Beyond graft function impairment after liver transplantation: the prolonged cold ischemia time impact on recurrence of hepatocellular carcinoma after liver transplantation-a single-center retrospective study.

ABSTRACT

Purpose: Hepatocellular carcinoma (HCC) is one of the malignant tumors responsible for high mortality and recurrence rates. Although liver transplantation (LT) is an effective treatment option for HCC, ischemia-reperfusion injury (IRI) is a contributor to HCC recurrence after LT. Moreover, prolonged cold ischemia time (CIT) is a risk factor for IRI during LT, and there is insufficient clinical evidence regarding the impact of CIT on HCC recurrence after LT. Patients and Methods: This retrospective study analyzed 420 patients who underwent LT for HCC between February 2015 and November 2020 at The First Affiliated Hospital, Sun Yat-sen University. The duration of CIT was defined as the time from clamping of the donor aorta until portal reperfusion. Results: A total of 133 patients (31.7%) experienced tumor recurrence after LT, and CIT > 568 min was the independent risk factor for HCC recurrence (OR, 2.406; 95% CI [1.371-4.220]; p = 0.002). Multivariate Cox's regression analysis revealed that the recipients' gender, exceeding Milan criteria, poor differentiation, and alpha-fetoprotein (AFP) ≥400 ng/ml in CIT > 568 min group were independent risk factors for disease-free survival. The peak 7-day postoperative alanine aminotransferase (ALT) level (p < 0.001), the peak 7-day postoperative aspartate aminotransferase (AST) level (p < 0.001), the peak 7-day postoperative peak total bilirubin (TBIL) level (p = 0.012), and the incidence of early allograft dysfunction (EAD) (p = 0.006) were significantly higher in the CIT > 568 min group compared to the CIT ≤ 568 min group. Moreover, the amount of fresh frozen plasma (FFP) infusion during the operation increased (p = 0.02), and the time of mechanical ventilation postoperative was longer (p = 0.045). Conclusion: An effective strategy to improve the prognosis is to reduce CIT; this strategy lowers the recurrence of HCC in patients undergoing LT, especially those within the Milan criteria.