Núñez K, Hamed M, Fort D, Bruce D, Thevenot P, Cohen A. Links between donor macrosteatosis, interleukin-33 and complement after liver transplantation. World J Transplant 2020; 10(5): 117-128 [PMID: 32864357 DOI: 10.5500/wjt.v10.i5.117]
Corresponding Author of This Article
Ari Cohen, MD, Professor, Surgeon, Multi-Organ Transplant, Ochsner Clinic Foundation, 1514 Jefferson Hwy, New Orleans, LA 70121, United States. acohen@ochsner.org
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Retrospective Cohort Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Transplant. May 29, 2020; 10(5): 117-128 Published online May 29, 2020. doi: 10.5500/wjt.v10.i5.117
Links between donor macrosteatosis, interleukin-33 and complement after liver transplantation
Kelley Núñez, Mohammad Hamed, Daniel Fort, David Bruce, Paul Thevenot, Ari Cohen
Kelley Núñez, Mohammad Hamed, Paul Thevenot, Institute of Translational Research, Ochsner Clinic Foundation, New Orleans, LA 70121, United States
Daniel Fort, Center for Outcomes and Health Services Research, Research Administration, Ochsner Clinic Foundation, New Orleans, LA 70121, United States
David Bruce, Ari Cohen, Multi-Organ Transplant Program, Ochsner Clinic Foundation, New Orleans, LA 70121, United States
Author contributions: Thevenot P and Cohen A designed the research; Núñez K and Hamed M performed the research; Núñez K, Fort D, Bruce D, and Thevenot P analyzed the data; Núñez K wrote the manuscript; Hamed M, Thevenot P, and Cohen A revised the manuscript.
Institutional review board statement: This study was reviewed and approved by the Ochsner Institutional Review Board.
Informed consent statement: All patients in this study provided informed consent.
Conflict-of-interest statement: Authors have no conflict of interests to disclose.
Data sharing statement: No additional data are available for this study.
STROBE statement: Authors have read the STROBE Statement checklist of items and the manuscript was prepared and revised according to the STROBE Statement checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Ari Cohen, MD, Professor, Surgeon, Multi-Organ Transplant, Ochsner Clinic Foundation, 1514 Jefferson Hwy, New Orleans, LA 70121, United States. acohen@ochsner.org
Received: December 31, 2019 Peer-review started: December 31, 2019 First decision: March 26, 2020 Revised: April 7, 2020 Accepted: May 5, 2020 Article in press: May 5, 2020 Published online: May 29, 2020 Processing time: 149 Days and 11 Hours
ARTICLE HIGHLIGHTS
Research background
Due to the rise in nonalcoholic fatty liver disease, grafts with macrosteatosis will become more frequent in the donor pool. The use of macrosteatotic donor grafts for transplantation are associated with increased risk of graft failure and patient mortality. Factors that predict which macrosteatotic grafts are safe for transplantation remain limited.
Research motivation
The motivation for this study was to identify biomarkers immediately following reperfusion during transplantation with macrosteatotic grafts that predict increased injury post-transplant.
Research objectives
The objective of this study was to investigate the relationship between interleukin-33 and activated complement (C3a and C5a) with liver dysfunction in recipients immediately following liver reperfusion transplanted with either < 30% or ≥ 30% macrosteatotic grafts.
Research methods
The cohort consisted of recipients transplanted with either < 30% or ≥ 30% macrosteatotic grafts. Blood was collected immediately following reperfusion with quantification of interleukin-33 and activated complement (C3a and C5a) levels. Punch biopsies in a subset of donor grafts (n = 22) were used for microRNA expression analysis.
Research results
Recipients transplanted with ≥ 30% macrosteatotic grafts had significantly higher ALT and AST levels, increased risk of early allograft dysfunction, and higher levels of interleukin-33 and activated complement (C3a and C5a) post-transplant compared to recipients transplanted with < 30% macrosteatotic grafts. Additionally, upregulation of pro-inflammatory genes were found in macrosteatotic grafts.
Research conclusions
Quantification of interleukin-33 and activated complement (C3a and C5a) immediately following reperfusion during transplantation can provide insight into which recipients are at increased risk of early allograft dysfunction.
Research perspectives
This study provides additional justification for targeting activated complement in macrosteatotic grafts prior to transplantation.
