The Pro-Inflammatory Profile of Alcoholic Patients Increases Risk for Ischemia-Reperfusion Injury During Orthotopic Liver Transplantation
1Department of Pathology and Laboratory Medicine, UCLA, Los Angeles, CA, 2Department of Surgery, UCLA, Los Angeles, CA, 3Departments of Pathology and Laboratory Medicine and Surgery, UCLA, Los Angeles, CA
Meeting: 2020 American Transplant Congress
Abstract number: D-205
Keywords: Alcohol, Inflammation, Ischemia, Liver transplantation
Session Information
Session Name: Poster Session D: Non-Organ Specific: Organ Preservation/Ischemia Reperfusion Injury
Session Type: Poster Session
Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
Location: Virtual
*Purpose: Ischemia-reperfusion injury (IRI) elicits cellular damage which triggers a pro-inflammatory immune response that can lower allograft survival in orthotopic liver transplant (OLT) patients. In our OLT patient cohort, 56/113 (50%) had biopsy-proven IRI (IRI+), but patients with alcoholism (EtOH+) as an etiology necessitating OLT were disproportionally affected (21/33; 64% IRI+). The innate immune response can either promote or help resolve IRI depending on its activation to a pro- or anti-inflammatory state. Therefore, we tested EtOH- and EtOH+ OLT patient blood for differences in cytokines and the effect of these cytokines on myeloid cell differentiation.
*Methods: OLT patient peripheral blood was collected pre-OLT (PO). Two intraoperative blood samples were also collected: portal vein blood before liver reperfusion (PV) and immediately following liver reperfusion (LF). 38-plex Luminex cytokine analysis was performed on all blood samples. IHC for neutrophil and myeloid cell infiltration was performed on intraoperative pre- and post-reperfusion biopsies of donor organs. Healthy third-party monocytes were exposed to LF blood for 3 days; a panel of immunomodulatory surface markers was analyzed by flow cytometry.
*Results: EtOH+ patient blood had higher levels of cytokines compared to EtOH- patient blood at all timepoints: PO (Flt3L, p<0.05), PV (IL3, IL1Ra, p<0.05; IL8, MIP1β, p<0.01); and LF (IL3, p<0.05). Paired analysis showed larger decreases between corresponding PV and LF samples in EtOH+ patients for CXCL1 (p<0.05) and IL8 (p<0.01) compared to EtOH- patients. Neutrophil infiltration trended towards a significant increase from pre- to post-reperfusion biopsies in EtOH+ patients (p=0.056). Myeloid infiltration also increased pre-to post-reperfusion in EtOH+ patients (p<0.05). No such trends were seen in EtOH- patient biopsies. EtOH+ patient LF increased Gal-9 expression (p<0.05) and EtOH- patient LF induced TIM-4 (p<0.05) and PD-L1 (p=0.061) expression on monocyte-derived macrophages.
*Conclusions: EtOH+ OLT recipients showed higher Flt3L, IL3, MIP1β, IL8, and CXCL1 levels that can increase dendritic cell development (Flt3L) and neutrophil chemotaxis (others). Exposure to EtOH+ LF polarized monocytes to a more pro-inflammatory phenotype with increased Gal-9 expression, and a concurrent decrease of TIM-4 and PD-L1. Together, the pro-inflammatory immune profile seen before, during, and after allograft reperfusion can be a contributing factor to the disproportionate occurrence of IRI in EtOH+ OLT patients.
To cite this abstract in AMA style:
Terry AQ, Sosa RA, Rossetti M, Li F, Nevarez-Mejia J, Naini BV, Kaldas FM, Groysberg VM, Younan SM, Busuttil RW, Gjertson DW, Kupiec-Weglinski JW, Reed EF. The Pro-Inflammatory Profile of Alcoholic Patients Increases Risk for Ischemia-Reperfusion Injury During Orthotopic Liver Transplantation [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/the-pro-inflammatory-profile-of-alcoholic-patients-increases-risk-for-ischemia-reperfusion-injury-during-orthotopic-liver-transplantation/. Accessed May 16, 2025.« Back to 2020 American Transplant Congress