Heme Oxygenase-1 as a Predictor of Early Allograft Dysfunction in Liver Transplantation: A Prospective Observational Pilot Study

Abstract

<jats:sec> <jats:title>Background.</jats:title> <jats:p>Early allograft dysfunction (EAD), defined as hepatic insufficiency within a week of orthotopic liver transplantation (OLT), affects up to 25% of recipients and is associated with morbidity and mortality. Ischemia–reperfusion injury (IRI), the primary driver of EAD, reflects immune and cellular dysregulation triggered by transient tissue oxygen deprivation. Heme oxygenase-1 (HO-1), a cytoprotective enzyme, plays a central role in mitigating hepatic IRI. We hypothesized a distinct perioperative HO-1 signature correlates with EAD.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods.</jats:title> <jats:p>We conducted a prospective observational pilot study of 43 primary adult, deceased donor OLT recipients at Emory University Hospital between August 2023 and July 2024. EAD was defined by the Olthoff criteria, using serum bilirubin, international normalized ratio (INR), and aminotransferases. Perioperative arterial serum was assayed preimplantation at anesthesia induction (timepoint, T1), and 2 (T2), and 48 h (T3) postimplantation to measure HO-1 using multiplex immunoassay and compared between recipients with and without EAD. Group comparisons (EAD versus non-EAD) used Mann-Whitney U for continuous variables (reported as medians) and chi-square or Fisher exact test for categorical variables. HO-1 changes over time were assessed with the Friedman test and post hoc comparisons. The Spearman correlation evaluated associations between HO-1 and clinical parameters.</jats:p> </jats:sec> <jats:sec> <jats:title>Results.</jats:title> <jats:p> EAD occurred in 9 of 43 patients (20.9%). Recipients who developed EAD exhibited significantly higher HO-1 levels 2 h postimplantation (T2) (22,665 pg/mL [interquartile range (IQR): 17 881, 25 361] versus 10,765 pg/mL [IQR: 8060, 18 903], <jats:italic toggle="yes">P</jats:italic> = 0.0284) and a significantly greater peri-implantation rise in HO-1 levels (T2-T1) (21,050 pg/mL[IQR: 17 645, 24 765] versus 9,264 pg/mL [IQR: 6876,17514], <jats:italic toggle="yes">P</jats:italic> = 0.0358), compared with those without EAD. Receiver operating characteristic curve analysis revealed moderate predictive ability of the peri-implantation rise in HO-1 levels (T2-T1) (area under the curve = 0.7157). </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions.</jats:title> <jats:p>Peri-implantation HO-1 kinetics may represent a novel biomarker of EAD. Larger validation studies and mechanistic investigations are warranted to refine risk stratification and guide targeted interventions to mitigate EAD.</jats:p> </jats:sec>