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

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 1b who had received combination treatment were enrolled and assigned randomly to the derivation and confirmatory groups.Single nucleotide polymorphisms at or nearby ITPA were genotyped by real-time detection polymerase chain reaction.Factors influencing significant anemia(hemoglobin concentration 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 × 10-17,odds ratio(OR) = 7.54(g/dL)],estimated glomerular filtration rate [P = 2.16 × 10-4,OR = 0.962(mL/min/1.73 m 2)],rs1127354(P = 5.75 × 10-4,OR = 10.94) and baseline hemoglobin [P = 7.86 × 10-4,OR = 1.50(g/dL)].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.