1Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Division of Transplant and Hepatobiliary Surgery, Henry Ford Transplant Institute, Henry Ford Hospital, Detroit, Michigan.
While experimental evidence has indicated that ischemia-reperfusion injury of the liver stimulates growth of micrometastases and adhesion of tumor cells, the clinical impact of ischemia-reperfusion injury on the recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) has not been fully investigated. To study this issue, we conducted a retrospective review of the medical records of 391 patients from two transplant centers who underwent LT for HCC. Ischemia times along with other tumor/recipient variables were analyzed as risk factors for recurrence of HCC. Subgroup analysis focused on patients with HCC who had pathologically proven vascular invasion because of the associated increased risk of micrometastasis. Recurrence occurred in 60 patients (15.3%) with median time to recurrence of 0.9 years (40days-4.6years). Cumulative recurrence curves according to CIT at 2hour intervals and WIT at 10min intervals showed that CIT>10hours and WIT>50min were associated with significantly increased recurrence (P=0.015 and 0.036, respectively). Multivariate Cox regression analysis identified prolonged cold (>10hours; P=0.03, hazard ratio [HR]=1.9) and warm (>50min; P=0.003, HR=2.84) ischemia times as independent risk factors for HCC recurrence, along with tumor factors including poor differentiation, micro- and macrovacular invasion, exceeding Milan criteria, and AFP>200ng/dl. Prolonged cold (P=0.04, HR=2.24) and warm (P=0.001, HR=5.1) ischemia times were also significantly associated with early (within 1yr) recurrence. In the subgroup analysis prolonged cold (P=0.01, HR=2.6) and warm (P=0.01, HR=3.23) ischemia times were independent risk factors for recurrence in patients with vascular invasion, whereas there was no association between ischemia times and HCC recurrence in patients with no vascular invasion. Conclusion: Reducing ischemia time may be a useful strategy to decrease HCC recurrence after LT, especially in those with other risk factors.