Higher baseline Hb concentration was significantly associated with the likelihood of significant Hb decline. Conversely, lower www.selleckchem.com/products/CHIR-258.html baseline Hb concentration was linked to significant anemia. These findings may be a matter of course. However, most of this study population received treatment without RBV dose reduction as scheduled, suggesting that kinetics of Hb decline within the first 4 wk of treatment might be delayed in patients with lower baseline Hb concentration. A certain threshold of Hb concentration might limit the progression of anemia independent of baseline Hb concentration. At least in Japanese patients, the two different definitions of anemia, significant Hb decline and significant anemia, should be separately analyzed and discussed.

In this multivariate analysis, qualitative Hb decline at week 2 of treatment was most highly predictive of significant Hb decline, compared to the strong predictor ITPA SNP rs1127354 and other baseline factors. Previous studies have shown that Hb decline of 2.0 g/dL at week 2 of treatment was predictive of Hb concentration < 10 g/dL or < 8.5 g/dL during the treatment[12,20]. In another study, Hb decline of 1.5 g/dL at week 2 was predictive of Hb decline �� 2.5 g/dL at week 4[14]. In this ROC analysis, the best cutoff value for Hb decline at week 2 was 1.45 g/dL. Taken together, Hb decline at week 2 is an excellent early predictor of subsequent Hb decline and could identify candidates for early intervention to maintain RBV dosing and adequate exposure.

Indeed, the formula including this on-treatment variable improved positive and negative predictive values and predictive accuracy for significant anemia and significant Hb decline. When considered along with other independent baseline factors predictive of qualitative Hb decline at week 4, the final model yielded high significant values that represented goodness of fit. Using such a timely on-treatment variable and formula, more exact identification of patients prone to clinically significant anemia, early intervention with RBV dose reduction, and more careful monitoring may be indicated to reduce anemia-related adverse effects and avoid premature discontinuation of RBV. ITPA SNP rs1127354, baseline Hb concentration and estimated GFR influenced Hb decline at week 2 significantly and independently, as well as that at week 4.

However, it appears to be difficult to predict qualitative Hb decline at week 2 by using the multiple linear regression model. The Cilengitide point for attention is that the models and formulae did not perfectly predict the likelihood of the anemia, strongly suggesting the possibility that other unidentified factors associated with early occurring anemia might be lost, such as rare SNPs, brittleness of the RBC membrane against intracellular triphosphate form of RBV, or intracellular concentration of ITP.