HCV New Drugs

Yutaka Tsutsumi, Chie Nakayama, Koki Kamada, Ryo Kikuchi, Daiki Kudo, Shinichi Ito, Satomi Matsuoka, Souichi Shiratori, Yoshiya Yamamoto, Hirohito Naruse, Takanori Teshima

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Discussion
It was recently reported that performing antiviral therapy against HCV in the treatment of HCV-positive lymphoma has had positive effects including improvement of the lymphoma, and that antiviral therapy including interferon against low-grade lymphoma may be able to improve the prognosis when performed following chemotherapy for low-grade lymphoma [9, 10]. In our report, since HCV is often stained in tissue samples, and since cases where there is a drop in HCV viral RNA are less likely to recur [7], it is suggested that HCV is directly or indirectly associated with the occurrence and progression of lymphoma. However, the main causes of the transition to lymphoma are still unclear. Furthermore, it has been reported that improvements can be obtained with antiviral therapy alone (e.g., in cases of splenic marginal zone lymphoma), and it is expected that the use of antiviral therapy against HCV-positive lymphoma yields an improved prognosis [11, 12, 13].

On the other hand, studies of whether treatment of HCV with antiviral drugs after treatment for diffuse large-cell lymphoma contributes to the prognosis are being conducted either retrospectively or through a combination of retrospective and prospective methods [14, 15]. It has been reported that the 5-year OS and PFS can both be improved [14, 15]. Also, a report by Michot et al. pointed out the possibility of including cases where diffuse large B cell lymphoma is thought to have transformed from splenic marginal zone lymphoma [14], but in this case, cases that have transformed from splenic marginal zone lymphoma are not included. In Europe and the USA, there are many cases where splenic marginal zone lymphoma is associated with HCV. These cases are highly responsive to HCV antiviral therapy, suggesting the possibility of an improved prognosis. On the other hand, in a report by Michot et al., there were cases in which SVR could not be obtained in the antiviral therapy group, while in a report by Hosry et al., there were many cirrhosis cases among the analysis subjects, and it is thought that these factors may have acted on OS and PFS in a negative direction [14, 15]. In our analysis, genotype 2 was more common in the DAA group, while genotype 1 was more common in the control 1 group, and the difference in genotype may also have affected the outcome of treatment. It is thought that this affected the OS and PFS analysis of this report and earlier reports [14, 15].

Since DAA was used after obtaining confirmation of chronic HCV-positive hepatitis by liver biopsy in the cases analyzed here, DAA therapy was performed about 6 weeks after treatment with anticancer drugs. However, there are no clear guidelines on the appropriate timing for DAA treatment, such as whether antiviral therapy should be performed after or during lymphoma treatment, or before anticancer treatment of the lymphoma. A recent report investigated the interactions of DAA administered simultaneously with various anticancer drugs in cancer cases complicated by HCV infection. In this report, although blood toxicity and gastrointestinal toxicity were found, the change brought about by DAA therapy was only 10%, and the SVR was also 95%, and it was reported that it may be possible to use DAA therapy simultaneously with anticancer treatment [16, 17]. On the other hand, in this analysis, there were no problems arising from the continued use of DAA therapy, or complications requiring a change of medication regime, but this could be because there were no cases where DAA therapy was performed at the same time as the anticancer treatment.

In this study, we are conducting a prospective examination of five cases, and so far, 2 years has elapsed since the start of treatment, but in all five cases, the patients have survived without any recurrence, and it seems that following chemotherapy with antiviral therapy may contribute to the prognosis in cases of HCV-positive diffuse large-cell lymphoma. Furthermore, although analysis has only been performed in a few cases, it seems that HCV-RNA-positive cases may have a poorer prognosis than non-HCV-infected diffuse large-cell lymphoma cases, and although there are signs that the prognosis is improved for DAA treatment cases, it may be recommended that DAA treatment is performed after remission in HCV-RNA-positive diffuse large-cell lymphoma. However, since we have only examined a few cases for a short period of time, we are hopeful that the usefulness of antiHCV therapy will be demonstrated more clearly by a prospective study involving a larger number of people.

https://link.springer.com/article/10.1007%2Fs00277-017-3129-0