The present study showed that Japanese patients with HCV genotype 2 and undetectable HCV-RNA at week 4 of treatment achieved a high SVR rate with PEG-IFN monotherapy for 24 weeks or less. In Japan, between December 2003 and March 2007, until the national health insurance system approved the combination therapy PEG-IFN-alfa-2a with RBV, PEG-IFN-alfa-2a monotherapy was used at 180 μg once a week for 24-48 weeks for the treatment of chronic hepatitis C. Even now, we cannot use the combination therapy for HCV genotype 2 treatment-naïve patients with low viral loads under the national health insurance system in our country. Then, we used 180 μg of PEG-IFN-alfa-2a monotherapies for chronic hepatitis C patients and retrospectively analyzed the data during this period in the present study. This study was not a controlled trial, and various durations of treatment were adopted for the respective patients. However, the SVR rate of 100% in patients with low viral load and 17.1 weeks as average treatment duration and that of 84.2% in those with high viral load and undetectable HCV-RNA at week 4 of average treatment duration of 24 weeks were very high. Therefore, 24 weeks of PEG-IFN therapy could represent a sufficient treatment duration for selected patients with HCV genotype 2 and undetectable HCV-RNA at week 4 of treatment.
Since IFN treatment, including PEG-IFN, can cause medical conditions such as depression, interstitial pneumonia, diabetes mellitus, thyroid disease, leukopenia, thrombocytopenia and flu-like symptoms, its duration should preferably be minimal . Therefore, to minimize the possibility of such side effects, and additionally, in consideration of the cost of IFN treatment, reducing the length of treatment is desirable [22, 23]. The combination therapy with PEG-IFN and RBV for 24 weeks has been shown to be more effective, and it has become the present standard care . However, in some cases, and especially in older patients, RBV cannot be administered because of possible side effects, including severe anemia. As patients tend to be older in Japan than in Western countries, more therapeutic options are needed.
Recently, there have been several reports about the importance of interleukin-28B (IL28B) SNP in the prediction of SVR in HCV genotype 2-patients treated with PEG-IFN-alfa plus RBV therapy [20, 24–28]. IL28B SNP rs8099917 was determined in 11 HCV genotype 2-patients treated with IFN monotherapy, revealing that 5 and 6, respectively, had major (TT) and minor (TG and GG) phenotypes and that 2 null-responders had TG phenotypes, and 4 had relapsed and 5 had SVR [, data not shown]. It is possible that IL28B SNP could improve the SVR rate in non-RVR patients and non-responder patients by changing monotherapy to combination therapy , but further studies will be needed.
Recently, there have been reports that in HCV genotype 2/3-infected patients with a very rapid viral response (vRVR), i.e. HCV RNA below 1,000 IU/mL on day 7, the combination PEG-IFN plus RBV treatment could be shortened to 12-16 weeks if no dose reduction had been made . Further studies will be needed to reveal how long patients obtaining RVR should be treated. Our study indicates that PEG-IFN monotherapy for 24 weeks or less is sufficient to treat patients with HCV genotype 2, especially those who become negative for HCV RNA by week 4 of treatment. On the other hand, RBV combination therapy should be considered in those whose HCV RNA becomes seropositive by week 4 of treatment. Our results need to be confirmed by a randomized control study as soon as possible. Our previous studies showed that the overall SVR rate of HCV genotype 2-patients treated with PEG-IFN-alfa-2b plus RBV for 16-48 weeks was 82.6% , and the SVR rate of combination treatments for some patients infected with HCV genotype 2 was superior to that of PEG-IFN-alfa-2a monotherapy (75.5%) in the present study. Although our retrospective study had a rather small sample size with various treatment durations, our results may provide support to the future design of personalized therapy for HCV genotype 2-patients in certain situations where they cannot be treated with RBV.