In this study, we showed that a shorter course of 16‐week peginterferon and weight‐based ribavirin 1000–1200 mg/day is as effective as a standard 24‐week course in Taiwanese patients infected with chronic HCV2 who achieved RVR at week 4. Achievement of RVR at week 4 and patient's age, but not treatment duration, were independent factors associated with SVR. The shorter duration of treatment resulted in a lower incidence of adverse events such as alopecia and in lower cost of treatment. An insufficient dose of ribavirin after 4 weeks of treatment may compromise the response to a 16‐week treatment in patients without RVR at week 4.
For patients infected with HCV2, peginterferon/ribavirin for 24 weeks is the standard recommended treatment,5
which could achieve SVR rates similar to those treated with a 48‐week course.8
Subsequently, three European studies13,14,15
have shown that a shorter course of treatment over 12–16 weeks with peginterferon/ribavirin is as effective as a 24‐week course for patients with HCV2 with RVR at 4 weeks. These previous studies used RVR at week 4 as an indicator for choosing the treatment period. Only patients who had RVR were assigned to groups that had shorter treatment periods.13,14,15
Thus, no data were available for shorter courses of treatment in patients who did not achieve RVR. In our study, Taiwanese patients with chronic HCV2 infection were randomly assigned to either 16 or 24 weeks of treatment with peginterferon/ribavirin regardless of their RVR. Our results clearly showed that a rapid response at week 4 is an important factor that can significantly affect the outcome of treatment in both the 16‐week and 24‐week groups. Consistent with previous European studies,13,14,15
this study also showed that 16 and 24 weeks of peginterferon/ribavirin treatment provided equal efficacy for patients with HCV2 who achieved RVR at week 4, with an SVR rate of 98–100%. Recent data also suggest that 24 weeks of treatment is effective and sufficient for achieving SVR in patients with HCV1 or HCV4 who exhibit RVR at 4 weeks, compared with a recommended standard course of 48 weeks of treatment.22,23,24
These findings emphasise the importance of RVR at 4 weeks in the individualised treatment for CHC.
Other studies examining shorter treatment durations in patients with HCV2 and HCV3 have shown higher relapse rates with the shorter treatment duration.14,15
We also observed that the 16‐week group had a lower SVR rate and a higher relapse rate than the 24‐week group for patients who did not achieve RVR. However, too few patients had a relapse for this to be a meaningful comparison. The between‐group difference showed a tendency towards ribavirin dose reduction with a higher relapse rate and lower SVR rate. We also found that a significantly lower mean dose of ribavirin by body weight after 4 weeks of treatment was observed in non‐responders who did not achieve RVR at week 4 after 16 weeks treatment, even with a limited number of cases. Significant incremental virological response rates with adherence were not detected for patients with HCV2 or HCV3 with 24 or 48 weeks of treatment.12
Our observation suggested that ribavirin adherence and ribavirin dose by body weight after 4 weeks of treatment may play a role in the response to a shorter course of treatment for patients with HCV2 without RVR at week 4. Further large‐scale studies are needed to confirm these findings.
For patients without RVR, a 16‐week regimen is obviously suboptimum. Nevertheless, the efficacy remains unsatisfactory in this relatively difficult‐to‐treat subgroup even with a 24‐week course of treatment (SVR rate 77% in this study and 50–72% in European studies13,14
). Whether an extended course of treatment >24 weeks is of benefit for this subgroup remains to be studied.
The SVR rate of patients with HCV2 with RVR at 4 weeks using a shorter course of peginterferon and ribavirin is slightly higher in our study than observed in previous studies conducted in Europe.13,14,15,25
A greater response to peginterferon/ribavirin in Taiwanese patients with chronic HCV‐1b than in Caucasian patients was also observed in previous studies.26,27
There may be a few reasons for this diffference. Firstly, racial factors have been shown to influence the virological response even when peginterferon/ribavirin are given for the standard duration of treatment.16,17
Ethnic and racial differences in immunogenetics, peginterferon pharmacokinetics, signal transduction pathway or viral kinetics may play a role in determining the outcome of HCV infections.3,28,29
Secondly, geographical variations of HCV by the emergence of quasispecies may have influenced the virological response.30
Thirdly, the mean body weight was lower in our study population than in previous European populations, with a mean difference of 3–10 kg. The higher average doses of peginterferon or ribavirin per kilogram body weight in our patients might contribute to a higher SVR.31,32
Previous study showed that peginterferon and ribavirin at a dose of 800 mg/day is as effective as peginterferon and ribavirin at a dose of 1000–1200 mg/day in patients with HCV2 or HCV3 infections with a 24‐week regimen.33
Thus, peginterferon and ribavirin at a dose of 800 mg/day for 24 weeks is recommended for patients with HCV2 or HCV3.6
In our study we used a higher ribavirin dose of 1000–1200 mg/day to lower the relapse rate in patients treated for 16 weeks. More recently, the ACCELERATE Trial, evaluating 16 or 24 weeks of peginterferon α‐2a 180 μg/week and ribavirin 800 mg/day for patients with HCV2 and HCV3 with quantifiable serum HCV RNA (>600 IU/ml), showed that SVR was significantly greater with 24 rather than 16 weeks of treatment for patients with HCV2 (82% vs 65%; p<0.001).25
In the ACCELERATE Trial, the mean body weight of patients with HCV2 was around 84 kg, with a mean ribavirin dose of 9.52 mg/kg/day for a daily dose of 800 mg, in contrast to 15.3 mg/kg/day in our study. The difference may explain the conflict in the results between the ACCELERATE Trial and this study. Whether a higher weight‐based dose of ribavirin is required for a shorter duration of treatment without compromising the efficacy for treating patients with HCV2 through the reduction of the relapse rate remains to be studied.
A shorter treatment period can benefit patients by reducing the cost of treatment and the incidence of adverse events.14
As the mean doses of peginterferon and ribavirin were not different between the groups in our study, the reduced incidence of adverse events can be considered to be a benefit of shorter treatment duration. Shorter treatment duration can, in particular, reduce the incidence of delayed side effects of peginterferon treatment. In our study, the incidence of alopecia, a common late side effect of peginterferon,34
was significantly less in the short‐duration treatment group.
In conclusion, this study shows that for patients with CHC infected with HCV2 who achieved RVR at 4 weeks, the efficacy of peginterferon α‐2a and weight‐based ribavirin at a dose of 1000–1200 mg/day administered for 16 weeks is comparable with treatment duration of 24 weeks. A shorter duration of treatment can reduce the incidence of adverse events and the cost of treatment. Our results provide information necessary for decision making of individualised treatment based on response at 4 weeks in CHC patients with HCV2 infections.