Predictive biomarkers of early allograft dysfunction after liver transplantation: A prospective pilot study.

Abstract

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, χ ² 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.