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To the Editor:

We read with great interest the article in Hepatology by Sievert et al.,1 which retrospectively evaluated the CHARIOT study of 871 treatment-naive patients who were infected with hepatitis C virus (HCV) genotype 1 (HCV-1) to determine whether hemoglobin decline is associated with sustained virological response (SVR) achieved through pegylated interferon (PegIFN) and ribavirin treatment. With 16% of patients developing anemia (serum hemoglobin <100 g/L) and 76% of patients developing a hemoglobin decline of >30 g/L from baseline, SVR rate was higher in anemic patients compared to those without anemia (61% versus 50%, respectively; P = 0.02). The authors concluded that the development of anemia or experience of a decline in hemoglobin of >30 g/L predicts better SVR in HCV-1 patients who receive PegIFN/ribavirin treatment which has also been reported in the post hoc analysis of the IDEAL study by Sulkowski et al. (74%).2

We examined the 100 Taiwanese HCV-1 patients who received 48-week PegIFN/ribavirin treatment in our randomized trial that enrolled a total of 200 patients.3 The means (±standard deviations) for baseline, lowest, and decline of hemoglobin levels were 146 ± 14 g/L, 103 ± 17 g/L, and 42 ± 14 g/L, respectively. We found 45% of patients developed anemia (serum hemoglobin <100 g/L) and 78% developed hemoglobin decline of >30 g/L from baseline. With 79 patients (79%) achieving SVR, the SVR rate was similar between patients with and without anemia (77.8% versus 80%, P = 0.786). Also, the SVR rate in patients with hemoglobin decline >30 g/L was similar compared to patients without hemoglobin decline >30 g/L (78.2% versus 81.8%, P = 1.000). The means (±standard deviations) for baseline, lowest, and decline of hemoglobin level were similar between patients with and without SVR (146 ± 13 g/L versus 143 ± 15 g/L, P = 0.286; 104 ± 17 versus 102 ± 19 g/L, P = 0.670; 43 ± 14 versus41 ± 14 g/L, P = 0.600). The treatment-related anemia seems to play a minimal role in predicting SVR in Taiwanese patients infected with HCV-1.

We showed the percentage of hemoglobin decline >30 g/L (78%) in Taiwanese patients who received PegIFN/ribavirin treatment without erythropoietin was similar to reports by Sievert et al. (76%) and Sulkowski et al. (74%). Nevertheless, we reported a higher percentage (45%) of anemia (serum hemoglobin <100 g/L) in Taiwanese patients than that reported by Sievert et al. (16%)1 and Sulkowski et al. (29%).2 In addition to the lack of erythropoietin use in our study, another major reason for the higher rate of ribavirin-related anemia may be due to the significantly lower body weight (67.5 kg) of our patients than those of Sievert et al. (77.9 kg) and Sulkowski et al. (83.4 kg), leading to relatively higher initial ribavirin exposure (up to 15 mg/kg body weight/day).2 The high ribavirin exposure—just as the water that bears the boat is the same that swallows it up—may induce more anemia during treatment but leads to a higher SVR rate. In addition, the recent novel finding showed Asian patients have the highest frequency of the advantageous genotype in the gene region encoding interleukin-28B (IL-28B, also called IFNλ3), which is a very strong predictor of treatment response.4 We have recently conducted a large-scale study5 to test 552 Taiwanese HCV-1 patients; of these, 469 (85.0%) have favorable rs8099917, located ∼8 kilobases upstream of the IL-28B TT genotype, which enhances the treatment outcome in HCV-1 infection6, 7 and is associated with the rapid virological response in HCV genotype 2 infection in Taiwanese patients.8 Taken together, it is not difficult to understand why Taiwanese HCV-1 patients have a high SVR rate with PegIFN/ribavirin therapy. We consider that such a good response in Taiwanese HCV-1 patients might also possibly contribute to minimizing the role of anemia on predicting the treatment outcome shown by Sievert et al.1 and Sulkowski et al.,2 and further studies are needed.

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
    Yu ML, Dai CY, Huang JF, Chiu CF, Yang YH, Hou NJ, et al. Rapid virological response and treatment duration for chronic hepatitis C genotype 1 patients: A randomized trial. HEPATOLOGY 2008; 47: 1884-1893.
  • 4
    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.
  • 5
    Huang CF, Dai CY, Huang JF, Chuang WL, Yu ML. The linkage of hepatitis C viral genotype and interleukin-28B genetic polymorphisms in Asian patients. HEPATOLOGY 2011; 53: 367-368.
  • 6
    Tanaka Y, Nishida N, Sugiyama M, Kurosaki M, Matsuura K, Sakamoto N, et al. Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet 2009; 41: 1105-1109.
  • 7
    Suppiah V, Moldovan M, Ahlenstiel G, Berg T, Weltman M, Abate ML, et al. IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet 2009; 41: 1100-1104.
  • 8
    Yu ML, Huang CF, Huang JF, Chang NC, Yang JF, Lin ZY, et al. Role of interleukin-28B polymorphisms in the treatment of hepatitis C virus genotype 2 infection in Asian patients. HEPATOLOGY 2011; 53: 7-13.

Chia-Yen Dai M.D., Ph.D.* ‡, Chung-Feng Huang M.D., M.S.* † ¶, Jee-Fu Huang M.D.* § **, Wan-Long Chuang M.D., Ph.D.* §, Ming-Lung Yu M.D., Ph.D.* § ¶, * Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, † Hepatobiliary Division, Department of Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, ‡ Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, § Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ¶ Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan, ** Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan.