Rapid virological response to peginterferon and ribavirin for hepatitis C genotype 1: The role of weight-based ribavirin exposure

Abstract

We read with great interest the report by Mangia et al. in a recent issue of HEPATOLOGY.1 They assigned 696 patients with hepatitis C virus genotype 1 (HCV-1) to peginterferon plus ribavirin 1000–1200 mg/day for 48 weeks (standard, n = 237) or for 24, 48, or 72 weeks if patients were HCV-RNA–negative at weeks 4, 8, or 12, respectively (variable, n = 459). The sustained virological response (SVR) was comparable between the standard group (45.1%) and the variable group (48.8%). Patients with rapid virological response (RVR; HCV-RNA–negative at weeks 4) achieved a high SVR rate with either standard 48-week (87.0%) or abbreviated 24-week (77.2%) treatment, respectively. However, only 26.7% of patients attained an RVR, indicating the urgency of increasing RVR rate to ensure treatment efficacy. Although the RVR rate in the study by Mangia et al. was substantially higher than those in previous reports from Europe and the United States (10%–22.6%),2-5 it was considerably lower than that of our recent study in Taiwan (43.5%).6 Similarly, the RVR rate of patients with HCV-2 was noticeably higher in Taiwanese patients (86.7%)7 than in whites (71.1%).8 Several factors have been predictors of an RVR for HCV-1, such as lower viremia,1, 5, 6 young age,1, 5, 9 and HCV-1b.2 However, these factors are unchangeable. Recently, ribavirin dose,2 low body weight,9 and the first 4 weeks of weight-based ribavirin exposure with a cut-off point of 13 mg/kg/day5 have been associated with the achievement of an RVR. These findings suggest the role of weight-based ribavirin exposure, an adjustable factor, in achieving an RVR. Table 1 summarizes the relationship among ribavirin dose, body weight, and RVR rate in patients with HCV-1 in recent large clinical trials. A regimen with the standard dose of ribavirin (1000–12000 mg/day) had a considerably higher rate of RVR (22.6%–43.5%) than that with a lower dose of ribavirin (800 mg/day, 10%–21.6%). Moreover, a negative linear trend was observed between the body weight and the chance of attaining an RVR in either the lower or standard ribavirin groups. A study by Loustaud-Ratti et al. demonstrated that plasma concentration of ribavirin after the first dose, expressed by ribavirin area under the concentration-time curves (AUC0–12h), was associated with RVR.10 These observations highlight the potential role of weight-based ribavirin exposure during the first 4 weeks of combination therapy on the achievement of an RVR. Because RVR is the most important single predictor of an SVR, further prospective studies are encouraged to explore the crucial dose of weight-based ribavirin exposure during first 4 weeks for achieving an RVR to maximize the treatment efficacy. Ming-Lung Yu* , Chia-Yen Dai* , Jee-Fu Huang , Wan-Long Chuang* , * 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.