Relationship between tumor recurrence and immunosuppressants after liver transplantation / 中华肝胆外科杂志

ABSTRACT

Objective:To clarify the relationship between postoperative tumor recurrence and the type and dosage of immunosuppressants in patients undergoing liver transplantation.Method:A retrospective analysis was conducted on the clinical data of patients who underwent liver transplantation for liver cancer from September 2007 to January 2019 at the Department of Hepatobiliary Surgery, First Affiliated Hospital of Chongqing Medical University. According to whether there was tumor recurrence after liver transplantation, the patients were divided into the case group and the control group. The etiology, alpha-fetoprotein level, Child-Pugh score, model for end-stage liver disease (MELD) score, and cancer nodules, number of tumors, diameter of largest cancer nodule, microvascular infiltration (MVI), large vessel infiltration, Edmondson grade of tumor differentiation, postoperative immunosuppression regimen, and blood trough concentration of tacrolimus or cyclosporine were compared between the two groups. The effects of calcineurin inhibitor (CNI) exposure in groups of patients on tumor recurrence were compared, and statistically significant factors were included in the Cox regression analysis. Using the BCLC staging standard of liver cancer, all the subjects were stratified, and the influence of CNI exposure on tumor recurrence was further analyzed.Results:This study included 50 patients. There were 15 patients in the case group, aged (45.8±8.2) years, with 13 males (86.7%). There were 35 patients in the control group, aged (45.4±12.0) years, 31 males (88.6%). The diameter of the largest cancer nodule in the case group was significantly larger than that in the control group [(5.9±3.0) cm vs (3.5±1.8) cm, P<0.05]. The tacrolimus exposure levels in the case group at 14 d after operation were significantly higher than the control group[(11.7±7.7)ng/ml vs (5.9±3.0)ng/ml, t=2.48], 1 month after operation [(12.2±4.5) ng/ml vs (7.8±4.3) ng/ml, t=2.82], 9 months after operation [(6.9±4.0) ng/ml to (4.7±2.0) ng/ml, t=2.21] and the area under the curve at 1 year after operation [(100.1±21.1) vs (74.4±19.2), t=3.66], all P<0.05. Survival analysis showed that the cumulative tumor-free survival rate of the CNI high-exposure group was significantly lower than that of the CNI low-exposure group (52.2% vs 85.2%, χ 2=6.52, P<0.05). Multivariate analysis using the Cox proportional hazards regression model showed that the largest cancer nodule diameter ( RR=1.23, 95% CI 1.01-1.60) and high CNI exposure ( RR=4.02, 95% CI 1.10-14.74) were independent risk factors for tumor recurrence after liver transplantation. Stratified analysis showed that of the 17 patients with BCLC stage B, 6 patients (66.7%) with high CNI exposure developed tumor recurrence, while only 1 patient (12.5%) with low CNI exposure developed tumor recurrence. The difference was statistically significant ( P<0.05). Survival analysis showed that the cumulative tumor-free survival rate of patients with CNI high-exposure was significantly lower than that of patients with CNI low-exposure (33.3% vs 87.5%, χ 2=5.74, P<0.05). Of the 8 patients with BCLC stage C, 4 patients developed tumor recurrence with CNI high-exposure (100.0%). There was no tumor recurrence in patients with low CNI exposure. The difference between groups was statistically significant ( P<0.05). Survival analysis showed that the cumulative tumor-free survival rate of patients with high CNI exposure was significantly lower than that of low CNI exposure (0 vs 100.0%, χ 2=6.80, P<0.05). Conclusions:Tumor recurrence after liver transplantation was not significantly related to the type of immunosuppressant used. High CNI exposure was a risk factor for tumor recurrence after liver transplantation.