CHC genotype 1 (G1) received combination therapy in this study. Participant DNA was genotyped for a functional ITPA SNP (C/C, A/A or C/A) on chromosome 20 at rs1127354. A predictive index was constructed by incorporating independent factors identified for severe anemia events (hemoglobin < 10 g/dL). Areas under the receiver-operating characteristic curves (AUCs) represented the diagnostic accuracies of the predictive index in randomly assigned development and validation cohorts. RESULTS:Multiple logistic regressions identified age (? 50 y: OR = 9.7, 95% CI = 5.0 - 18.6), ITPA rs1127354 (C/C: OR = 3.3, 95% CI = 1.8 - 5.8) and baseline hemoglobin (< 14.0 g/dL: OR 6.4, 95% CI = 3.3 - 12.1; 14.0 - 14.9: OR = 2.4, 95% CI = 1.2 - 4.6) as predictors of severe anemia throughout the treatment. For severe anemia, the predictive index incorporating age, ITPA SNP status and baseline hemoglobin yielded diagnostic accuracies (AUCs) of 0.830 (95% CI = 0.783 - 0.871) in the development (n = 324) and 0.902 (0.826 - 0.925) in the validation (n = 81) cohorts. CONCLUSIONS:In patients with CHC G1 and receiving combination therapy, ITPA SNP-based index was an accurate and practical solution for prediction of severe anemia.

SUBMITTER: Chen SH

PROVIDER: S-EPMC4377223 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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An index to predict ribavirin-induced anemia in asian patients with chronic genotype 1 hepatitis C.

Chen Sheng-Hung SH Peng Cheng-Yuan CY Lai Hsueh-Chou HC Su Wen-Pang WP Lin Chia-Hsin CH Li Yu-Fen YF Chuang Po-Heng PH Chen Ching-Hsiang CH

Hepatitis monthly 20150320 3

<h4>Background</h4>Single-nucleotide polymorphisms (SNP) in the inosine triphosphate pyrophosphatase (ITPA) gene correlate with ribavirin (RBV)-induced anemia in patients with chronic hepatitis C (CHC) receiving combination therapy. Managing anemia is an early priority in the treatment process.<h4>Objectives</h4>The aim was to develop a predictive index based on ITPA SNP status to identify CHC patients at risk of anemia.<h4>Patients and methods</h4>A total of 418 eligible East Asian patients dia ...[more]

PMID: 25834588

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Project description:The current standard of care for hepatitis C virus (HCV) infection - combination therapy with pegylated interferon and ribavirin - elicits sustained responses in only ?50% of the patients treated. No alternatives exist for patients who do not respond to combination therapy. Addition of ribavirin substantially improves response rates to interferon and lowers relapse rates following the cessation of therapy, suggesting that increasing ribavirin exposure may further improve treatment response. A key limitation, however, is the toxic side-effect of ribavirin, hemolytic anemia, which often necessitates a reduction of ribavirin dosage and compromises treatment response. Maximizing treatment response thus requires striking a balance between the antiviral and hemolytic activities of ribavirin. Current models of viral kinetics describe the enhancement of treatment response due to ribavirin. Ribavirin-induced anemia, however, remains poorly understood and precludes rational optimization of combination therapy. Here, we develop a new mathematical model of the population dynamics of erythrocytes that quantitatively describes ribavirin-induced anemia in HCV patients. Based on the assumption that ribavirin accumulation decreases erythrocyte lifespan in a dose-dependent manner, model predictions capture several independent experimental observations of the accumulation of ribavirin in erythrocytes and the resulting decline of hemoglobin in HCV patients undergoing combination therapy, estimate the reduced erythrocyte lifespan during therapy, and describe inter-patient variations in the severity of ribavirin-induced anemia. Further, model predictions estimate the threshold ribavirin exposure beyond which anemia becomes intolerable and suggest guidelines for the usage of growth hormones, such as erythropoietin, that stimulate erythrocyte production and avert the reduction of ribavirin dosage, thereby improving treatment response. Our model thus facilitates, in conjunction with models of viral kinetics, the rational identification of treatment protocols that maximize treatment response while curtailing side effects.

Dataset Information

An index to predict ribavirin-induced anemia in asian patients with chronic genotype 1 hepatitis C.

Publications

An index to predict ribavirin-induced anemia in asian patients with chronic genotype 1 hepatitis C.

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