Discussion:
In this study, we constructed a nomogram to predict the risk of poor curative effects of those recipients who receive an IS protocol based on TAC. ROC curve, calibration curve and DCA were employed to identify the model’s predicted reliability, which showed a well prediction ability with AUC values over 0.7. The nomogram showed that recipients with CYP type of AA or AG, low serum level of albumin, high GRWR and not receiving volume reduction had a significant higher risk of switching IS drugs. Donor CYP type of AA or AG also contributed medium points to this model. No cholangitis and spleen long diameter above 86 cm did not make much contribution.
Recipients who express CYP3A5 are more difficult to reach the target blood concentration of TAC than those not[14], which may increase the risk of toxicity of TAC because of overexposure. Similar to this, both recipient and donor CYP type are predictors in our model. However, it seems that recipient CYP type has no correlation with the oral clearance of TAC[15] as it mainly metabolizes in the donor liver and intestine[16]. The relationship between recipient CYP type and TAC dosing are still not clearly defined in pediatric liver transplantation[17]. Research showed that recipient CYP type has no significant contribution on metabolism of TAC[18] while other authors found that recipient CYP type plays a more prominent role than donor CYP type[19]. The discrepancy may be due to the expression of CYP are associate with the length of time after pediatric LT and recipient age[20, 21].
The patients who were initially treated with TAC but later switched to CsA had a higher rate of acute rejection, urinary complications and mental and neurological complications, which was quite possible that severe complications were the reason to consider switching TAC to CsA. Lower mortality and incidence of portal vein complications and PTLD may indicate that this part of recipients benefited from the protocol of switching IS drugs. To achieve individual therapy for minimizing the side effect of IS drugs, CsA is an alternative when TAC-based therapy receiving a poor prognosis.
The inherent limitations of a single-center retrospective study are the limitations in our study. The definite reason clinicians chose a therapeutic regimen of switching IS drugs for each recipient is not available now. Additionally, a small part of the recipient had switched CsA to TAC latterly and did not report in our study. More prospective studies are required to validate the nomogram.
In conclusion, some recipients may benefit from switching IS drugs timely after pediatric LT. We constructed a simple model including recipient CYP type, cholangitis before LT, GRWR, spleen long diameter, serum albumin, graft volume reduction and donor CYP type to predict the risk of poor curative effects of those recipients who receive an IS protocol based on TAC. The nomogram can help clinicians quickly choose CsA as an alternative if there are high risks.