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अमूर्त

Ischemic-Type Biliary Lesions (ITBLs) after Liver Transplantation is associated with High Expression of CYP3A5 rs776746 Allele A and the Immunilogical Therapeutic Mechanisms of Medicine

Chuan-Yun Li, Dong-Dong Lin, Dao-Bing Zeng, Qing-Liang Guo, Ju-Shan Wu, Ning Li and Shi-Chun Lu

Ischemic-Type Biliary Lesions (ITBLs) are a common and difficult to treat biliary complication associated with liver transplantation. It is one of the main factors impacting long-term recipient and graft survival. It is therefore important and meaningful to investigate the mechanisms, effective prevention, and treatment of ITBLs. In this study, we retrospectively reviewed the records of 32 post-liver transplant patients with ITBLs, which were divided into those who received rapamycin and those who did not (controls). Using an All Prep DNA/RNA Mini Kit (Qiagen, Germany) according to the manufacturer’s instructions, single nucleotide polymorphism (SNP) of cytochrome P450, family 3, subfamily A5 (CYP3A5) rs776746 were genotyped in both donors and recipients. There are 15 cases have one alleles A, 12 cases two alleles A and 5 cases three alleles A in both donors and recipients. With increasing numbers of CYP3A5 rs776746 alleles A, patients were found to have increasingly higher bile duct injury score at time points when ITBLs were identified. After rapamycin treatment, there was a significant improvement in liver function indexes, and the bile duct immunopathological damage alleviated significantly. These findings demonstrate that (i) Ischemic- Type Biliary Lesions (ITBLs) after liver transplantation is associated with high expression of CYP3A5 rs776746 allele A; and (ii) Rapamycin can stimulating FoxP3+ Treg cells, suppressing immunopathological damage, and promoting epithelial repair in bile ducts.