Switch of immunosuppressant therapy from tacrolimus to cyclosporine in 30 liver transplant patients who developed hyperbilirubinemia

In this study, we summarized the efficacy of switching the immunosuppressant treatment for liver transplant patients with hyperbilirubinemia from tacrolimus to cyclosporine and outlined how pharmacogenetics could guide the application and interchangeability of immunosuppressants. We retrospectively reviewed the results of switching immunosuppressant therapy with tacrolimus to that with cyclosporine in patients who developed hyperbilirubinemia after liver transplantation. The method of switching and its effects, and postoperative analysis of the optimal immunosuppressant selection based on the CYP3A5 genotype are discussed. In a group of 245 liver transplant patients, the main immunosuppressant treatment was switched from tacrolimus to cyclosporine for 30 patients. The reason for the switch was the development of hyperbilirubinemia without biliary complications in those patients. The decrease in bilirubin levels was not significant after an increase in the tacrolimus dosage. The method of switching included discontinuation of tacrolimus administration for 24 h before cyclosporine was infused at a dose of 100-150 mg twice daily. The rest of the conventional immunosuppressant therapy remained unchanged. After the switch, total bilirubin levels in these patients began to decline within 2 weeks. Follow-up examinations six months later revealed that patients did not experience any significant renal damage. We noted that in all 30 cases, either the donor or recipient (or both) had CYP3A5 genotype AG or AA. The predominance of these genotypes was significantly different from the distribution of donor/recipient genotype combinations in the overall group of liver transplant patients. The widely used tacrolimus-based immunosuppressant treatment after liver transplantation may not be ideal in cases when either the donor or recipient have CYP3A5 genotype AG or AA. Clinical manifestations in such patients treated with tacrolimus may include persistent hyperbilirubinemia without biliary complications. Therefore, based on the CYP3A5 genotype for this particular patient population, a switch in the prescribed immunosuppressant may be warranted in order to prevent the development of hyperbilirubinemia and to reduce the adverse effects of tacrolimus.