Effects of donor macrosteatosis and post transplant and post transplant complement activation on early allograft dysfunction in liver transplant patients

Abstract

Presenter: Kelley Nunez PhD | Ochsner Health System Background: Liver transplantation provides a curative option for patients with underlying cirrhosis. However, organ shortage continues to increase waitlist mortality. To combat this, less than optimal organs have been used for transplantation. These extended criteria donor grafts are accompanied by increased risk of both graft failure and decreased patient survival. In this study, we investigated the impact of donor Macrosteatosis on early allograft dysfunction, complement activation, and inflammatory mediators in recipients. Methods: Cohort consisted of patients who received a liver transplant at Ochsner Medical Center from November 2011 – April 2019. Clinical variables and donor macrosteatosis percentages were retrospectively extracted from the electronic medical record. Recipient blood samples were collected immediately following liver transplantation in a subset of cohort. Multiple indices to determine early allograft dysfunction were calculated, and ELISA’s were performed on the blood samples for complement activation measurements and damage associated molecular proteins. Results: Cohort consisted of 1322 patients with median Donor age of 44, 58% male. Increases in donor Macrosteatosis led to significant increases in liver enzymes, INR, and bilirubin, all measures of liver damage. Higher levels of early allograft dysfunction were also found in patients receiving donor grafts with > 20% macrosteatosis. These patients had increased complement activation of both C3a and C5a, and significantly higher levels of the alarmin IL-33. Conclusion: Recipients that receive donor grafts with > 20% macrosteatosis have higher levels of liver damage, complement activation, and alarmin release. Proactive measures of lower complement activation may decrease presence of early allograft dysfunction.