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

• Published in: Bone marrow transplantation (Basingstoke) Vol. 45; no. 5; pp. 912 - 918
• Main Authors: Hidaka, M, Iwasaki, S, Matsui, T, Kawakita, T, Inoue, Y, Sakai, T, Harada, N, Takemoto, S, Nagakura, S, Kiyokawa, T, Takahashi, M, Saibara, T, Onishi, S, Kawano, F
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-05-2010; Nature Publishing Group
• Subjects: Acid resistance; Adult; Alkaline phosphatase; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Anticancer properties; Antilipemic agents; Bezafibrate; Bezafibrate - therapeutic use; Bile ducts; Biological and medical sciences; Bone marrow; Bone marrow, stem cells transplantation. Graft versus host reaction; Cell Biology; Cholestasis; Chronic Disease; Cirrhosis; Complications and side effects; Dosage and administration; Drug therapy; Epithelium; Female; Gallbladder diseases; Graft versus host reaction; Graft vs Host Disease - complications; Graft vs Host Disease - diagnosis; Graft vs Host Disease - therapy; Hematology; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic stem cells; Humans; Hydrophobicity; Hyperlipidemia; Immunosuppressive agents; Internal Medicine; Lecithin; Leukemia; Liver; Liver cirrhosis; Liver Diseases - complications; Liver Diseases - diagnosis; Liver Diseases - therapy; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Morbidity; original-article; Patient outcomes; Phosphatidylcholine; Phospholipids; Primary biliary cirrhosis; Public Health; Retrospective Studies; Risk factors; Salts; Stem cell transplantation; Stem Cells; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Transplantation, Homologous; Ursodeoxycholic acid; γ-Glutamyltransferase; Japan; PBC; bezafibrate; cGVHD; UDCA; allo-SCT; Immunopathology; Graft versus host disease; Hematology; Digestive system; Fibrate derivatives; Stem cell; Treatment efficiency; Liver; Hematopoietic cell; Homograft; Chronic; Allogeneic hematopoietic stem cell transplantation; Bezafibrate; Graft; Antilipemic agent
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/bmt.2009.251

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.