Recruitment of inflammatory monocytes after liver transplantation and correlation with clinical outcome

Robertson, Francis; Male, Victoria; Wright, Graham; Fuller, Barry; Davidson, Brian

Abstract

Background
Ischaemia reperfusion injury is a key cause of mortality and graft loss after liver transplantation. After tissue injury, monocytes are rapidly mobilised and recruited to injured tissue by monocyte chemoattractant protein-1 (MCP-1). Elevated MCP-1 concentrations correlate with poorer outcomes in patients after haemorrhagic stroke but have not been evaluated as a prognostic marker in clinical liver transplantation. We aimed to assess the role of inflammatory monocytes and MCP-1 in ischaemia reperfusion injury
Methods
Adult patients undergoing liver transplantation at the Royal Free Hospital, London, UK, were recruited. Liver biopsy samples were collected preimplantation and 2 h after reperfusion from five patients. Intrahepatic mononuclear cells were extracted for immediate analysis by flow cytometery. Plasma MCP-1 concentrations from 33 patients were measured preoperatively by ELISA, 2 h and 24 h after reperfusion, and correlated with graft function by measurement of day 3 aspartate aminotransferase (AST) and early allograft dysfunction (EAD) score.
Findings
Flow cytometric analysis demonstrated an increase in mean classical monocytes after reperfusion compared with preimplantation (4·18% of total live cells [SD 2·61] vs 0·61 [0·38], p=0·018). In three of the five recipients we distinguished cells of donor versus recipient origin by HLA-A allele expression to demonstrate that 88% (6·24) of the classical monocytes were recipient derived in the postreperfusion biopsy sample. Median MCP-1 concentrations were significantly raised after reperfusion (385·61 pg/mL [IQR 244·75–715·20] vs 71·2 [55·61–113·99], pvs 47·44 [29·53–77·73], p=0·037). MCP-1 concentrations at 24 h correlated with day 3 AST concentrations (p=0·002).
Interpretation
Our results show that classical monocytes are rapidly recruited to the liver after ischaemia reperfusion injury, and that high MCP-1 concentrations at 24 h are associated with poorer graft function. Therefore, MCP-1 blockade presents an attractive strategy to reduce graft ischaemia reperfusion injury.

• Presentation Conference Type: Poster
• Start Date: Feb 23, 2017
• Publication Date: 2017-02
• Deposit Date: Aug 21, 2019
• Journal: The Lancet
• Print ISSN: 0140-6736
• Publisher: Elsevier
• Volume: 389
• Pages: S84
• Series Title: Spring Meeting for Clinician Scientists in Training 2017
• Series ISSN: 01406736
• DOI: https://doi.org/10.1016/s0140-6736%2817%2930480-4
• Public URL: http://researchrepository.napier.ac.uk/Output/1432648
• Publisher URL: http://linkinghub.elsevier.com/retrieve/pii/S0140673617304804