Possible determinants of rapid virological response suggesting shorter courses of combination therapy for hepatitis C virus genotype 2
Authors: Chia‐Yen Dai, Wan‐Long Chuang, Jee‐Fu Huang, Ming‐Yen Hsieh, Ming‐Lung Yu
Journal: Hepatology (2008)

Dalgard et al.1 reported the results of a randomized controlled trial for 428 chronic hepatitis C patients with genotype 2/3 infection treated with pegylated interferon alpha 2b (peginterferon-2b; 1.5 μg/kg) weekly and ribavirin (800–1400 mg) daily. Rapid virological response (RVR; undetectable hepatitis C virus RNA at week 4 of therapy) was obtained in 70.6% of patients, and 298 of them were randomized to 14 (n = 148) or 24 (n = 150) weeks of treatment. The authors reported a high sustained virological response (SVR) rate after 14 weeks of treatment (81.1%), although longer treatment may give slightly better SVR (90.7%), and they recommended treating patients with genotype 2 or 3 and RVR for only 14 weeks for economic savings and fewer side effects. The authors' report supported our previous results from a randomized controlled trial of Taiwanese chronic hepatitis C patients with genotype 2 infection, which showed that patients who had achieved an RVR had equal efficacy between 16 and 24 weeks of peginterferon-2a with weight-based ribavirin.2 Although some studies have also shown that a shorter course of therapy over 12–16 weeks with peginterferon/ribavirin is as effective as a 24-week course for genotype 2 patients with satisfactory response at week 4,3, 4 Shiffman et al.5 recently suggested that patients with genotype 2 or 3 should be treated for the currently recommended 24 weeks rather than 16 weeks, which seemed inferior to a fixed 24-week regimen. The different RVR rates between our patients and other studies seemed noteworthy. In Taiwanese genotype 2 patients, we found that an RVR was achieved by 86.7% of patients (86% and 87% in the 16-week and 24-week groups, respectively).2 The RVR rates for genotype 2 patients were 75.0% (45/60), 64.6% (137/212), and 69.2% (504/728) in Scandinavia,1 Italy,3 and United States,5 respectively. One of the possible causes of the RVR rate being higher among genotype 2 patients is that the mean body weight is lower in Taiwan (around 66 kg)2 than in Western countries (around 78,1 69,3 and 84 kg5). In addition to the higher mean initial dose of ribavirin (15–20 mg/kg/day for our patients), the higher initial dose of ribavirin administered by Dalgard et al.1 at a dosage of 800 to 1400 mg/day based on body weight (<65 kg, 800 mg/day; 65–85 kg, 1000 mg/day; 86–105 kg, 1200 mg/day; and >105 kg, 1400 mg/day) might lead to a higher RVR rate (75%) than the fixed initial daily dose (800 mg) with a highest mean body weight (around 84 kg) by Shiffman et al.5 The doses of peginterferon and ribavirin and RVR are all important factors for therapeutic response. A higher SVR rate was reported to be associated with higher average doses of peginterferon or ribavirin per kilogram of bodyweight by Manns et al.6 Reddy et al.7 reported that as long as patients achieved RVR, ribavirin dose reductions had minimal impact on SVR. Accordingly, determining whether a shorter course with a higher initial dose of ribavirin combined with peginterferon for genotype 2 patients may achieve a higher RVR rate and subsequently improve the SVR rate needs further randomized controlled trials. Chia-Yen Dai* , Wan-Long Chuang* , Jee-Fu Huang §, Ming-Yen Hsieh*, Ming-Lung Yu* §, * Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Department of Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, § Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan.