Evaluation of Liver Functoin in Living Donor Liver Transplant Recipient Using Calcineurin Inhibitor Pharmacokinetics
Abstracts
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Introduction: Recovery of synthetic function following reduced size liver transplantation indicates successful regeneration of the liver lobe. Thus, albumin, liver enzymes, and prothrombin time (PT) have been used as the primary markers for monitoring living donor liver transplant recipients (LDLT-R). The detoxification function of the liver has not been utilized to monitor hepatic function, even though evidence suggests its correlation to functional liver mass. The purpose of this study was to evaluate if drug metabolism can be used as a probe to evaluate liver regeneration post-transplant. Methods: Liver enzymes, PT, tacrolimus (FK) dose, and 12 hour trough levels in 21 LDLT-R were compared with a concurrent cohort of 23 cadaveric (CAD) liver transplant recipients matched for demographics and transplant characteristics. All patients received FK, mycophenolate mofetil, and prednisone. Results: The median age of LDLT-R was 53 years with 57% male and 10% African-Americans. The estimated mean graft weight to recipient body weight ratio was 1.5% for the LDLT-R. The time to recovery of synthetic function, peak liver enzymes, and peak PT were the same for both LDLT-R and CAD. At day 7, the PT was 13.7 sec in the LDLT-R versus 13.1 sec in the CAD, p=NS. The doses of FK were significantly higher in the CAD than in the LDLT-R at 7, 14, and 28 days post-transplant, (p<0.05), but there were no differences in FK levels between the 2 groups (p=NS). By protocol, FK doses were adjusted to achieve levels of 8 to 10 ng/ml during the first month. The differences in FK doses were not observed at 3 and 6 months post-transplant and the FK levels remained stable for both CAD and LDLT-R. The median daily dose of FK increased steadily and significantly from 4mg to 6mg during the first month post-transplant to maintain target FK levels in the LDLT-R, p<0.05. This dose escalation was not observed in the CAD as both FK doses and levels remained stable. There were no differences in drug related adverse events and outcomes between the CAD and LDLT-R. Conclusions: In LDLT-R, synthetic functions recovered almost immediately, but the detoxification ability appeared to be delayed and might be correlated to the time required for the graft to regenerate. Thus, monitoring the pharmacokinetics of a drug probe may be a useful adjunct in monitoring and predicting the growth of reduced size livers undergoing regeneration. |
