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World J Transplant. Sep 18, 2026; 16(3): 121567
Published online Sep 18, 2026. doi: 10.5500/wjt.121567
Predictive biomarkers of early allograft dysfunction after liver transplantation: A prospective pilot study
Elizabeth A Wilson, Ammar Rashied, Jamie R Privratsky, Mara Serbanescu, Andrew S Barbas, Kirsten M Williams, Craig M Coopersmith
Elizabeth A Wilson, Jamie R Privratsky, Mara Serbanescu, Department of Anesthesiology, Duke University School of Medicine, Durham, NC 27707, United States
Ammar Rashied, Department of Biostatistics and Bioinformatics, Emory University Rollins School of Public Health, Atlanta, GA 30322, United States
Andrew S Barbas, Department of Surgery, Division of Abdominal Transplant Surgery, Duke University School of Medicine, Durham, NC 27710, United States
Kirsten M Williams, Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Emory University School of Medicine, Atlanta, GA 30322, United States
Craig M Coopersmith, Department of Surgery, Emory Critical Care Center, Emory University School of Medicine, Atlanta, GA 30322, United States
Author contributions: Wilson EA initiated the study; Wilson EA, Williams KM, and Coopersmith CM participated in the research design and conception of the work; Patient recruitment and enrollment was performed by Wilson EA and the OXIDATIVE study group; Sample acquisition and processing and data acquisition/management was performed by Wilson EA; Wilson EA, Privratsky JR, Serbanescu M, Barbas AS, Williams KM, and Coopersmith CM were involved in interpretation of the results; Rashied A performed the statistical analyses; and all authors were involved in data discussion, revised the work for its intellectual content, and reviewed and approved the final version of the manuscript.
Supported by the Robert W Woodruff Health Science Center and the National Center for Advancing Translational Sciences of the National Institutes of Health under Award, No. UL1TR002378; the International Liver Transplantation Society Vanguard Research Award; and the National Institutes of Health held by CMC, No. 5R35GM148217-04.
Institutional review board statement: This study was reviewed and approved by the Emory University Institutional Review Board (IRB) under protocol number 5728.
Informed consent statement: Written, informed consent was obtained by all study participants, or their legal guardian, confidentially in accordance with the Declaration of Helsinki and Istanbul and participation did not affect medical care.
Conflict-of-interest statement: All authors declare that they have no conflict of interest to disclose.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Corresponding author: Elizabeth A Wilson, MD, Assistant Professor, Principal Investigator, Department of Anesthesiology, Duke University School of Medicine, 2301 Erwin Road, Durham, NC 27707, United States.
elizabeth.a.wilson@duke.edu
Received: March 27, 2026
Revised: April 20, 2026
Accepted: May 8, 2026
Published online: September 18, 2026
Processing time: 155 Days and 19.4 Hours
BACKGROUND
Early allograft dysfunction (EAD) contributes to significant morbidity and mortality. Although EAD can occur after any preservation method, the risk is higher with static cold storage (SCS) - still the predominant modality worldwide - given its longer ischemia time. We hypothesize specific peri-implantation alterations in serum cytokine and transcription factor levels are associated with EAD in recipients of allografts preserved using SCS.
AIM
To identify peri-implantation predictive biomarkers of EAD in SCS recipients.
METHODS
We conducted a prospective single-center pilot study of adult deceased donor SCS-preserved liver transplant recipients from August 2023 to July 2024. EAD was defined by the Olthoff criteria. Arterial serum was obtained pre-implantation (timepoint, T1) and 2 (T2) and 48 hours (T3) post-implantation to measure biomarker levels by multiplex immunoassay. Biomarker levels between non-EAD and EAD groups, and their associations with clinical outcomes, were compared using Mann-Whitney U, χ2 or Fisher’s exact, Friedman, Wilcoxon Z, and Spearman correlation tests.
RESULTS
EAD occurred in 8 of 24 SCS recipients (33.3%). Compared with non-EAD recipients, those with EAD had lower interleukin-6 (IL-6) levels at T1 [6.3 pg/mL interquartile ranges (IQR): 3.7, 12.9 vs 15.4 pg/mL IQR: 8.7, 24.9, P = 0.0433], greater peri-implantation increases in induced protein 10 (IP-10) (T2-T1) [386.7 pg/mL (IQR: -26.7, 1280.7) vs -181.5 pg/mL (IQR: -452.4, 145.9), P = 0.02], and higher 48-hour post-implantation hypoxia inducible factor-1 alpha (HIF-1α) levels at T3 [611.2 pg/mL (IQR: 384.7, 869.9) vs 157.9 pg/mL (IQR: 110, 273), P = 0.0095]. Discriminatory performance was moderate-to-strong for pre-implantation IL-6 [area under the curve (AUC) = 0.7578], peri-implantation IP-10 (AUC = 0.7969), and 48-hour post-implantation HIF-1α (AUC = 0.8889).
CONCLUSION
When integrated with established risk factors and pending external validation, these biomarkers may predict EAD and enhance early risk stratification in SCS recipients.
Core Tip: Early allograft dysfunction (EAD) remains common in liver transplantation, affecting roughly 20%-25% of recipients of allografts preserved via static cold storage, the traditional mode of organ preservation. Dynamic changes in serum cytokine and transcription factor levels - lower baseline interleukin-6, rising interferon-gamma-induced protein 10 peri-implantation, and elevated post-implantation hypoxia inducible factor-1 alpha are associated with EAD, suggesting potential early biomarkers. After validation in a larger study, peri-implantation biomarker profiling may help identify high-risk allografts early, potentially guiding management.
