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Graft-Versus-Host Disease

Efficacy of bezafibrate for chronic GVHD of the liver after allogeneic hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 45, pages 912–918 (2010)Cite this article

Abstract

Chronic GVHD (cGVHD) of the liver is an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-SCT). It is characterized by the destruction of bile duct epithelium followed by progressive cholestasis, which resembles primary biliary cirrhosis (PBC) clinically and histologically. Bezafibrate (BF) is a widely used agent for hyperlipidemia that is also effective in ursodeoxycholic acid (UDCA)-resistant PBC patients. The putative mechanism in cholestasis is that BF upregulates the expression of phosphatidylcholine flippase on bile canaliculi, facilitates phospholipid output into bile and relieves bile duct damage caused by hydrophobic bile salts. Therefore, the effects of BF in patients with cGVHD of the liver were investigated. Of 87 patients with cGVHD who survived more than 100 days after SCT, 8 were given BF to treat liver cGVHD because of a poor therapeutic response to UDCA and immunosuppressants. The serum alkaline phosphatase (ALP) and γ-glutamyl transpeptidase (γ-GTP) levels decreased significantly within 1 month after initiation of BF therapy compared with those before BF therapy in all patients (ALP, 964.9.0±306.9 to 597.8±102.5 IU/l, P=0.012; γ-GTP, 528.8±299.0 to 269.0±119.9 IU/l, P=0.012). BF was effective in patients with liver cGVHD, including UDCA-resistant patients. BF could be a novel therapeutic option for liver cGVHD that helps to preserve normal immunity with the antileukemic effect of cGVHD.

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Acknowledgements

This work was supported in part by Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sport, Science and Technology, and for Cancer Research from the Japanese Ministry of Health, Labor and Welfare.

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Authors and Affiliations

  1. Department of Internal Medicine, National Hospital Organization, Kumamoto Medical Center, Kumamoto, Japan

    M Hidaka, T Matsui, T Kawakita, Y Inoue, T Sakai, N Harada, S Takemoto, S Nagakura, T Kiyokawa & F Kawano

  2. Department of Gastroenterology and Hepatology, Kochi Medical School, Nankoku, Kochi, Japan

    S Iwasaki, M Takahashi, T Saibara & S Onishi

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  1. M Hidaka
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Correspondence to M Hidaka.

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Hidaka, M., Iwasaki, S., Matsui, T. et al. Efficacy of bezafibrate for chronic GVHD of the liver after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 45, 912–918 (2010). https://doi.org/10.1038/bmt.2009.251

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