内镜治疗肝细胞癌合并门静脉癌栓患者食管胃静脉曲张出血后再出血的危险因素分析

梁秀霞; 何玲玲; 杨君茹; 张福阳; 马佳丽; 周玉玲; 胡居龙; 李坪; 魏红山

doi:10.3969/j.issn.1001-5256.2022.10.017

内镜治疗肝细胞癌合并门静脉癌栓患者食管胃静脉曲张出血后再出血的危险因素分析

DOI: 10.3969/j.issn.1001-5256.2022.10.017

首都医科大学附属北京地坛医院消化内科，北京 100015

基金项目:

国家自然科学基金 (82170541);

北京市医院管理中心消化内科学科协同发展中心专项 (XXZ0404);

首都医科大学科研培育基金 (PYZ20031)

伦理学声明：本研究于2018年4月26日经由首都医科大学附属北京地坛医院伦理委员会审核通过，批号：201802101。

利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。

作者贡献声明：梁秀霞、何玲玲、魏红山负责课题设计，资料分析和撰写论文；梁秀霞、何玲玲、杨君茹、张福阳、马佳丽、周玉玲、胡居龙负责收集及分析数据；魏红山、李坪指导撰写文章并最后定稿。

详细信息

通信作者:
魏红山，drwei@ccmu.edu.cn

作者说明：梁秀霞、何玲玲对本文贡献等同，同为第一作者

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出版历程
- 收稿日期: 2022-03-09
- 录用日期: 2022-06-06
- 出版日期: 2022-10-20

Risk factors of rebleeding after endoscopic treatment of patients with portal vein tumor thrombus and esophagogastric variceal bleeding

Department of Gastroenterology, Beijing Ditan Hospital, The Capital Medical University, Beijing 100015, China

Research funding:

National Natural Science Foundation of China (82170541);

Digestive Medical Coordinated Development Center of Beijing Municipal Administration of Hospitals (XXZ0404);

Natural Science Foundation of Capital Medical University (PYZ20031)

More Information

Corresponding author: WEI Hongshan, drwei@ccmu.edu.cn(ORCID: 0000-0001-8893-653X)

摘要

摘要: 目的探讨合并门静脉癌栓(PVTT)的肝细胞癌(HCC)患者经内镜下治疗食管胃静脉曲张出血(EVB)后再出血的危险因素。方法回顾性分析2008年9月—2016年12月首都医科大学附属北京地坛医院消化内科收治的169例乙型肝炎相关HCC伴PVTT合并EVB经内镜治疗的患者资料，其中47例为PVTT Ⅱ型，67例为PVTT Ⅲ型，55例为PVTT Ⅳ型。比较不同PVTT分型患者的临床指标差异，计量资料多组间比较采用方差分析或Kruskal-Wallis H检验；计数资料组间比较采用χ²检验或校正Fisher检验。采用Kaplan-Meier方法绘制再出血及生存曲线，采用Log-rank检验法比较再出血率和生存率。采用Cox单因素和多因素分析影响患者1年再出血的危险因素。结果在不同PVTT分型患者的各项临床指标比较中，PVTT Ⅳ型比PVTT Ⅱ、Ⅲ型患者的直接胆红素水平更高(Z=6.153，P=0.046)。所有患者经内镜下治疗后均可成功止血，PVTT Ⅱ型、PVTT Ⅲ型、PVTT Ⅳ型患者的半年、1年的再出血率无显著差异，不同分型患者半年、1年、2年、3年的累积生存率无显著差异(P值均＞0.05)。Cox多因素分析显示合并肝性脑病(HR=3.643, 95%CI：2.099~6.325，P＜0.001)、GGT(HR=1.002, 95%CI：1.000~1.005，P=0.029)、AFP(HR=1.000, 95%CI：1.000~1.000，P=0.002)、肿瘤个数(HR=1.647, 95%CI：1.011~2.684，P=0.045)是影响PVTT合并EVB患者内镜治疗后1年内再出血的危险因素。结论伴有PVTT的HCC患者合并EVB可行内镜下止血治疗，不同PVTT分型的患者再出血率及生存率无显著差异。合并肝性脑病、γ-谷氨酰基移换酶、甲胎蛋白、肿瘤个数是影响PVTT合并EVB患者内镜治疗后1年再出血的独立危险因素。
- 癌，肝细胞 /
- 门静脉 /
- 食管和胃静脉曲张 /
- 内窥镜 /
- 治疗学 /
- 出血
Abstract: Objective To analyze the rebleeding rate in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) after endoscopic treatment of esophagogastric variceal bleeding and then assessed the risk factors of the rebleeding in the patients. Methods This study retrospectively recruited 169 hepatitis B-associated HCC patients complicated with PVTT and esophagogastric variceal bleeding treated by endoscopy in Department of Gastroenterology, Beijing Ditan Hospital from September 2008 to December 2016. Among them, 47 patients had PVTT Ⅱ, 67 patients had PVTT Ⅲ, and 55 patients had PVTT Ⅳ. Their clinicopathological and follow-up data were retrieved from the medical records and statistically analyzed. Continuous data were compared among groups using ANOVA or Kruskal-Wallis H test. Categorial data were compared among groups using Chi-square test or corrected Fisher test. The Kaplan-Meier curves and Log-rank test were performed to analyze the rebleeding rate and cumulative survival rates after treatment. The univariate multivariate Cox regression analyses were used to identify the risk factors affecting the rebleeding of patients. Results Compared with PVTT Ⅱ and Ⅲ, PVTT Ⅳ patients had a higher serum level of the direct bilirubin (Z=6.153, P=0.046). The endoscopy treatment successfully blocked esophagogastric variceal bleeding in all patients. There was no significant difference in the rebleeding rates within six months and a year after the treatment (all P > 0.05). It was also no statistically significant difference in cumulative survival rates in six months and l-, 2-, and 3-year after the treatment in PVTT Ⅱ, Ⅲ, and Ⅳ patients (all P > 0.05). Cox multivariate regression analysis showed that hepatic encephalopathy (HR=3.643, 95%CI: 2.099-6.325, P < 0.001), γ-glutamyltransferase (HR=1.002, 95%CI: 1.000-1.005, P=0.029), AFP (HR=1.000, 95%CI: 1.000-1.000, P=0.002) and numbers of tumor lesions (HR=1.647, 95%CI: 1.011-2.684, P=0.045) were all independent risk factors for 1-year rebleeding in these PVTT patients with esophagogastric variceal bleeding after endoscopic treatment. Conclusion Endoscopic hemostasis is a feasible treatment option for HCC patients with PVTT and esophagogastric variceal bleeding. However, there was no significant difference in the rebleeding and cumulative survival rates in these patients. Furthermore, hepatic encephalopathy, γ-glutamyltransferase, AFP and numbers of tumor lesions were all independent risk factors for 1-year rebleeding in these patients.
- Carcinoma, Hepatocellular /
- Portal Vein /
- Esophageal and Gastric Varices /
- Endoscopes /
- Therapeutics /
- Hemorrhage

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图 1 不同PVTT分型患者再出血情况

注：a，半年再出血分析；b，1年再出血分析。

Figure 1. Rebleeding in patients with different types of portal vein tumor thrombus

下载: 全尺寸图片幻灯片

图 2 不同PVTT分型患者生存情况

注：a，半年生存分析；b，1年生存分析；c，2年生存分析；d，3年生存分析。

Figure 2. Survival of patients with different types of portal vein tumor thrombus

下载: 全尺寸图片幻灯片

表 1 基线特征

Table 1. Baseline Characteristics

指标	PVTT Ⅱ型 (n=47)	PVTT Ⅲ型 (n=67)	PVTT Ⅳ型 (n=55)	统计值	P值
年龄(年)	54.9±11.7	52.7±11.1	50.8±10.4	F=1.761	0.175
男性[例(%)]	42(89.4)	56(83.6)	47(85.5)	χ²=0.765	0.682
合并肝性脑病[例(%)]	6(12.8)	13(19.4)	9(16.4)	χ²=0.883	0.643
合并腹水[例(%)]	41(87.2)	63(94.0)	53(96.4)	χ²=3.417	0.181
门静脉直径(mm)	13(12~15)	15(13~19)	16(12~20)	Z=4.368	0.113
脾脏厚度(mm)	48(45~55)	53(45~58)	50(44~55)	Z=2.739	0.254
白细胞(×10⁹/L)	3.0(4.7~7.3)	5.5(3.7~8.0)	5.5(3.5~7.1)	Z=0.881	0.644
血红蛋白(g/L)	98.4±25.0	94.1±24.6	89.8±23.5	F=1.542	0.217
血小板计数(×10⁹/L)	86.0(56.7~148.0)	89.6(64.4~121.0)	97.9(67.4~138.0)	Z=0.288	0.866
ALT (U/L)	31.2(21.0~48.1)	40.9(27.6~55.2)	35.6(23.9~71.6)	Z=3.576	0.167
总胆红素(μmol/L)	19.7(14.2~34.8)	23.7(16.1~34.3)	30.0(19.1~49.9)	Z=5.216	0.074
直接胆红素(μmol/L)	9.4(6.4~16.6)	11.0(7.2~18.8)	14.3(8.3~29.4)	Z=6.153	0.046
白蛋白(g/L)	33.1±4.7	31.2±5.2	31.1±5.5	F=2.255	0.108
GGT(U/L)	75.2(39.5~162.4)	96.4(43.4~198.6)	160.7(52.9~261.8)	Z=4.337	0.114
肌酐(μmol/L)	62.3(56.0~73.3)	66.3(58.4~78.0)	64.1(58.0~76.7)	Z=0.908	0.635
凝血酶原时间(s)	14.6(13.4~15.9)	14.6(13.7~16.4)	14.6(13.8~16.1)	Z=0.834	0.659
国际标准化比值	1.2(1.2~1.3)	1.3(1.2~1.4)	1.2(1.2~1.4)	Z=1.053	0.591
AFP (ng/mL)	36.6(6.5~367.5)	25.3(6.7~255.1)	39.0(7.4~290.1)	Z=0.127	0.939
Child-Pugh分级(A/B/C，例)	7/31/9	6/37/24	1/34/20	χ²=8.946	0.062
MELD评分	6.1(3.3~10.0)	7.7(5.1~11.0)	8.2(4.5~11.8)	Z=3.816	0.148

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表 2 PVTT合并食管胃底静脉曲张出血患者1年再出血影响因素

Table 2. Influence factors of 1-year rebleeding in patients with PVTT complicated with esophagogastric variceal hemorrhage

参数	单因素分析 HR(95%CI)	P值
年龄(年)	1.013(0.963~1.065)	0.621
男性	2.246(0.718~7.025)	0.164
PVTT分型	0.602(0.306~1.182)	0.140
合并肝性脑病	5.778(2.332~14.317)	＜0.001
合并腹水	1.007(0.289~3.506)	0.991
门静脉直径(mm)	0.987(0.929~1.048)	0.661
脾脏厚度(mm)	1.001(0.971~1.032)	0.939
白细胞(×10⁹/L)	0.825(0.629~1.083)	0.166
血红蛋白(g/L)	0.994(0.963~1.025)	0.694
血小板计数(×10⁹/L)	0.999(0.987~1.011)	0.877
ALT(U/L)	0.991(0.974~1.009)	0.316
总胆红素(μmol/L)	0.927(0.823~1.043)	0.209
直接胆红素(μmol/L)	1.386(1.046~1.836)	0.023
白蛋白(g/L)	1.017(0.891~1.161)	0.802
GGT(U/L)	1.006(1.002~1.010)	0.006
肌酐(μmol/L)	0.982(0.943~1.023)	0.390
凝血酶原时间(s)	0.323(0.118~0.881)	0.027
AFP(ng/ml)	1.000(1.000~1.000)	＜0.001
Child-Pugh分级	1.363(0.269~6.914)	0.708
MELD评分	1.171(0.814~1.684)	0.394
CNLC分期	1.229(0.456~3.314)	0.684
体力状态评分	0.588(0.121~2.858)	0.511
肿瘤肝外转移	0.566(0.146~2.190)	0.409
肿瘤大小	1.066(0.894~1.271)	0.476
肿瘤个数	2.364(1.147~4.871)	0.020

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