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 hepatit...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.展开更多
基金Supported by Clinical Research Funds from Division of Gastroenterology and Hepatology,Katsushika Medical Center,The Jikei University School of Medicine
文摘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.