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.