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

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.