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Mycophenolate mofetil may induce prolonged severe anemia during pegylated-interferon/ribavirin/simeprevir therapy in liver transplant recipients

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Abstract

Aim: Pegylated-interferon/ribavirin/simeprevir (PEG-IFN/RBV/SMV) combination therapy is widely used for hepatitis C virus (HCV) treatment after liver transplantation (LT). Here, we observed two cases of extended severe anemia during PEG-IFN/RBV/SMV therapy for HCV serological type 1 re-infected after LT. Immunosuppressants consisted of tacrolimus and mycophenolate mofetil (MMF). Case 1 was a 65-year-old-woman treated with PEG-IFN/RBV/SMV therapy and 500 mg MMF/day 9 months after LT. Her serum hemoglobin (Hb) level decreased from 10 to 8.4 mg/dL on day 25. Despite discontinuing the PEG-IFN/RBV/SMV treatment on day 32, her Hb level decreased to 5.1 mg/dL on day 40. Case 2 was a 61-year-old-woman started on PEG-IFN/RBV/SMV therapy 20 months after LT. Her serum Hb level decreased from 12.2 to 7.1 mg/dL on day 39. The MMF dose was reduced from 1,500 to 1,000 mg/day, and her Hb level was maintained. Red blood cell transfusions were required in both cases, and anemia persisted for 2 months. These patients had the C/C major type inosine triphosphatase (ITPA) polymorphism. In conclusion, MMF induced severe persistent anemia by co-treatment with IFN/RBV in patients who underwent LT. Thus, the immunosuppressant dose should be chosen carefully for patients with the high-risk ITPA allele.

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Acknowledgments

This study was supported by the Takako Satake Award at TWMU and a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology, Japan (#26461024-0001) to T.K.

Disclosures

Conflict of Interest: Tomomi Kogiso, Katsutoshi Tokushige, Etsuko Hashimoto, Makiko Taniai, Akiko Omori, Yoshihito Kotera, Hiroto Egawa, Masakazu Yamamoto,and Keiko Shiratori declare that they have no conflict of interest.

Human/Animal Rights: All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008(5).

Informed Consent: Informed consent was obtained from all patients for being included in the study.

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Correspondence to Tomomi Kogiso.

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Kogiso, T., Tokushige, K., Hashimoto, E. et al. Mycophenolate mofetil may induce prolonged severe anemia during pegylated-interferon/ribavirin/simeprevir therapy in liver transplant recipients. Clin J Gastroenterol 8, 156–161 (2015). https://doi.org/10.1007/s12328-015-0570-2

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