Because of the shortage of liver grafts available for transplantation, the restrictions on graft quality have been relaxed, and marginal grafts, such as steatotic livers, are now accepted. However, this policy change has not solved the problem, because steatotic liver grafts tolerate ischemia-reperfusion (I/R) injury poorly. Adipocytokines differentially modulate steatosis, inflammation, and fibrosis and are broadly present in hepatic resections and transplants. The potential use of adipocytokines as biomarkers of the severity of steatosis and liver damage to aid the identification of high-risk steatotic liver donors and to evaluate hepatic injury in the postoperative period are discussed. The hope of finding new therapeutic strategies aimed specifically at protecting steatotic livers undergoing surgery is a strong impetus for identifying the mechanisms responsible for hepatic failure after major surgical intervention. Hence, the most recently described roles of adipocytokines in steatotic livers subject to I/R injury are discussed, the conflicting results in the literature are summarized, and reasons are offered as to why strategic pharmacologic control of adipocytokines has yet to yield clinical benefits. After this, the next steps needed to transfer basic knowledge about adipocytokines into clinical practice to protect marginal livers subject to I/R injury are presented. Recent strategies based on adipocytokine regulation, which have shown efficacy in various pathologies, and hold promise for hepatic resection and transplantation are also outlined.
1 Transplant Biomedicals, S.L, Barcelona, Spain.
2 Hospital Regional de Alta Especialidad de Ciudad Victoria “Bicentenario 2010”, Ciudad Victoria, México.
3 Facultad de Medicina e Ingeniería en Sistemas Computacionales de Matamoros, Universidad Autónoma de Tamaulipas, México.
4 Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
5 Liver Vascular Biology Research Group, Institut d´Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
6 Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.
7 Facultad de Medicina, Universidad International de Cataluña, Barcelona, Spain.
Received 23 June 2017. Revision received 5 December 2017.
Accepted 7 December 2017.
M.B.J.-C. and A.C.-R. contributed equally to this work.
This research was supported by the Ministerio de Economía y Competitividad (MINECO) (project grant SAF2015-64857-R) Madrid, Spain; by the European Union (Fondos FEDER, “una manera de hacer Europa”); by CERCA Program/Generalitat de Catalunya and by the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement (project grant 2014_SGR_144) Barcelona, Spain; and by the Consejo Nacional de Ciencia y Tecnología (CONACYT), Convocatoria de Proyectos de Desarrollo Científico para Atender Problemas Nacionales (Project grant 248368), México. Jiménez-Castro M.B. has a contract from the Programa de Promoción del talento y su empleabilidad—Ministerio de Economía y Competitividad (grant EMP-TU-2015-4167) Madrid, Spain; and Avalos de Leon C.G. is the recipient of a fellowship from CONACYT (grant 411424), México.
The authors of this article declare no conflicts of interest.
E.N.-S. and C.A.-L. participated in the data acquisition. M.J.-C., A.C.-R., and J.G.-S. collected and analyzed the data. M.J.-C., A.C.-R., J.G.-S., and C.P. contributed to the preparation and writing of this review. C.P. provided critical appraisal of the article, expertise, review, and editorial assistance.
Correspondence: Carmen Peralta, PhD, Institut d´Investigacions Biomèdiques August Pi i Sunyer, Esther Koplowitz Center, Roselló 149-153, 3rd floor, Office 3.8, 08036 Barcelona, Spain. (firstname.lastname@example.org).