We read with great interest the article published in a recent issue of HEPATOLOGY. 1 Shirakawa et al. enrolled 120 patients with chronic hepatitis C (CHC) infected with genotype 1 hepatitis C virus (HCV-1) and high baseline viral loads (HVL), defined by HCV RNA levels Υ 10 5 international units (IU)/mL measured by quantitative Cobas Amplicor assays (Roche Diagnostics Co. Ltd, Tokyo, Japan), who underwent combination therapy scheduled for 48 (85%) or 72 (15%) weeks. The authors concluded that the sequence of interferon sensitivity determining region of the HCV, the T-helper type 1 and type 2 (Th1/Th2) ratio, body weight, and neutrophil count can be useful for accurately predicting actual sustained virologic response (SVR) rate before combination therapy.
The definition of HVL (Υ 10 5 IU/mL) by the authors is not in accordance with the Asian Pacific Association for the Study of the Liver consensus statements (Υ 4 Ο« 10 5 IU/mL) 2 or other studies (Υ 8 Ο« 10 5 IU/mL). 3,4 Whether this definition influences the results deserves further study. The rates of rapid virologic response (RVR, defined as HCV RNA negative at week 4) and SVR were 45% and 21.7%, respectively, in their study. We examined the 200 Taiwanese patients with HCV-1 CHC in our randomized trial published recently 5 and found that 150 (75%) of these patients had serum HCV RNA Υ 10 5 IU/mL (HVL). The RVR and SVR rates of 150 patients were 64% and 34.7%, respectively, after receiving combination therapy with peginterferon alpha-2a plus oral ribavirin. A significantly higher SVR rate in patients treated for 48 weeks than 24 weeks (78.5%, 62 of 79 versus 35.4%, 34 of 71, P Ο½ 0.001) was observed. Recently, Ide et al. reported a 36% (20 of 56) SVR rate in Japanese patients with CHC and HVL treated with peginterferon alpha-2b/ribavirin for 48 weeks. 6 Accordingly, we have noticed the SVR rate and RVR rate in Taiwanese patients with HCV-1 with HVL treated for 24 or 48 weeks were higher than Japanese patients treated for 48 or 72 weeks. The important role of the weight-based ribavirin exposure during the first 4 weeks of combination therapy on the achievement of an RVR has been highlighted previously. 7 A cut-off point of 13 mg/kg/day of the first 4 weeks of weight-based ribavirin exposure have been reported associated with the achievement of an RVR. 8 Patients in the study by Shirakawa et al. would have an exposure of less than 13.1 mg/kg/day ribavirin exposure by 4 weeks (starting dose: for body weight 60 kg or less; 600 mg/day, 61 kg to 80 kg; 800 mg/day, 81 kg or more; 1000 mg/day) which is lower than 17.4 mg/kg/day (starting dose: for body weight 75 kg or less; 1000 mg/day, 75 kg or more; 1200 mg/day) in Taiwanese patients infected with HCV-1. We agree that the valuable finding of pretreatment predictors for SVR rate by Shirakawa et al. should be applauded. The relative low SVR and RVR rates, even with longer duration of treatment, compared to Taiwanese patients infected with HCV-1 with HVL raise a concern of relative suboptimal ribavirin exposure, and the actual role of these pretreatment predictors have to be confirmed by further studies.