We read with great interest the article in a recent issue of HEPATOLOGY by Diago et al.,1 who reported that the overall sustained virologic response (SVR) rate to peginterferon alfa-2a (40KD) (PEGIFN) plus ribavirin among patients infected with hepatitis C virus genotype 2/3 (HCV-2/3) was significantly higher in patients randomized to 24 weeks, rather than 16 weeks, of treatment (91% versus 82%; P = 0.0006) and among patients infected with genotype 2 (92% versus 81%; P = 0.001) but not genotype 3 (90% versus 84%; P = 0.13). In particular, the SVR rates in patients with a viral load ≤400,000 IU/mL randomized to 24 and 16 weeks of treatment were similar (95% versus 91%; P = 0.20). Assignment to 24 weeks of treatment, absence of advanced fibrosis on liver biopsy, lower HCV RNA level, and lower body weight were significant pretreatment predictors of SVR. The authors concluded the standard 24-week regimen of PEGIFN/ribavirin is significantly more effective than an abbreviated 16-week regimen in genotype 2/3 patients who achieve a rapid virologic response (RVR) (HCV RNA < 50 IU/mL at week 4). Abbreviated regimens may be considered in patients with a low baseline viral load who achieve an RVR.
The present study, which uses ribavirin 800 mg/day, showed RVR rates of 65.9% (863 of 1309 patients) in patients with HCV-2/3, which was similar to 62% reported by Lagging et al.2 Our previous results from a randomized controlled trial of Taiwanese patients with HCV-2 showed that an RVR was achieved by 86.7% of patients3 which seemed higher than the 64%-75.0% RVR rate for patients with HCV-2 in western countries.4-6 The higher RVR rate in Taiwanese patients may be due to a higher initial dose of ribavirin per body weight (BW) (15.5 mg/kg/day) which makes the possibly “suboptimal” initial doses of ribavirin noteworthy.7
With higher initial dose of ribavirin per BW, the SVR rates in response to short-term treatment (12-16 weeks) in patients with HCV-2 with RVR were 89%-95% in studies by Dalgard et al., Mangia et al., and Andriulli et al.,4, 5, 8, 9 which were similar to the 92% SVR rate with 24 weeks treatment by Diago et al. In Taiwanese patients with HCV-2 who had RVR, we have shown that the very high SVR rates to 16 weeks and 24 weeks of PEGIFN treatment with weight-based ribavirin at a dose of 1000-1200 mg/day were comparable (100% versus 98%, respectively).3 For SVR, Di Martino et al. reported in their meta-analysis study that shorter-duration therapy with fixed-dose 800 mg/day ribavirin yielded a lower SVR rate than 24 weeks of treatment, and a weight-based ribavirin regimen for a 16-week course of therapy seemed to achieve equivalent effect as a 24-week treatment duration with fixed-dose 800 mg/day ribavirin.10 Diago et al. have reported SVR rates of 92% and 81% in patients with HCV-2 who were treated with PEGIFN and ribavirin 800 mg/day for 24 weeks and 16 weeks, respectively.1 Ferenci et al. have shown the lower rates of SVR in patients with HCV-2 who were treated with lower initiation doses (77.8% and 55.6% with ribavirin 800 mg/day and 400 mg/day for 24 weeks, respectively).11 In addition, the lower BW was an independent predictor of SVR by Diago et al. which might further suggest the importance of the weight-based dose of ribavirin. Taken together, a better SVR rate can be achieved when patients with HCV-2 are treated by regimens with higher initial dose of ribavirin per BW, even with shortened duration of therapy in HCV-2 patients who achieve an RVR.
Diago et al. also showed the role of lower HCV RNA level on the SVR in patients infected with HCV-2/3.1 Our previous randomized trial for HCV-1 patients has shown that HCV RNA level, in addition to an RVR and mean weight-based exposure of ribavirin, was the significant predictor for SVR; patients with RVR and low HCV RNA level achieved similar SVR rates after 24 or 48 weeks of PEGIFN/ribavirin therapy (96% and 100%, respectively).12 However, in patients with HCV-2 with RVR and a higher initial dose of ribavirin per BW, the HCV RNA level played a minimal role on the SVR rate and, in addition, the similar SVR rates between shortened (12-16 weeks) and standard (24 weeks) duration of therapy were observed in our study (100% versus 98%)3 and in reports by Mangia et al. (87% versus 89%)4 and Dalgard et al. (93% versus 97%).5 In patients with HCV-2 who had RVR, the weight-based ribavirin regimen seemed to be able to ameliorate the deteriorated efficacy of shortened duration and covered the role of HCV RNA level. Further large-scale studies to confirm the critical role of weight-based dosing of ribavirin in abbreviated regimens for patients with HCV-2/3 who achieve RVR are necessary.