Cumulative exposure to tacrolimus and incidence of cancer after liver transplantation.

Fecha de publicación: 01/03/2022 Fecha Ahead of Print: 14/03/2022

Autores de IIS La Fe

Tommaso Di Maira

Autor

Participantes ajenos a IIS La Fe

Rodríguez-Perálvarez M
Colmenero J
González A
Gastaca M
Curell A
Caballero-Marcos A
Sánchez-Martínez A
Herrero JI
Almohalla C
Lorente S
Cuadrado-Lavín A
Pascual S
López-Garrido MÁ
González-Grande R
Gómez-Orellana A
Alejandre R
Zamora J
Bernal-Bellido C
Chronic immunosuppression, cancer Spanish consortium

Grupos

Hepatología, Cirugia Hepatobiliopancreática y Trasplantes

Leader

Marina Berenguer Haym

Abstract

Cancer is the leading cause of death after liver transplantation (LT). This multicenter case-control nested study aimed to evaluate the effect of maintenance immunosuppression on post-LT malignancy. The eligible cohort included 2,495 LT patients who received tacrolimus-based immunosuppression. After 13,922 person/years follow-up, 425 patients (19.7%) developed malignancy (cases) and were matched with 425 controls by propensity score based on age, gender, smoking habit, etiology of liver disease and hepatocellular carcinoma (HCC) before LT. The independent predictors of post-LT malignancy were older age (HR=1.06 [95%CI 1.05-1.07]; p<0.001), male sex (HR=1.50 [95%CI 1.14-1.99]), smoking habit (HR=1.96 [95%CI 1.42-2.66]) and alcoholic liver disease (HR=1.53 [95%CI 1.19-1.97]). In selected cases and controls (n=850), the immunosuppression protocol was similar (p=0.51). An increased cumulative exposure to tacrolimus (CET), calculated by the area under curve of trough concentrations, was the only immunosuppression-related predictor of post-LT malignancy after controlling for clinical features and baseline HCC (CET at 3 months p=0.001 and CET at 12 months p=0.004). This effect was consistent for de novo malignancy (after excluding HCC recurrence) and for internal neoplasms (after excluding non-melanoma skin cancer). Therefore, tacrolimus minimization, as monitored by CET, is the key to modulate immunosuppression in order to prevent cancer after LT.

Datos de la publicación

ISSN/ISSNe:: 1600-6135, 1600-6143
Tipo:: Article
Páginas:: 1671-1682
DOI:: 10.1111/ajt.17021
Factor de Impacto:: 3,311 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Métricas

Filiaciones

Rodríguez-Perálvarez M:: Department of Hepatology and Liver Transplantation, Hospital Universitario Reina Sofía, IMIBIC and University of Córdoba, Córdoba, Spain

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
Colmenero J:: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain

Liver Transplantation Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain
González A:: Department of Hepatology, Hospital Universitario Ntra. Sra. de la Candelaria, Tenerife, Spain
Gastaca M:: Hepatobiliary Surgery and Liver transplantation Unit, Hospital Universitario Cruces, University of the Basque Country and Biocruces Bizkaia Health Research Institute, Bilbao, Spain
Curell A:: Department of HPB Surgery and Transplantation, Hospital Universitario Vall d´Hebron, Barcelona, Spain
Caballero-Marcos A:: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain

Department of Hepatology and Liver Transplantation, Hospital General Universitario Gregorio Marañón, Madrid, Spain
Sánchez-Martínez A:: Liver Transplantation Unit. Hospital Universitario Virgen de la Arrixaca and IMIB, Murcia, Spain
Di Maira T:: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain

Liver Transplantation and Hepatology Unit, Hospital Universitari i Politècnic La Fe, Valencia, Spain
Herrero JI:: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain

Liver Unit, Clínica Universidad de Navarra and IdiSNA, Pamplona, Spain
Almohalla C:: Department of Hepatology and Liver Transplantation, Hospital Universitario Río Hortega, Valladolid, Spain
Lorente S:: Department of Hepatology and Liver Transplantation, Hospital Clínico Lozano Blesa, University of Zaragoza and ISS Aragón, Zaragoza, Spain
Cuadrado-Lavín A:: Department of Gastroenterology and Hepatology, Marqués de Valdecilla University Hospital, University of Cantabria and IDIVAL, Santander, Spain
Pascual S:: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain

Department of Hepatology and Liver Transplantation, Hospital General Universitario Alicante and ISABIAL, Alicante, Spain
López-Garrido MÁ:: Department of Hepatology and Liver Transplantation, Hospital Universitario Virgen de las Nieves, Granada, Spain
González-Grande R:: Department of Hepatology and Liver Transplantation, Hospital Regional Universitario de Málaga, Málaga, Spain
Gómez-Orellana A:: Department of Computer Science and Numerical Analysis, University of Córdoba, Córdoba, Spain
Alejandre R:: Department of Hepatology and Liver Transplantation, Hospital Universitario Reina Sofía, IMIBIC and University of Córdoba, Córdoba, Spain
Zamora J:: Department of Hepatology and Liver Transplantation, Hospital Universitario Reina Sofía, IMIBIC and University of Córdoba, Córdoba, Spain
Bernal-Bellido C:: Hepato-Biliary-Pancreatic Surgery Unit and Transplantation. Hospital Universitario Virgen del Rocío, Sevilla, Spain