A crossing in therapy for hepatitis C virus genotype 2 or 3: Increasing ribavirin dose with shortened duration or reducing ribavirin dose with standard duration
Authors: Chung-Feng Huang, Chia-Yen Dai, Jee-Fu Huang, Wan-Long Chuang, Ming-Lung Yu
Journal: Hepatology (2009)

We read with great interest the article in a recent issue of HEPATOLOGY.1 Ferenci et al. reported that 68.8% (97/141) and 63.8% (90/141) of treatment-naïve patients infected with hepatitis C virus (HCV) genotype 2 or 3 (HCV-2, HCV-3) achieved a sustained virological response (SVR) after 24 weeks of treatment with ribavirin 800 mg/day (group A) and 400 mg/day (group B), respectively, plus peginterferon alfa-2a (PegIFN) 180 μg/week. In group A more than group B patients, the rate of SVR was similar among patients infected with HCV-3 (67.5% versus 63.9%), but the rate of SVR was significantly higher (77.8% versus 55.6%) among patients infected with HCV-2. The authors concluded that when administered for 24 weeks with PegIFN, ribavirin doses of 400 and 800 mg/day produce equivalent outcomes in patients infected with HCV-3. Rapid virological response (RVR), defined as achieving seronegativity for HCV RNA at week 4 of treatment, has become the most important virological factor in predicting response to the treatment of chronic hepatitis C.2 In spite of standard therapy for 24 weeks, shortening the duration of combination therapy for patients infected with HCV-2 or HCV-3 with RVR has been suggested recently. Among patients with RVR, shortened regimens with higher dose of ribavirin per body weight had considerably higher rates of SVR than that with lower dose of ribavirin exposure by body weight (90%–100% versus 71%–79%, respectively).3-6 Di Martino et al. have reported the effect of a 16-week course of therapy together with a weight-based ribavirin regimen that seems equivalent to a 24-week treatment duration with fixed dosing of ribavirin at 800 mg/day.7 The rates of RVR were higher with a higher dose of ribavirin per body weight (78%–93%)3, 4, 8 when compared to that with lower doses of ribavirin per body weight (62%–65%).5, 6 Furthermore, low body weight,9 higher ribavirin dose,10 and the first 4 weeks of weight-based ribavirin exposure (>13 mg/kg/day)11 have been associated with the achievement of an RVR. These reports implicate that providing optimal dose of weight-based exposure of ribavirin is pivotal in the treatment of chronic hepatitis C. Although ribavirin doses of 400 and 800 mg/day produce equivalent efficacy in the study by Ferenci and coworkers,1 it raises concerns that reduced dose to fixed 400 mg/day (5.5 mg/kg/day) or even 800 mg/day (11.3 mg/kg/day) of ribavirin possibly are "suboptimal" doses to achieve a maximum RVR rate. On the other hand, the regimen with shortened duration and weight-based ribavirin dose has reduced the cost compared to 400 or 800 mg/day regimen for 24 weeks. Taken together, further studies are warranted, when we face the choice in the treatment of patients with HCV-2 or HCV-3 with RVR, to shed light on the alternatives of either shortening the duration with weight-based ribavirin dose or reducing the ribavirin dose with 24 weeks duration. Chung-Feng Huang*, Chia-Yen Dai* , Jee-Fu Huang* , Wan-Long Chuang* , Ming-Lung Yu* , * Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan.