Cytochrome P450 in living donor liver transplantation

Abstract

Cytochrome P450 metabolizes many drugs in the liver. Three genotypes of CYP2C19 with extensive, intermediate, and poor metabolizing activity, respectively, have been identified in peripheral blood of transplant recipients and new liver grafts in living donor liver transplantation (LDLT). The expression of the final genotype in liver graft biopsies depends on the donor, whereas the expression in peripheral blood mononuclear cells depends on the recipient. The metabolizing isoenzyme of the major anti-rejection agents passes through CYP3A4, CYP3A5 and MDR1, which have also been identified to have similar biological characteristics as genotype of CYP2C19 in liver tissue. Recently, pyrosequencing has been used to investigate the expressions of different genotypes in liver grafts in LDLT. This review focuses on recent findings regarding the biological expressions of the CYP2C19, CYP3A4, CYP3A5 and MRD1 genotypes in liver grafts before and after LDLT. The application of pyrosequencing may be beneficial in further research on liver transplantation. Laser capture microdissection of hepatocytes in liver grafts may be a direction for future research.

Identification of IL-28B Genotype Modification in Hepatocytes after Living Donor Liver Transplantation by Laser Capture Microdissection and Pyrosequencing Analysis

“…This is an exciting discovery with regard to the treatment responses of recipients with HCV infection after liver transplantation. In our previous study on the cytochrome P450 system, a similar phenomenon was observed with modified SNPs genotypes in CYP2C19, CYP3A4, CYP3A5, and MDR1-3435, when the genotypes of the donor allograft and the recipients were different [14]. Our results suggest that the recipient's liver mutated to a favourable IL-28B genotype such as rs8099917…”

Genetic polymorphisms of the hepatic pathways of fatty liver disease after living donor liver transplantation

“…In fact, graft rejection and biliary complication as cholangitis contribute to acute liver injury at the early phase after LDLT. Immunosuppressive drugs are used to control the issue of graft rejection by cytochrome P450 system with CYP3A4 and CYP3A5 . CYP27A1 and CYP3A4 in P450 system should be much complicated impact for the FLD after LDLT .…”

“…According to our previous studies on new liver grafts, the cytochrome P450 system was one of the most important systems affecting clinical outcomes in recipients after living donor liver transplantation (LDLT) . In the vitamin D synthetic pathway, CYP27A1 and vitamin D receptor (VDR) are expressed in the liver, and CYP27B1 catalyses the production of 1,25‐dihydroxyvitamin D in the kidney …”

Effects of Shu Gan Jian Pi formula on rats with carbon tetrachloride-induced liver fibrosis using serum metabonomics based on gas chromatography-time of flight mass spectrometry

“…Glycine is combined with benzoic acid to form hippuric acid under cytochrome P450 catalysis. Cytochrome P450 activity is associated with the development of liver fibrosis ( 51 ). The SGJPF group exhibited lower hippuric acid levels compared with those of the model group.…”