Pharmacogenomics Testing in Patients with Liver Transplant and Potential Impact on Prospective Management

Abstract

Aim: Pharmacogenomics (PGx) tests are performed on whole-blood or saliva specimens. In patients with a transplanted liver, PGx results may be discordant with hepatic drug metabolizing enzyme activity. We evaluate the incidence and impact of PGx testing in liver transplant recipients, detail potential errors and describe clinical decision support (CDS) solution implemented. Materials & methods: A retrospective cohort study of liver transplant recipients at Mayo Clinic who underwent PGx testing between 1 January 1996 and 7 October 2019 were characterized. Impact of a CDS solution was evaluated. Results: There were 129 PGx tests in 117 patients. PGx testing incidence increased before (per year incidence rate ratio = 1.45, 95% CI: 1.20–1.74, p < 0.001) and after transplant (incidence rate ratio = 1.48, 95% CI: 1.27–1.72, p < 0.001). Three erroneous PGx tests were avoided 6 months following CDS implementation. Conclusion: Incidence of PGx testing in liver transplant recipients is increasing, leading to erroneous therapeutic decisions. CDS interventions and education are needed to prevent errors.

Pharmacogenomics and beyond! Customized pharmacotherapy for solid organ transplant recipients

“…Liver transplantation is an exceptional case, where pharmacogenomic data estimating liver metabolism is expected to be misleading and, therefore, is not recommended. The results of a pharmacogenomic panel performed prior to transplant would not reflect the metabolizing properties of the transplanted liver allograft, and the possible mismatch between the drug metabolizing enzymes in the upper gut and liver distort its clinical usefulness 9 . To use drug metabolizing pharmacogenomic recommendations accurately following liver transplant, the donor and recipients' pharmacogenomic profiles would need to be compared 9 .…”

“…The results of a pharmacogenomic panel performed prior to transplant would not reflect the metabolizing properties of the transplanted liver allograft, and the possible mismatch between the drug metabolizing enzymes in the upper gut and liver distort its clinical usefulness 9 . To use drug metabolizing pharmacogenomic recommendations accurately following liver transplant, the donor and recipients' pharmacogenomic profiles would need to be compared 9 . While theoretically possible, it is operationally difficult to obtain donor pharmacogenomics testing and requires ethical scrutiny 9 .…”

“…To use drug metabolizing pharmacogenomic recommendations accurately following liver transplant, the donor and recipients' pharmacogenomic profiles would need to be compared 9 . While theoretically possible, it is operationally difficult to obtain donor pharmacogenomics testing and requires ethical scrutiny 9 . Pharmacogenomics testing for extrahepatic gene‐drug interaction mechanisms (e.g., glucose‐6‐phosphate dehydrogenase enzyme expression, human leukocyte antigen genes) are expected to be reliable for interpretation post liver transplant 9 …”

“…While theoretically possible, it is operationally difficult to obtain donor pharmacogenomics testing and requires ethical scrutiny 9 . Pharmacogenomics testing for extrahepatic gene‐drug interaction mechanisms (e.g., glucose‐6‐phosphate dehydrogenase enzyme expression, human leukocyte antigen genes) are expected to be reliable for interpretation post liver transplant 9 …”

“…The ideal time to complete pharmacogenomic testing is prior to transplant, as possible DNA contaminants may be introduced from allograft tissue or blood transfusions during surgery. [6][7][8][9] Additionally, pharmacogenomic data may inform initiation of tacrolimus or azathioprine immediately after transplant. 10,11…”