We read with great interest the article by Holmes et al. published in Hepatology. The researchers conclude that inosine triphosphatase (ITPase) deficiency protects against ribavirin (RBV)-induced anemia, but that it is not associated with sustained virological response (SVR) to pegylated interferon (Peg-IFN)-α-2a/RBV therapy in HCV genotype 1 (HCV-1)-infected patients from the CHARIOT study.
Rapid virological response (RVR) has been considered the most important predictor for SVR, and an abbreviated treatment regimen was encouraged in patients with RVR and a low viral load.[2, 3] We wonder whether RVR (32.8%) had any effect on the result of the association between SVR and hemoglobin decline or upon RBV pharmacokinetics in the study by Holmes et al. It is known that plasma RBV levels at week 8, rather than the actual hemoglobin levels or ITPase deficiency in patients with HCV-11 and genotype 2/3 infection,[1, 4] have been associated with SVR. Since the very important role of the genetic variation in interleukin (IL)28B on predicting response to Peg-IFN-based therapies either without[3, 5, 6] or with new direct antiviral agents has been recognized, it seems also necessary to take the IL28B genotype into consideration in elucidating the influence of RBV levels on SVR in HCV-1 patients, without otherwise detracting from the results by Holmes et al.