الفهرس 
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Abstract
L
iver transplantation (LT) is currently recognized as the most effective treatment for all types of end stage liver diseases. Major advances have been made in the field of liver transplantation due to improvements in surgical techniques and organ conservation as well as optimization of intensive care and immunosuppressive management.
Immunosuppressant is mandatory for the prevention and treatment of graft rejection. The appropriate choice and use of immunosuppressant is directly related to the survival of liver transplant recipients.
Immunosuppressive agents are required in liver transplantation for induction of immunosuppression in the early phase, maintenance of immunosuppression in the late phase or for the treatment of graft rejection.
FK506 (tacrolimus) is a powerful and selective anti-T-lymphocyte agent, with a mechanism of action similar to that of cyclosporine, it binds to an intracellular receptor and subsequently binds to calcineurin and inhibits the calcineurin pathway that stimulate the transcription factor Nuclear factor of activated T cells (NFAT). Dephosphorylated NF-AT translocate to the nucleus, where it binds to specific DNA sites in the promoter regions of several cytokine genes, including interleukin (IL)-2. Through this series of actions, tacrolimus inhibit transcription of IL-2 thus inhibit proliferation and differentiation of T cells producing immunosuppression.
Gene polymorphism (6986A>G) in cytochrome P450 3A5 (CYP 3A5) is assumed to be the major factor that contributes to the pharmacokinetic variability of tacrolimus. The presence of an A allele at the polymorphic site in the CYP3A5 gene suggests that an individual has a functionally active enzyme (expresser) and carries one of the two genotypes (CYP 3A5*1*1 or CYP 3A5*1*3). By contrast, non-expressers do not have a functionally active enzyme and carry the CYP3A5 3*3 genotype. This finding suggests that CYP3A5*1 carriers are at higher risk of under‐immunosuppression and may require higher doses of the drug.
We aimed at our study to correlate CYP3A5 single nucleotide polymorphisms (SNP) rs776746 and its effect on tacrolimus dose requirements and trough levels in Egyptian liver transplant recipients.
The study included 25 liver transplant recipients and their respective donors. All subjects of this study were subjected to full medical history, clinical evaluation, laboratory investigations, and CYP3A5 gene polymorphism. Tacrolimus trough level was evaluated for all the recipients during the first 3 months post transplantation.
The present study revealed statistical significance of 3*1 & 1*1 genotypes of the donors when correlated to the effect on tacrolimus C/D ratio and weight adjusted tacrolimus dose during the first month post transplantation but not during 2nd and 3rd months. Subjects carrying 3*1 & 1*1 genotypes required higher doses of tacrolimus to achieve the desired trough levels compared to subjects carrying 3*3 genotype.
In conclusion, the present study revealed presence of significant association between CYP3A5 genotype of the donors of liver transplantation and tacrolimus required dose and trough levels.