门静脉癌栓分型对肝细胞癌合并食管胃静脉曲张破裂出血患者再出血的影响
DOI: 10.12449/JCH260515
Impact of portal vein tumor thrombus classification on rebleeding in hepatocellular carcinoma patients with esophagogastric variceal bleeding
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摘要:
目的 通过观察肝细胞癌(HCC)合并不同分型门静脉癌栓(PVTT)及食管胃静脉曲张破裂出血(EGVB)患者的再出血情况,探讨PVTT分型对再出血的影响,为制订此类患者的合理治疗方案提供参考。 方法 回顾性纳入2020年7月—2025年1月因EGVB于首都医科大学附属北京地坛医院就诊的130例HCC合并PVTT患者为研究对象,根据是否接受内镜治疗将患者分为内镜治疗组(n=97)和保守治疗组(n=33)。收集患者人口学及临床资料,比较两组止血成功率及再出血情况。符合正态分布的计量资料组间比较采用成组t检验,不符合正态分布的计量资料组间比较采用Mann-Whitney U检验;计数资料组间比较采用χ2检验或Fisher’s精确检验。采用Kaplan-Meier法估计不同分型PVTT患者的再出血累积发生率。通过倾向性评分匹配(PSM)对内镜治疗组和保守治疗组进行配对,以均衡两组患者基线数据。采用Cox比例风险模型进行单因素和多因素分析,筛选再出血的独立危险因素。 结果 内镜治疗组患者的6个月内累积再出血率显著低于保守治疗组[35.1% vs 57.6%,风险比(HR)=0.480,95%置信区间(95%CI):0.272~0.851,P=0.019]。PVTT Ⅲ~Ⅳ组患者的6个月累积再出血率显著高于PVTT Ⅱ组(52.2% vs 37.5%,HR=1.744,95%CI:1.008~3.018, P=0.022)。PSM后,内镜治疗组和保守治疗组的再出血率差异无统计学意义(38.1% vs 14.3%,HR=1.500,95%CI:0.125~2.002,P=0.588),但PVTT Ⅲ~Ⅳ组患者的累积再出血率显著高于PVTT Ⅱ组(58.8% vs 12.5%,HR=1.561,95%CI:1.195~12.499,P=0.033)。多因素Cox回归分析显示,PVTT分型(HR=1.412,95%CI:0.998~1.997,P=0.049)、血小板计数(HR=1.006,95%CI:1.001~1.010,P=0.021)、C反应蛋白(HR=1.011,95%CI:1.001~1.021,P=0.026)和腹水(HR=1.803,95%CI:1.059~3.068,P=0.030)是再出血的独立危险因素。 结论 对于HCC合并PVTT及EGVB患者,内镜治疗可成功止血,但未能显著降低再出血率;PVTT分型影响再出血风险,其中PVTT Ⅲ~Ⅳ型患者再出血率较高。 Abstract:Objective To investigate the impact of portal vein tumor thrombus (PVTT) classification on rebleeding in hepatocellular carcinoma (HCC) patients with different PVTT subtypes and esophagogastric variceal bleeding (EGVB), and to provide a reference for formulating rational treatment regimens for such patients. Methods A retrospective study was performed for 130 patients with HCC and PVTT who were treated due to EGVB in Beijing Ditan Hospital, Capital Medical University, from July 2020 to January 2025, and according to whether endoscopic treatment was performed, the patients were divided into endoscopic treatment group with 97 patients and conservative treatment group with 33 patients. Demographic and clinical data were collected from all patients, and the two groups were compared in terms of hemostasis success rate and rebleeding rate. The independent-samples t test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to estimate the cumulative incidence rate of rebleeding in patients with different subtypes of PVTT. Propensity score matching (PSM) was performed for the endoscopic treatment group and the conservative treatment group to balance the baseline data of the two groups. The Cox proportional hazards model was used to perform univariate and multivariate analyses and identify independent risk factors for rebleeding. Results The endoscopic treatment group had a significantly lower cumulative rebleeding rate within 6 months than the conservative treatment group (35.1% vs 57.6%, hazard ratio [HR]=0.480, 95% confidence interval [CI]: 0.272—0.851, P=0.019). The PVTT Ⅲ—Ⅳ group had a significantly higher cumulative rebleeding rate within 6 months than the PVTT Ⅱ group (52.2% vs 37.5%, HR=1.744, 95%CI: 1.008 — 3.018, P=0.022). After PSM, there was no significant difference in rebleeding rate between the endoscopic treatment group and the conservative treatment group (38.1% vs 14.3%,HR=1.500,95%CI:0.125 — 2.002, P=0.588), while the PVTT Ⅲ—Ⅳ group had a significantly higher cumulative rebleeding rate than the PVTT Ⅱ group (58.8% vs 12.5%,HR=1.561,95%CI:1.195 — 12.499,P=0.033). The multivariate Cox regression analysis showed that PVTT subtype (HR=1.412, 95%CI: 0.998 — 1.997, P=0.049), platelet count (HR=1.006, 95%CI: 1.001 — 1.010, P=0.021), C-reactive protein (HR=1.011, 95%CI: 1.001 — 1.021, P=0.026), and ascites (HR=1.803, 95%CI: 1.059 — 3.068, P=0.030) were independent risk factors for rebleeding. Conclusion For HCC patients with PVTT and EGVB, endoscopic treatment can successfully achieve hemostasis, while it fails to significantly reduce rebleeding rates. PVTT classification can affect the risk of rebleeding, and patients with PVTT types Ⅲ—Ⅳ have a relatively high rebleeding rate. -
表 1 2组患者基线数据比较
Table 1. Baseline data of the patients
项目 内镜治疗组
(n=97)保守治疗组
(n=33)统计值 P值 匹配后内镜
治疗组(n=21)匹配后保守
治疗组(n=21)统计值 P值 年龄(岁) 57.7±9.8 57.2±10.5 t=0.263 0.609 56.6±9.1 57.6±7.2 t=0.462 0.501 性别[例(%)] χ2=2.012 0.241 0.606 男 86(88.7) 26(78.8) 18(85.7) 20(95.2) 女 11(11.3) 7(21.2) 3(14.3) 1(4.8) 病因控制[例(%)] χ2=0.208 0.685 χ2=0.404 0.525 是 41(42.3) 15(45.5) 12(57.1) 14(66.7) 否 56(57.7) 18(54.5) 9(42.9) 7(33.3) 肝病病因[例(%)] 0.893 0.875 乙型肝炎 50(51.5) 17(51.5) 11(52.4) 10(47.6) 丙型肝炎 12(12.4) 4(12.1) 2(9.5) 3(14.3) 酒精性肝病 8(8.2) 5(15.2) 2(9.5) 3(14.3) 自身免疫性肝病 10(10.3) 2(6.1) 2(9.5) 1(4.8) 胆汁淤积性肝病 3(3.1) 1(3.0) 0(0.0) 2(9.5) 其他 14(14.4) 4(12.1) 4(19.1) 2(9.5) 合并急性感染[例(%)] 0.738 1.000 是 9(9.3) 4(12.1) 1(4.8) 1(4.8) 否 88(90.7) 29(87.9) 20(95.2) 20(95.2) 肿瘤干预[例(%)] χ2=3.565 0.168 χ2=3.500 0.174 无 30(30.9) 6(18.1) 6(28.6) 10(47.6) 单一治疗 21(21.6) 12(36.4) 12(57.1) 6(28.6) 多种方法综合治疗 46(47.4) 15(45.5) 3(14.3) 5(23.8) 中性粒细胞(×109/L) 4.1(1.8~4.9) 4.8(2.9~4.1) Z=-2.926 0.003 3.3(1.8~5.6) 2.9(2.2~4.0) Z<0.001 1.000 血小板计数(×109/L) 99.2(59.5~119.0) 112.2(69.0~150.1) Z=-1.461 0.144 89.0(41.0~89.0) 90.0(48.0~90.0) Z=-0.655 0.513 血红蛋白(g/L) 90.4±24.2 88.9±26.4 t=0.357 0.552 85.7±23.5 84.9±22.7 t=0.252 0.615 ALT(U/L) 53.1(21.3~53.4) 84.2(31.7~114.7) Z=-2.600 0.009 40.0(26.8~85.0) 52.1(38.3~200.4) Z=-1.158 0.247 AST(U/L) 95.1(33.4~106.6) 159.5(51.4~177.8) Z=-3.140 0.002 87.6(47.6~107.9) 93.3(67.9~258.4) Z=-1.762 0.078 总胆红素(μmol/L) 36.0(16.4~36.3) 99.6(20.6~87.9) Z=-3.349 0.001 55.9(13.6~70.6) 24.7(20.8~34.5) Z=-0.906 0.365 白蛋白(g/L) 31.2(28.2~34.2) 31.6(27.3~35.4) Z=-1.115 0.909 30.3(25.4~35.3) 27.7(25.6~32.1) Z=-1.410 0.159 肌酐(μmol/L) 74.4(58.5~85.4) 86.2(61.5~87.2) Z=-0.930 0.352 65.2(60.6~82.1) 76.3(59.4~85.1) Z=-0.554 0.580 国际标准化比值 1.4(1.2~1.5) 1.6(1.3~1.6) Z=-1.896 0.058 1.5(1.3~1.6) 1.6(1.3~1.9) Z=-0.466 0.641 AFP(ng/mL) 254.5
(10.8~2 000.0)878.0
(142.0~2 000.0)Z=-0.638 0.523 1 115.0
(9.5~2 000.0)421.0
(128.0~2 000.0)Z=-0.073 0.501 C反应蛋白(mg/L) 26.2
(5.4~39.7)59.1
(14.8~77.5)Z=-3.469 0.001 12.3(4.8~40.6) 27.2(10.9~72.1) Z=-1.511 0.131 血钠(mmol/L) 133.3
(134.3~140.2)137.1
(133.9~141.1)Z=-0.202 0.840 140.2
(134.5~142.2)135.2
(131.8~138.2)Z=-1.763 0.078 合并肝硬化[例(%)] 95(97.9) 31(94.0) χ2=2.763 0.158 19(90.5) 19(90.5) χ2=0.000 1.000 合并腹水[例(%)] 68(70.1) 27(81.8) χ2=1.718 0.190 12(57.1) 16(76.2) χ2=1.714 0.190 合并肝性脑病[例(%)] 22(22.7) 17(51.5) χ2=9.749 0.002 6(28.6) 4(19.0) 0.719 首次出血[例(%)] χ2=1.315 0.252 0.469 是 55(56.7) 22(66.7) 6(28.6) 4(19.1) 否 42(43.3) 11(33.3) 15(71.4) 17(80.9) Table . (continued)
项目 内镜治疗组
(n=97)保守治疗组
(n=33)统计值 P值 匹配后内镜
治疗组(n=21)匹配后保守
治疗组(n=21)统计值 P值 PVTT分型(程氏分型)
[例(%)]χ2=3.104 0.212 χ2=5.700 0.058 Ⅱ型 30(30.9) 10(30.3) 5(23.8) 3(14.3) Ⅲ型 10(10.3) 3(9.1) 4(19.1) 0(0.0) Ⅳ型 57(58.8) 20(60.6) 12(57.1) 18(85.7) 肿瘤BCLC分期
[例(%)]χ2=12.912 0.001 χ2=0.429 0.513 C期 74(76.3) 14(42.4) 13(61.9) 15(71.4) D期 23(23.7) 19(57.6) 8(38.1) 6(28.6) 蔡尔德-皮尤分级
[例(%)]χ2=9.417 0.009 χ2=0.963 0.618 A级 20(20.6) 5(15.1) 7(33.3) 6(28.6) B级 65(67.0) 16(48.5) 6(28.6) 9(42.8) C级 12(12.4) 12(36.4) 8(38.1) 6(28.6) 再出血时间(d) 55(23~168) 28(8~78) Z=-2.141 0.032 9(9~27) 42(9~60) Z=-1.361 0.174 注:PVTT,门静脉癌栓;BCLC,巴塞罗那肝癌临床分期;ALT,丙氨酸氨基转移酶;AST,天冬氨酸氨基转移酶;AFP,甲胎蛋白。
表 2 PVTT合并EGVB患者再出血的危险因素分析
Table 2. Risk factors of rebleeding in patients with PVTT and EGVB
变量 单因素分析 多因素分析 HR(95%CI) P值 HR(95%CI) P值 肿瘤干预 3.450(1.598~7.447) 0.002 0.700(0.485~1.010) 0.057 内镜治疗 2.350(1.123~4.918) 0.023 0.911(0.371~2.235) 0.838 血小板计数 1.006(1.001~1.011) 0.010 1.006(1.001~1.010) 0.021 ALT 1.008(1.003~1.012) 0.001 1.004(0.996~1.013) 0.272 AST 1.003(1.001~1.005) 0.003 0.998(0.994~1.013) 0.202 总胆红素 1.005(1.001~1.009) 0.009 1.000(0.994~1.007) 0.898 C反应蛋白 1.011(1.005~1.017) <0.001 1.011(1.001~1.021) 0.026 BCLC分期 0.237(0.115~0.486) <0.001 0.997(0.449~2.217) 0.995 PVTT分型 1.553(1.005~2.402) 0.048 1.412(0.998~1.997) 0.049 腹水 1.644(1.033~2.618) 0.036 1.803(1.059~3.068) 0.030 肝性脑病 2.165(1.256~3.732) 0.005 1.359(0.727~2.540) 0.337 蔡尔德-皮尤分级 1.206(1.032~1.410) 0.019 0.985(0.482~2.012) 0.966 注:PVTT,门静脉癌栓;EGVB,食管胃静脉曲张破裂出血;ALT,丙氨酸氨基转移酶;AST,天冬氨酸氨基转移酶;BCLC,巴塞罗那肝癌临床分期;HR,风险比;CI,置信区间。
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