Role of the criteria based on preoperative serological indexes of AFP and GGT in predicting long-term survival of patients with hepatocellular carcinoma after liver transplantation
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摘要:
目的 分析术前血清学指标对肝细胞癌(HCC)患者肝移植术后长期生存和肿瘤复发的预测作用,探索其对扩大米兰标准的意义。 方法 回顾性分析669例HCC肝移植受者的临床资料,采用受试者工作特征(ROC)曲线计算最佳截取值,采用单因素和多因素回归分析影响HCC患者肝移植术后总生存率和无复发生存率的危险因素,分析术前血清肝酶与肿瘤病理学特征的相关性,比较甲胎蛋白(AFP)联合γ-谷氨酰转移酶(GGT)以及不同肝移植标准对HCC患者肝移植术后生存和复发的预测价值。 结果 超米兰标准、肿瘤直径之和(TTD) > 8 cm、AFP > 200 ng/mL和GGT > 84 U/L是影响HCC患者肝移植术后总生存率和无复发生存率的独立危险因素(均为P < 0.05)。相关性分析结果显示,术前血清GGT水平与TTD,肿瘤数量,静脉侵犯,微卫星病变,包膜侵犯,肿瘤、淋巴结、转移(TNM)分期,Child-Pugh评分,超米兰标准均存在相关性(均为P < 0.05)。将米兰标准、TTD与血清肝酶指标(AFP和GGT)结合,提出Milan-AFP-GGT-TTD(M-AGT)标准。符合M-AGT标准者(其中111例超米兰标准)术后5年总生存率和无复发生存率均高于符合杭州标准者(均为P < 0.05),与符合加州大学旧金山分校(UCSF)标准者的术后5年总生存率和无复发生存率比较差异均无统计学意义(均为P > 0.05)。 结论 术前血清学指标AFP和GGT可有效预测HCC患者肝移植术后长期生存和肿瘤复发,建立基于血清学指标的M-AGT标准有助于补充米兰标准,且简单易行。 -
关键词:
- 肝细胞癌 /
- 米兰标准 /
- 杭州标准 /
- γ-谷氨酰转移酶(GGT) /
- 甲胎蛋白(AFP) /
- 肿瘤直径之和(TTD) /
- 总生存率 /
- 无复发生存率
Abstract:Objective To evaluate the role of preoperative serological indexes in predicting long-term survival and tumor recurrence of hepatocellular carcinoma (HCC) patients after liver transplantation, aiming to explore its significance in expanding the Milan criteria. Methods Clinical data of 669 recipients undergoing liver transplantation for HCC were retrospectively analyzed. The optimal cut-off value was calculated by the receiver operating characteristic (ROC) curve. The risk factors affecting the overall survival and recurrence-free survival rates of HCC patients after liver transplantation were identified by univariate and multivariate regression analyses. The correlation between preoperative serum liver enzymes and pathological characteristics in HCC patients was analyzed. The predictive values of alpha-fetoprotein (AFP) combined with γ -glutamyl transferase (GGT) and different liver transplant criteria for the survival and recurrence of HCC patients after liver transplantation were compared. Results Exceeded Milan criteria, total tumor diameter (TTD) > 8 cm, AFP > 200 ng/mL and GGT > 84 U/L were the independent risk factors for the overall survival and recurrence-free survival rates of HCC patients after liver transplantation (all P < 0.05). Correlation analysis showed that preoperative serum GGT level was correlated with TTD, number of tumor, venous invasion, microsatellite lesions, capsular invasion, tumor, node, metastasis (TNM) stage, Child-Pugh score and exceeded Milan criteria (all P < 0.05). Milan-AFP-GGT-TTD (M-AGT) criteria were proposed by combining Milan criteria, TTD with serum liver enzyme indexes (AFP and GGT). The 5-year overall survival and recurrence-free survival rates of HCC recipients who met the M-AGT criteria (111 cases of exceeded Milan criteria) were significantly higher than those who met Hangzhou criteria (both P < 0.05), whereas had no significant difference from their counterparts who met the University of California at San Francisco (UCSF) criteria (both P > 0.05). Conclusions Preoperative serological indexes of AFP and GGT could effectively predict the long-term survival and tumor recurrence of HCC patients after liver transplantation. Establishing the M-AGT criteria based on serological indexes contributes to expanding the Milan criteria, which is convenient and feasible. -
表 1 肝移植术后生存和复发危险因素的单因素分析
Table 1. Univariate analysis of risk factors for survival and recurrence after liver transplantation
变量 n 总生存率(%) P值 无复发生存率(%) P值 1年 3年 5年 7年 1年 3年 5年 7年 性别 0.233 0.227 男 618 88 72 68 65 77 66 63 62 女 51 90 80 80 77 78 76 76 73 年龄 0.566 0.770 < 40岁 81 87 78 73 68 83 72 69 64 40~49岁 246 88 68 65 64 75 65 62 62 50~59岁 247 88 74 70 66 78 67 64 62 > 60岁 95 86 76 73 70 76 69 68 68 GGT < 0.001 < 0.001 ≤84 U/L 371 92 85 82 81 87 81 78 78 > 84 U/L 298 82 57 53 48 64 50 47 45 AST < 0.001 < 0.001 ≤63 U/L 402 92 82 80 77 84 76 74 74 > 63 U/L 267 82 60 54 51 66 55 50 48 ALT < 0.001 < 0.001 ≤56 U/L 414 90 79 77 75 82 74 72 72 > 56 U/L 255 85 63 56 52 69 57 52 50 AFP < 0.001 < 0.001 ≤200 ng/mL 470 91 80 78 75 85 76 74 72 > 200 ng/mL 199 80 54 46 43 58 46 41 40 HBV DNA 0.225 0.525 ≤1 copies/mL 460 88 71 66 65 77 66 63 62 > 1 copies/mL 209 88 76 74 69 78 69 67 65 微卫星病变 0.002 0.001 否 466 89 76 73 70 80 71 68 67 是 203 85 65 58 56 69 58 55 53 静脉侵犯 < 0.001 < 0.001 否 582 90 78 74 71 81 72 69 68 是 87 73 39 37 33 50 33 33 30 包膜侵犯 0.143 0.034 否 574 88 74 71 68 78 69 66 65 是 95 87 64 57 57 69 55 55 55 TNM分期 < 0.001 < 0.001 1 307 90 81 77 75 85 77 73 72 2 191 90 71 68 67 77 64 62 61 3 129 81 56 52 43 59 51 47 45 4~6 42 85 69 65 65 73 62 62 62 Child-Pugh评分 0.649 0.491 ≤6分 306 88 73 69 64 78 65 63 61 7~9分 223 89 75 70 70 78 71 68 67 > 9分 140 86 70 66 65 74 65 62 62 MELD评分 0.094 0.202 ≤15分 507 89 74 71 67 78 68 66 64 > 15分 162 85 69 64 63 75 64 61 60 肿瘤数目 < 0.001 < 0.001 单个 398 91 79 77 74 84 76 73 72 多个 271 84 63 57 54 67 54 51 51 TTD < 0.001 < 0.001 ≤8 cm 541 92 81 78 75 84 76 73 72 > 8 cm 128 72 38 33 28 46 31 29 27 组织学分化 0.526 0.305 高 30 87 80 76 70 77 66 66 66 中 558 89 73 69 66 78 68 65 64 低 81 84 67 65 65 68 60 58 58 米兰标准 < 0.001 < 0.001 符合 357 95 91 89 87 91 87 85 84 不符合 312 80 52 45 42 61 45 41 40 杭州标准 < 0.001 < 0.001 符合 605 90 78 75 72 82 73 70 68 不符合 64 65 20 16 16 28 13 13 13 UCSF标准 < 0.001 < 0.001 符合 398 94 90 87 85 90 85 83 82 不符合 271 79 48 42 38 59 41 37 35 表 2 HCC肝移植术后总生存率危险因素的多因素分析
Table 2. Multivariate analysis of the risk factors for overall survival rate after liver transplantation for HCC
变量 回归系数 标准误 Wald χ2值 HR① 95% CI② P值 超米兰标准 1.277 0.198 41.566 3.585 2.432~5.286 < 0.001 TTD > 8 cm 0.559 0.158 12.609 1.749 1.285~2.382 < 0.001 AFP > 200 ng/mL 0.478 0.147 10.600 1.613 1.210~2.152 0.001 GGT > 84 U/L 0.473 0.161 8.583 1.605 1.170~2.202 0.003 AST > 63 U/L 0.561 0.149 14.209 1.753 1.309~2.347 < 0.001 注:① HR为风险比。
② CI为可信区间。表 3 HCC肝移植术后无复发生存率危险因素的多因素分析
Table 3. Multivariate analysis of the risk factors for recurrence-free survival rate after liver transplantation for HCC
变量 回归系数 标准误 Wald χ2值 HR① 95%CI② P值 超米兰标准 1.125 0.177 40.201 3.080 2.175~4.361 < 0.001 TTD > 8 cm 0.564 0.151 14.010 1.758 1.308~2.362 < 0.001 AFP > 200 ng/mL 0.616 0.137 20.372 1.852 1.417~2.420 < 0.001 GGT > 84 U/L 0.511 0.152 11.357 1.667 1.238~2.245 0.001 ALT > 56 U/L 0.365 0.135 7.326 1.441 1.106~1.877 0.007 注:① HR为风险比。
② CI为可信区间。表 4 超米兰标准患者中不同肝移植标准的总生存率和无复发生存率比较
Table 4. Comparison of overall survival and recurrence-free survival rates of different liver transplant criteria in patients exceeded Milan criteria
肝移植标准名称 n 总生存率(%) P值 无复发生存率(%) P值 1年 3年 5年 7年 1年 3年 5年 7年 M-AGT标准 111 85 71 64 61 74 63 58 58 杭州标准 249 84 60 53 49 0.075 69 53 48 46 0.092 UCSF标准 65 88 81 71 68 0.315 78 72 68 65 0.327 -
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