Postreperfusion Liver Biopsy as Predictor of Early Graft Dysfunction and Survival After Orthotopic Liver Transplantation

Abstract

Background: Postreperfusion liver biopsy (PRB) can assess the degree of ischemia/reperfusion injury (IRI) after orthotopic liver transplantation (OLT). The influence of IRI on graft outcomes and overall survival is controversial.

Aim: To determine the correlation between the severity of IRI in PRB and overall graft and patient survival and, secondarily, to identify factors on PRB that predict poor graft outcomes.

Methods: This is a retrospective analysis of all patients who underwent OLT using donation after brain death (DBD) with PRB. The severity of IRI in PRB was graded. Predictors of IRI were assessed using univariate and multivariate analysis and the Kaplan-Meier with log rank test for the graft and overall survival, respectively.

Results: We included 280 OLTs (64.7%). The histopathological assessment of IRI severity was as follows: no IRI (N = 96, 34.3%), mild IRI (N = 65; 23.2%), moderate IRI (N = 101; 36.1%), and severe IRI (N = 18; 6.4%). The incidence rates of initial good graft function (IGGF), primary nonfunction and early allograft dysfunction (EAD) were 32.5%, 3.9%, and 18.6%, respectively. Severe IRI was associated with a lower incidence of IGGF (OR: 0.34, 95% CI 0.12-0.92; P = 0.03). Patients with severe IRI tended to have a higher incidence of EAD (33.2% vs. 18.6, P = 0.23). The cold ischemia time was an independent predictor of severe IRI on the multivariate analysis. Severe IRI was associated with poor 1- and 5-year overall survival rates (67% and 44%, respectively, compared with 84 and 68% in nonsevere IRI). Patients with severe IRI exhibited worse graft and overall survival.

Conclusions: Cold ischemia time predicts the development of severe IRI. Patients with severe IRI show worse graft and overall survival and a lower incidence of IGGF, suggesting that histopathological findings could be useful for identifying patients at high risk of worse outcomes after OLT.

Keywords: ALD, alcohol-related liver disease; ALF, acute liver failure; ALT, alanine aminotransferase; CIHD, chronic ischaemic heart disease; CNI, calcineurin inhibitors; COPD, chronic obstructive pulmonary disease; DBD, donation after brain death; EAD, early allograft dysfunction; H&E, hematoxylin and eosin; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; IGGF, initial good graft function; IQR, interquartile range; IRI, ischaemia/reperfusion injury; MELD, Model for End-stage Liver Disease; OLT, orthotopic liver transplantation; ONT, Organización Nacional de Transplantes; PBC, primary biliary cholangitis; PNF, primary nonfunction; PRB, postreperfusion liver biopsy; SD, standard deviation; STROBE, Strengthening the Reporting of Observational studies in Epidemiology; cold ischemia time; early allograft dysfunction; ischemia reperfusion injury; liver transplantation; postreperfusion biopsy.

Figure 1

The histologic range of ischaemia reperfusion injury (IRI). (A) H&E staining (40×) of mild IRI demonstrating no large clusters of intrasinusoidal neutrophils among centrilobular hepatocytes. (B) H&E staining (40×) of moderate IRI demonstrating centrilobular necrosis of several clusters of neutrophils (asterisk) with hepatocyte damage (arrow). (C) H&E staining (10×) of severe IRI showing centrilobular coagulative necrosis and confluent cell loss (arrows).

Figure 2

Severity of ischaemia reperfusion injury according to the histopathological assessment of postreperfusion biopsy. IRI, ischaemia reperfusion injury.

Figure 3

(A) Kaplan–Meier analysis of overall survival according to the grade of ischaemia/reperfusion injury. A significantly worse overall survival was observed in patients with severe ischaemia/reperfusion injury than in those with nonsevere injury (Log Rank P = 0.04). (B) Kaplan–Meier analysis of graft survival according to the grade of ischaemia/reperfusion injury. Notice that there is a significant worse outcome in patients with severe IRI (Log Rank P = 0.025).