The purpose of the project is to improve outcomes of liver transplantation among African Americans by conducting clinical and biochemical investigations. The project includes several components whose findings will be studied individually and in conjunction with each other to determine optimally effective therapies an protocols. Clinical investigations will involve immunosuppression, infection control, and non-heart-beating donors.
The specific aims of the clinical components are to answer: (1) How can immunosuppression in African American transplant patients be optimized without increases in infection rates? (2) Can infection after transplantation be controlled in African American liver recipients? and (3) Are livers from non-heart-beating donors suitable for transplantation? Clinical investigations of immunosuppression will involve assessment of the effects of cyclosporine, OKT3, and FK506. Infection control will focus on cytomegalovirus. The clinical investigations also will explore the potential of non-heart-beating donors in increasing the supply of livers for transplantation. Biochemical investigations will focus on genetics, pharmacokinetics, and measures of liver function.
The specific aims of the biochemical investigation are to answer: (1) Can genetics tests predict the amount of FK-506 and cyclosporine that should be administered to African American liver recipients? (2) How can the immunosuppressive properties of FK-506 and cyclosporine be optimized? and (3) Can assessment of liver status be improved to facilitate clinical decision making? One portion of the biochemical studies will gather data on dosage of FK-506 and cyclosporine in conjunction with other drugs by examining the role of genetics in the activity of cytochrome P450 IIIA4. The pharmacokinetics of FK-506 and cyclosporine will be investigated by determining how metabolites and diet influence the drugs immunosuppressive properties. Assessment of in vivo liver status will be conducted by measuring cytochrome oxidase activity and hepatic blood flow.
