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目的:探究肝癌行肝移植患者术后肿瘤复发与免疫抑制剂使用种类及剂量的关系。方法:回顾性分析重庆医科大学附属第一医院肝胆外科2007年9月至2019年1月因肝癌行肝移植患者临床资料。按肝移植术后肿瘤复发与否将患者分为病例组及对照组，对比两组患者的病因、甲胎蛋白水平、肝功能Child-Pugh评分、终末期肝病模型(MELD)评分、癌结节的数目、最大癌结节直径、微血管浸润(MVI)、大血管浸润、肿瘤分化Edmondson分级以及术后免疫抑制方案、他克莫司或环孢素血药谷浓度等。比较两组患者钙调神经磷酸酶抑制剂(CNI)暴露情况对肿瘤复发的影响，将有统计学意义的因素纳入Cox回归分析。按肝癌巴塞罗那(BCLC)分期标准对所有研究对象分层，进一步分析CNI暴露情况对肿瘤复发的影响。结果:共纳入50例患者，病例组15例，年龄(45.8±8.2)岁，男性13例(86.7%)。对照组35例，年龄(45.4±12.0)岁，男性31例(88.6%)。病例组最大癌结节直径大于对照组[(5.9±3.0)cm比(3.5±1.8)cm，n t＝2.84]，差异具有统计学意义(n P<0.05)。病例组术后14 d[(11.7±7.7)ng/ml比(5.9±3.0)ng/ml，n t＝2.48]、术后1个月[(12.2±4.5) ng/ml比(7.8±4.3) ng/ml，n t＝2.82]、术后9个月[(6.9±4.0) ng/ml比(4.7±2.0) ng/ml，n t＝2.21]及术后1年曲线下面积[(100.1±21.1)比(74.4±19.2)，n t＝3.66]的他克莫司暴露水平高于对照组，差异有统计学意义(n P<0.05)。生存分析显示，CNI高暴露组的累积无瘤生存率低于CNI低暴露组(52.2%比85.2%)，差异有统计学意义(χn 2＝6.52，n P<0.05)。Cox比例风险回归模型多因素分析显示最大癌结节直径(n RR＝1.23，95%n CI：1.01～1.60)、CNI高暴露(n RR＝4.02，95%n CI：1.10～14.74)为肝移植术后肿瘤复发的独立危险因素。分层分析显示，BCLC B期患者共17例，CNI高暴露下肿瘤复发6例(66.7%)，CNI低暴露时肿瘤复发1例(12.5%)，两者差异具有统计学意义(n P<0.05)，生存分析显示，CNI高暴露患者累积无瘤生存率低于CNI低暴露(33.3%比87.5%)，差异具有统计学意义(χn 2＝5.74，n P<0.05)；BCLC C期患者8例，CNI高暴露下肿瘤复发4例(100.0%)，CNI低暴露时无肿瘤复发，两者差异具有统计学意义(n P<0.05)，生存分析显示CNI高暴露累积无瘤生存率低于CNI低暴露(0比100.0%)，差异具有统计学意义(χn 2＝6.80，n P<0.05)。n 结论:肝移植术后肿瘤复发与免疫抑制剂使用种类无明显相关，CNI高暴露为肝移植术后肿瘤复发的危险因素。“,”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, n 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,n t=2.48], 1 month after operation [(12.2±4.5) ng/ml vs (7.8±4.3) ng/ml, n t=2.82], 9 months after operation [(6.9±4.0) ng/ml to (4.7±2.0) ng/ml, n t=2.21] and the area under the curve at 1 year after operation [(100.1±21.1) vs (74.4±19.2), n t=3.66], all n 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%, χn 2=6.52, n P<0.05). Multivariate analysis using the Cox proportional hazards regression model showed that the largest cancer nodule diameter (n RR=1.23, 95%n CI: 1.01-1.60) and high CNI exposure (n RR=4.02, 95%n 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 (n 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%, χn 2=5.74, n 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 (n 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%, χn 2=6.80, n P<0.05).n 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.