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We thank Professor Yu and colleagues for their interest in our study.1 In the CHARIOT (Collaborative group HepAtitis C study using PegasysRBV Induction dose in genOType one) study of 871 patients, we showed that patients with anemia or a hemoglobin decline of >30 g/L from baseline had higher sustained virological response (SVR) rates compared to those who did not experience similar hematological changes. A similar outcome was reported from the IDEAL (Individualized Dosing Efficacy Versus Flat Dosing to Assess Optimal Pegylated Interferon Therapy) study of 3023 patients.2 Both study populations were primarily Caucasian. Yu and colleagues examined a subset of 100 patients from a total study population of 200 Taiwanese patients treated with pegylated interferon and ribavirin for 48 weeks and found a higher rate of anemia development (45%) and a similar rate of patients with a hemoglobin decline of >30 g/L from baseline (78%). There was no significant difference in SVR rates between patients with and patients without the hematological changes. We therefore further analyzed the CHARIOT study population stratified by ethnicity (Asian, n = 118 versus non-Asian, n = 778). Asian patients were more likely to develop anemia than non-Asians (27% versus 14%, P < 0.001) but had a similar likelihood of hemoglobin decline >30 g/L from baseline (71% versus 74%, P = 0.494). Within the Asian population, SVR rates were not significantly higher for those with anemia (71% versus 59%, P = 0.188) or those with hemoglobin decline >30 g/L from baseline (74% versus 66%, P = 0.379). Within the non-Asian population, SVR rates were higher for those with anemia (57% versus 46%, P = 0.036) and those with hemoglobin decline >30 g/L from baseline (51% versus 36%, P < 0.001). These contrasting levels of significance may relate to sample size, because the SVR differential for the impact of anemia was similar in the Asian (12%) and non-Asian (11%) populations.

An alternative explanation, as proposed by Yu et al., may relate to the higher proportion of patients with a favorable interleukin-28B (IL28B) genotype,3 leading to an overall higher SVR rate. Although the SVR rate within the CHARIOT Asian population was not as high as in the Taiwanese study (79%) it was significantly higher than the non-Asian population (68% versus 47%, P < 0.001). Ultimately, multivariate analysis including IL28B genotype and on-treatment anemia in a large treatment population will be required to conclusively demonstrate the relative influence of each factor on treatment outcome.4

References

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  • 1
    Sievert W, Dore GJ, McCaughan GW, Yoshihara M, Crawford DH, Cheng W, et al. Virological response is associated with decline in hemoglobin concentration during pegylated interferon and ribavirin therapy in HCV genotype 1. HEPATOLOGY 2011; doi:10.1002/hep.24180.
  • 2
    Sulkowski M, Shiffman M, Afdhal N, Reddy K, McCone J, Lee W, et al. Hepatitis C virus treatment-related anemia is associated with higher sustained virologic response rate. Gastroenterology 2011; 139: 1602-1611.
  • 3
    Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 2009; 461: 399-401.
  • 4
    Thompson AJ, Muir AJ, Sulkowski M, Ge D, Fellay J, Shiana KV, et al. Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology 2011; 139: 120-129.

William Sievert M.D.*, Gregory J. Dore B.Sc., M.B., B.S.†, Stuart K. Roberts M.D.‡, * Gastroenterology and Hepatology Unit, Monash Medical Centre and Centre for Inflammatory Diseases, Monash University, Melbourne, Australia, † National Centre in HIV Epidemiology and Clinical Research, University of New South Wales and St Vincent's Hospital, Sydney, Australia, ‡ Alfred Hospital, Melbourne, Victoria, Australia.