Several factors including ITPA polymorphism influence ribavirin-induced anemia in chronic hepatitis C

作     者：Akihito Tsubota Noritomo Shimada Hiroshi Abe Kai Yoshizawa Rie Agata Yoko Yumoto Makiko Ika Yoshihisa Namiki Keisuke Nagatsuma Hiroshi Matsudaira Kiyotaka Fujise Norio Tada Yoshio Aizawa 

作者机构：Institute of Clinical Medicine and ResearchThe Jikei University School of Medicine163-1 Kashiwa-shitaKashiwaChiba 277-8567Japan Division of Gastroenterology and HepatologyKashiwa HospitalThe Jikei University School of Medicine163-1 Kashiwa-shitaKashiwaChiba 277-8567Japan Department of GastroenterologyShinmatsudo Central General Hospital1-380 ShinmatsudoMatsudoChiba 270-0034Japan Division of Gastroenterology and HepatologyKatsushika Medical CenterThe Jikei University School of Medicine6-41-2 AotoKatsushika-kuTokyo 125-8506Japan 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2012年第18卷第41期

页      面：5879-5888页

核心收录：

学科分类：1004[医学-公共卫生与预防医学(可授医学、理学学位)] 100401[医学-流行病与卫生统计学] 10[医学] 

基　　金：Supported by Clinical Research Funds from Division of Gastroenterology and Hepatology Katsushika Medical Center The Jikei University School of Medicine 

主　　题：Chronic hepatitis C virus infection Ribavi-rin Pegylated interferon Prediction model Hemolyticanemia Single nucleotide polymorphism 

摘      要：AIM： To construct formulae for predicting the likelihood of ribavirin-induced anemia in pegylated interferon plus ribavirin for chronic hepatitis C. METHODS： Five hundred and sixty-one Japanese patients with hepatitis C virus genotype lb who had received combination treatment were enrolled and as- signed randomly to the derivation and confirmatory groups. Single nucleotide polymorphisms at or nearby ITPA were genotyped by real-time detection poly- merase chain reaction. Factors influencing significant anemia （hemoglobin concentration 〈 10.0 g/dL at week 4 of treatment） and significant hemoglobin decline （declining concentrations 〉 3.0 g/dL at week 4） were analyzed using multiple regression analyses. Prediction formulae were constructed by significantly independent factors. RESULTS： Multivariate analysis for the derivation group identified four independent factors associated with significant hemoglobin decline： hemoglobin decline at week 2 [P = 3.29× 10^4, odds ratio （OR） = 7.54 （g/dL）], estimated glomerular filtration rate [P = 2.16× 10^4, OR = 0.962 （ml/min/1.73 m2）], rs1127354 （P = 5.75 × 10^4, OR = 10.94） and baseline hemoglobin [P = 7.86 × 10^4, OR = 1.50 （g/alL）]. Using the model constructed by these factors, positive and negative predictive values and predictive accuracy were 79.8%, 88.8% and 86.2%, respectively. For the confirmatory group, they were 83.3%, 91.0% and 88.3%. These factors were closely correlated with significant anemia. However, the model could not be constructed, because no patients with rs1127354 minor genotype CA/AA had significant anemia. CONCLUSION： Reliable formulae for predicting the likelihood of ribavirin-induced anemia were constructed. Such modeling may be useful in developing individual tailoring and optimization of ribavirin dosage.