Immunosuppression for older liver transplant recipients

被引:6
作者
De Simone, Paolo [1 ,2 ]
Battistella, Sara [3 ]
Lai, Quirino [4 ]
Ducci, Juri [1 ]
D'Arcangelo, Francesca [3 ]
Marchetti, Piero [5 ]
Russo, Francesco Paolo [3 ]
Burra, Patrizia [3 ]
机构
[1] Univ Pisa Med Sch Hosp, Liver Transplant Program, Pisa, Italy
[2] Univ Pisa, Dept Surg Med Biochem Pathol & Intens Care, Pisa, Italy
[3] Padua Univ Hosp, Dept Surg, Gastroenterol Multivisceral Transplant Unit Oncol, Padua, Italy
[4] Univ Roma La Sapienza, Gen Surg & Organ Transplantat Unit, Rome, Italy
[5] Univ Pisa, Diabetol Unit, Med Sch Hosp, Pisa, Italy
关键词
Liver transplantation; Aging; Immunosuppression; Complications; Outcome; LONGITUDINAL PHARMACOKINETICS; CLINICAL PHARMACOKINETICS; MYCOPHENOLATE-MOFETIL; MACHINE PERFUSION; INDUCTION THERAPY; DRUG-METABOLISM; ACUTE REJECTION; P-GLYCOPROTEIN; AGE; YOUNGER;
D O I
10.1016/j.trre.2023.100817
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Older liver transplant recipients have a lower risk of acute rejection than younger patients (9% for patients aged >= 65 years versus 23% for those aged 18-34 years) and are more vulnerable to immunosuppression-related complications. The number of liver transplant recipients >= 65 years has risen to 22% in Europe and the US, but limited information is available on the optimal immunosuppressive regimen for these patients. In this review, we discuss the appropriate management of immunosuppressive agents in older adults to minimize adverse events while avoiding acute rejection. The way the body processes drugs greatly depends on age. In the case of calcineurin inhibitor drugs, aging reduces hepatic metabolism, leading to changes in their pharmacokinetics. Corticosteroids also show decreased clearance as the patient ages. In severe cases of hypoalbuminemia, dose adjustment of mycophenolate acid derivatives may be necessary. However, the pharmacokinetic profiles of the mammalian target of rapamycin inhibitors, basiliximab, and rabbit anti-thymocyte globulin remain unaffected by age. Furthermore, age-related frailty may impact drug metabolism and require tailored interventions and closer follow-up. Although there is limited research, elderly liver transplant recipients require less immunosuppression with double or triple-agent regimens, lower exposure to calcineurin inhibitors, and a shorter course of corticosteroids. The usage of mammalian target of rapamycin inhibitors in older transplant populations has not been specifically investigated, and thus their usage should align with indications for younger patient groups.
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页数:8
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共 107 条
[1]   2018 Annual Report of the European Liver Transplant Registry (ELTR)-50-year evolution of liver transplantation [J].
Adam, Rene ;
Karam, Vincent ;
Cailliez, Valerie ;
Grady, John G. O. ;
Mirza, Darius ;
Cherqui, Daniel ;
Klempnauer, Jurgen ;
Salizzoni, Mauro ;
Pratschke, Johann ;
Jamieson, Neville ;
Hidalgo, Ernest ;
Paul, Andreas ;
Lopez Andujar, Rafael ;
Lerut, Jan ;
Fisher, Lutz ;
Boudjema, Karim ;
Fondevila, Constantino ;
Soubrane, Olivier ;
Bachellier, Philippe ;
Pinna, Antonio D. ;
Berlakovich, Gabriela ;
Bennet, William ;
Pinzani, Massimo ;
Schemmer, Peter ;
Zieniewicz, Krzysztof ;
Jimenez Romero, Carlos ;
De Simone, Paolo ;
Ericzon, Bo-Goran ;
Schneeberger, Stefan ;
Wigmore, Stephen J. ;
Fabregat Prous, Joan ;
Colledan, Michele ;
Porte, Robert J. ;
Yilmaz, Sezai ;
Azoulay, Daniel ;
Pirenne, Jacques ;
Line, Pal-Dag ;
Trunecka, Pavel ;
Navarro, Francis ;
Valdivieso Lopez, Andres ;
De Carlis, Luciano ;
Rufian Pena, Sebastian ;
Kochs, Eberhard ;
Duvoux, Christophe .
TRANSPLANT INTERNATIONAL, 2018, 31 (12) :1293-1317
[2]  
Aduen JF, 2009, MAYO CLIN PROC, V84, P973, DOI 10.1016/S0025-6196(11)60667-8
[3]   Evaluation of Early Allograft Function Using the Liver Graft Assessment Following Transplantation Risk Score Model [J].
Agopian, Vatche G. ;
Harlander-Locke, Michael P. ;
Markovic, Daniela ;
Dumronggittigule, Wethit ;
Xia, Victor ;
Kaldas, Fady M. ;
Zarrinpar, Ali ;
Yersiz, Hasan ;
Farmer, Douglas G. ;
Hiatt, Jonathan R. ;
Busuttil, Ronald W. .
JAMA SURGERY, 2018, 153 (05) :436-444
[4]   Evaluation of rejection, infection, and malignancy outcomes in elderly liver transplant recipients receiving a similar level of immunosuppression compared to a younger group [J].
Almalki, Bassem ;
Kane, Clare ;
Cunningham, Kathleen ;
D'Agostino, Carly ;
Novak, Antonia ;
Kapugi, Michelle ;
Ladner, Daniela ;
Schulte, Jamie .
TRANSPLANT IMMUNOLOGY, 2021, 69
[5]   Telomeres and age-related disease: how telomere biology informs clinical paradigms [J].
Armanios, Mary .
JOURNAL OF CLINICAL INVESTIGATION, 2013, 123 (03) :996-1002
[6]   Liver transplantation in the most severely ill cirrhotic patients: A multicenter study in acute-on-chronic liver failure grade 3 [J].
Artru, Florent ;
Louvet, Alexandre ;
Ruiz, Isaac ;
Levesque, Eric ;
Labreuche, Julien ;
Ursic-Bedoya, Jose ;
Lassailly, Guillaume ;
Dharancy, Sebastien ;
Boleslawski, Emmanuel ;
Lebuffe, Gilles ;
Kipnis, Eric ;
Ichai, Philippe ;
Coilly, Audrey ;
De Martin, Eleonora ;
Antonini, Teresa Maria ;
Vibert, Eric ;
Jaber, Samir ;
Herrerro, Astrid ;
Samuel, Didier ;
Duhamel, Alain ;
Pageaux, Georges-Philippe ;
Mathurin, Philippe ;
Saliba, Faouzi .
JOURNAL OF HEPATOLOGY, 2017, 67 (04) :708-715
[7]   Development and Validation of a Comprehensive Model to Estimate Early Allograft Failure Among Patients Requiring Early Liver Retransplant [J].
Avolio, Alfonso W. ;
Franco, Antonio ;
Schlegel, Andrea ;
Lai, Quirino ;
Meli, Sonia ;
Burra, Patrizia ;
Patrono, Damiano ;
Ravaioli, Matteo ;
Bassi, Domenico ;
Ferla, Fabio ;
Pagano, Duilio ;
Violi, Paola ;
Camagni, Stefania ;
Dondossola, Daniele ;
Montalti, Roberto ;
Alrawashdeh, Wasfi ;
Vitale, Alessandro ;
Teofili, Luciana ;
Spoletini, Gabriele ;
Magistri, Paolo ;
Bongini, Marco ;
Rossi, Massimo ;
Mazzaferro, Vincenzo ;
Di Benedetto, Fabrizio ;
Hammond, John ;
Vivarelli, Marco ;
Agnes, Salvatore ;
Colledan, Michele ;
Carraro, Amedeo ;
Cescon, Matteo ;
De Carlis, Luciano ;
Caccamo, Lucio ;
Gruttadauria, Salvatore ;
Muiesan, Paolo ;
Cillo, Umberto ;
Romagnoli, Renato ;
De Simone, Paolo .
JAMA SURGERY, 2020, 155 (12)
[8]   Clinical Pharmacokinetics and Pharmacodynamics of Prednisolone and Prednisone in Solid Organ Transplantation [J].
Bergmann, Troels K. ;
Barraclough, Katherine A. ;
Lee, Katie J. ;
Staatz, Christine E. .
CLINICAL PHARMACOKINETICS, 2012, 51 (11) :711-741
[9]   Our experience in liver transplantation in patients over 65 yr of age [J].
Bilbao, Itxarone ;
Dopazo, Cristina ;
Lazaro, Jose Luis ;
Castells, Luis ;
Escartin, Alfredo ;
Lopez, Inigo ;
Sapisochin, Gonzalo ;
Balsells, Joaquin ;
Margarit, Carlos .
CLINICAL TRANSPLANTATION, 2008, 22 (01) :82-88
[10]   Mammalian ABC transporters in health and disease [J].
Borst, P ;
Elferink, RO .
ANNUAL REVIEW OF BIOCHEMISTRY, 2002, 71 :537-592