Ischemic-Free Liver Transplantation Reduces the Recurrence of Hepatocellular Carcinoma After Liver Transplantation

Abstract

Ischemia reperfusion injury (IRI) is an adverse factor for hepatocellular carcinoma (HCC) recurrence after liver transplantation. Ischemic-free liver transplantation (IFLT) is a novel transplant procedure that can largely reduce or even prevent IRI, but the clinical relevance of IFLT and the recurrence of HCC after liver transplantation are still unknown. This retrospective study compared survival outcomes, HCC recurrence, perioperative data and IRI severity following liver transplantation (LT). 30 patients received IFLT and 196 patients received conventional liver transplantation (CLT) were chosen for the entire cohort between June 2017 and August 2020. A 1:3 propensity score matching was performed, 30 IFLT recipients and 85 matched CLT patients were enrolled in propensity-matched cohorts. An univariate and multivariate Cox regression analysis was performed, and showed surgical procedure (CLT vs IFLT) was an independent prognostic factor (HR 3.728, 95% CI 1.172-11.861, P=0.026) for recurrence free survival (RFS) in HCC patients following liver transplantation. In the Kaplan–Meier analysis, the RFS rates at 1 and 3 years after LT in recipients with HCC in the IFLT group were significantly higher than those in the CLT group both in the entire cohort and propensity-matched cohort (P=0.006 and P=0.048, respectively). In addition, patients in the IFLT group had a lower serum lactate level, lower serum ALT level and serum AST level on postoperative Day 1. LT recipients with HCC in the IFLT group had a lower incidence of early allograft dysfunction than LT recipients with HCC in the CLT group. Histological analysis showed no obvious hepatocyte necrosis or apoptosis in IFLT group. In conclusion, IFLT can significantly reduce IRI damage and has the potential to be a useful strategy to reduce HCC recurrence after liver transplantation.

One Shoot, Two Birds: Alleviating Inflammation Caused by Ischemia/Reperfusion Injury to Reduce the Recurrence of Hepatocellular Carcinoma

“…Its application is able to procure, preserve, and implant liver grafts from DBD donors without stopping the blood and oxygen supply, thus entirely preventing hepatic IRI ( 26 ). A recent propensity-matched cohort study showed that IFLT recipients had a higher RFS rate at 1 and 3 years (92.2% and 86.7%) than conventional LT recipients (88.1% and 53.6%), with much lower liver damage ( 27 ). Though the oncological benefit of IFLT needs further observation and validation in a larger sample, this technique shows enormous potential not only for completely avoiding IRI but also for preventing associated HCC recurrence.…”

Mitochondria and Cancer Recurrence after Liver Transplantation—What Is the Benefit of Machine Perfusion?

“…Interestingly, one study demonstrated the protective effect of IFOT in recipients with HCC. Lower recurrence rates were seen through an IRI reduction [ 137 ]. In this propensity score matched analysis, the authors illustrated a better recurrence-free survival after IFOT (HR 3.728, 95% CI 1.172–11.861, p = 0.026), when compared to SCS alone [ 137 ].…”

“…Lower recurrence rates were seen through an IRI reduction [ 137 ]. In this propensity score matched analysis, the authors illustrated a better recurrence-free survival after IFOT (HR 3.728, 95% CI 1.172–11.861, p = 0.026), when compared to SCS alone [ 137 ]. The authors showed recurrence-free survival rates at 1 and 3 years after LT in recipients with HCC in the IFOT group of 92% and 87%, respectively, which were significantly higher than those (73.0% and 46.3%) seen in the cold storage group [ 137 ].…”

“…In this propensity score matched analysis, the authors illustrated a better recurrence-free survival after IFOT (HR 3.728, 95% CI 1.172–11.861, p = 0.026), when compared to SCS alone [ 137 ]. The authors showed recurrence-free survival rates at 1 and 3 years after LT in recipients with HCC in the IFOT group of 92% and 87%, respectively, which were significantly higher than those (73.0% and 46.3%) seen in the cold storage group [ 137 ]. Looking at the HCC burden, in the entire cohort, the pre-transplant AFP level was higher in the non-IFOT group compared to the IFOT group ( p = 0.016).…”

“…The percentage of LT recipients within the Milan criteria and micro-vascular invasion were also higher in the non-IFOT group than in the IFOT group ( p = 0.032 and p = 0.042, respectively). There were no differences in the size of the largest HCC lesion, the number of lesions, tumor differentiation, or the type of previous treatment between the two groups [ 137 ]. The two clinical studies with the impact of HOPE and IFOT are summarized in Table 2 .…”