肝硬化重度食管胃静脉曲张治疗后再出血及5年预后影响因素分析

曹影影; 韩涛; 张钰; 刘芳; 梁静; 袁海霞; 李隽; 向慧玲

doi:10.3969/j.issn.1001-5256.2021.06.022

肝硬化重度食管胃静脉曲张治疗后再出血及5年预后影响因素分析

DOI: 10.3969/j.issn.1001-5256.2021.06.022

天津医科大学第三中心临床学院，天津市第三中心医院消化肝病科，天津市肝胆疾病研究所；天津市人工细胞工程技术研究中心，天津 300170

基金项目:

国家科技重大专项 (2017ZX10203201-007);

国家科技重大专项 (2017ZX10203202-04);

天津市科技计划项目 (19ZXDBSY00030)

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：曹影影实施研究，资料分析，撰写论文；张钰、刘芳、梁静、李隽、袁海霞、向慧玲实施研究，拟定写作思路，统计指导；韩涛课题设计，文章审阅。

详细信息

作者简介:
曹影影(1990—)，女，主要从事肝脏疾病研究

通信作者:
韩涛，hantaomd@126.com

中图分类号: R575.2
计量
- 文章访问数: 561
- HTML全文浏览量: 386
- PDF下载量: 61
- 被引次数: 0
出版历程
- 收稿日期: 2020-11-14
- 录用日期: 2020-12-22
- 出版日期: 2021-06-20

Rebleeding and prognosis of patients with liver cirrhosis and severe esophagogastric variceal bleeding

Third Central Clinical College, Tianjin Medical University; Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital; Tianjin Institute of Hepatobiliary Disease; Artificial Cell Engineering Technology Research Center, Tianjin 300170, China

摘要

摘要: 目的探讨肝硬化并发重度食管胃静脉曲张破裂出血(EVB)患者5年内再出血的危险因素及影响其5年生存的相关因素。方法回顾性选取2012年5月—2014年5月因重度首次EVB于天津市第三中心医院就诊的肝硬化129例患者，随访时间为5年。分析患者年龄、性别、肝硬化原因、首次出血时是否合并感染、肝硬度(LSM)、脾硬度(SSM)、门静脉内径、生化学指标、再出血时间及预后等临床资料。以食管胃静脉曲张再出血为主要研究终点，以死亡为次要研究终点。计量资料2组间比较采用t检验；计数资料2组间比较采用χ²检验；分别采用logistic回归分析法和Cox回归分析法筛选出EVB患者治疗后再次出血的独立危险因素及5年的生存预测指标，Kaplan-Meier曲线分析累积未再出血率。结果 129例患者中有87例(67.4%)患者在随访期间发生再出血。再出血组与未再出血组患者比较，酒精性肝硬化患者比例(χ²=4.896，P=0.027)、门静脉内径(t=2.203，P=0.030)、LSM(Z=-2.771，P=0.006)和SSM(t=2.678，P=0.010)差异均有统计学意义。酒精性肝硬化患者的平均出血次数和累计出血率显著高于非酒精性肝硬化患者(P值均＜0.05)。多因素logistic回归分析显示酒精性肝硬化、LSM和SSM是EVB患者治疗后5年内再出血的独立危险因素(OR值分别为5.687、1.039、1.078，95%CI分别为1.230~26.129、1.010~1.070、1.028~1.129，P值分别为0.025、0.007、0.001)。129例患者中死亡45例(34.9%)。Cox单因素分析显示，死亡组与存活组在年龄、出血次数、平均动脉压、门静脉内径、AST、淋巴细胞百分比以及首次出血是否感染等均存在明显差异(P值均＜0.05)。进一步多因素分析表明，患者5年生存率与门静脉内径、年龄、出血次数以及首次出血时是否感染有关(OR值分别为1.459、1.053、1.286、5.239，95%CI分别为1.056~2.014、1.006~1.103、1.040~1.591、1.750~15.641，P值分别为0.022、0.026、0.020、0.003)。结论酒精性肝硬化、LSM和SSM是影响EVB患者5年内发生再出血的独立危险因素，而年龄、出血次数、门静脉内径以及首次出血时是否合并感染与5年预后有关。
- 肝硬化 /
- 食管和胃静脉曲张 /
- 出血 /
- 危险因素
Abstract: Objective To investigate the risk factors for rebleeding within 5 years and the influencing factors for 5-year survival in patients with liver cirrhosis and severe esophagogastric variceal bleeding (EVB). Methods A retrospective analysis was performed for 129 patients with liver cirrhosis who attended Tianjin Third Central Hospital from May 2012 to May 2014 due to severe EVB for the first time, with a follow-up time of 5 years. Related clinical data were analyzed, including age, sex, cause of liver cirrhosis, presence or absence of infection at the first time of bleeding, liver stiffness measurement (LSM), splenic stiffness measurement (SSM), portal vein diameter, biochemical parameters, rebleeding time, and prognosis. Esophagogastric variceal rebleeding was defined as the primary endpoint and death was defined as the secondary endpoint. The t-test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups; a logistic regression analysis was used to investigate the independent risk factors for rebleeding, and a Cox regression analysis was used to analyze the predictive indicators for 5-year survival in EVB patients; the Kaplan-Meier curve was used to analyze the cumulative non-rebleeding rate. Results Among the 129 patients, 87(67.4%) experienced rebleeding during follow-up. There were significant differences between the rebleeding group and the non-rebleeding group in the proportion of patients with alcoholic cirrhosis (χ²=4.896, P=0.027), portal vein diameter (t=2.203, P=0.030), LSM(Z=-2.771, P=0.006), and SSM(t=2.678, P=0.010). The patients with alcoholic cirrhosis had a significantly higher mean number of times of bleeding than those with non-alcoholic cirrhosis (all P < 0.05). The multivariate logistic regression analysis showed that alcoholic cirrhosis (odds ratio [OR]=5.687, 95% confidence interval [CI]: 1.230-26.129, P=0.025), LSM(OR=1.039, 95% CI: 1.010-1.070, P=0.007), and SSM(OR=1.078, 95% CI: 1.028-1.129, P=0.001) were independent risk factors for rebleeding within 5 years after treatment in EVB patients. Among the 129 patients, 45 (34.9%) died. The univariate Cox regression analysis showed that there were significant differences between the death group and the survival group in age, times of bleeding, mean arterial pressure, portal vein diameter, aspartate aminotransferase, lymphocyte percentage, and presence or absence of infection at the first time of bleeding (all P < 0.05). Further multivariate analysis showed that 5-year survival rate was associated with portal vein diameter (OR=1.459, 95% CI: 1.056-2.014, P=0.022), age (OR=1.053, 95% CI: 1.006-1.103, P=0.026), times of bleeding (OR=1.286, 95% CI: 1.040-1.591, P=0.020), and presence or absence of infection at the first time of bleeding (OR=5.239, 95% CI: 1.750-15.641, P=0.003). Conclusion Alcoholic cirrhosis, LSM, and SSM are independent risk factors for rebleeding within 5 years in EVB patients, and age, times of bleeding, portal vein diameter, and presence or absence of infection at the first time of bleeding are associated with 5-year survival.
- Liver Cirrhosis /
- Esophageal And Gastric Varices /
- Hemorrhage /
- Risk Factors

HTML全文

图 1 酒精性肝硬化患者再出血情况

下载: 全尺寸图片幻灯片

表 1 患者一般资料比较

指标	再出血组(n=87)	未再出血组(n=42)	统计值	P值	死亡组(n=45)	存活组(n=84)	统计值	P值
年龄(岁)	56.1±10.7	56.9±11.0	t=0.393	0.695	58.6±11.5	54.9±10.1	t=2.042	0.043
男性[例(%)]	60(68.9)	28(66.7)	χ²=0.069	0.793	29(64.4)	59(70.2)	χ²=0.454	0.501
肝硬化类型
乙型/丙型肝炎	45(51.7)	27(64.2)	χ²=1.812	0.178	24(53.3)	48(57.1)	χ²=0.172	0.678
酒精	23(26.4)	4(9.5)	χ²=4.896	0.027	9(20.0)	18(21.4)	χ²=0.036	0.849
其他	19(21.8)	11(26.2)	χ²=0.301	0.584	12(26.7)	18(21.4)	χ²=0.450	0.502
Child-Pugh评分(分)	7.1±1.3	7.2±1.4	t=0.542	0.588	7.4±1.5	7.0±1.2	t=1.604	0.111
Child-Pugh分级A/B(例)	37/50	16/26	χ²=0.230	0.632	14/31	39/45	χ²=2.840	0.092
感染[例(%)]	28(32.2)	13(30.9)	χ²=0.513	0.474	24(53.3)	17(20.2)	χ²=11.775	0.001
MAP(mm Hg)	86.5±10.8	87.3±10.6	t=0.355	0.723	82.4±10.2	89.2±10.4	t=3.177	0.002
WBC(×10⁹/L)	3.4(2.5~4.9)	3.4(2.3~5.9)	Z=-0.324	0.746	3.7(2.2~5.5)	3.4(2.4~4.9)	Z=-1.613	0.107
中性粒细胞百分比	67.9±10.4	71.9±10.5	t=1.830	0.070	70.4±11.5	68.6±10.1	t=0.822	0.413
淋巴细胞百分比	16.5±9.6	16.0±9.8	t=0.224	0.823	12.7±10.1	17.9±9.1	t=2.598	0.011
Hb(g/L)	96.2±30.8	102.8±23.8	t=1.195	0.234	94.4±39.2	99.9±28.3	t=0.949	0.344
PLT(×10⁹/L)	69.8±28.7	74.9±34.5	t=0.899	0.371	77.9±30.6	70.9±32.7	t=1.091	0.278
Alb(g/L)	32.2±5.7	32.8±5.5	t=0.740	0.461	33.4±6.5	33.3±5.3	t=0.080	0.937
ALT(U/L)	27(19~39.5)	23.5(16.8~47.5)	Z=-0.458	0.647	27(18.25~48.7)	24(18~37)	Z=-0.512	0.609
AST(U/L)	35(22~60)	38.5(24~65)	Z=-0.641	0.522	27.5(47~78)	22(33.5~57.8)	Z=-2.298	0.022
TBil(μmol/L)	18.4(11.7~27.9)	20.6(15.1~29.0)	Z=-1.108	0.268	16.2(11.1~27.6)	19.8(13.7~29.6)	Z=-0.074	0.941
尿素(mmol/L)	7.3±3.9	6.9±2.4	t=0.237	0.813	7.9±3.7	6.9±3.5	t=0.970	0.337
肌酐(μmol/L)	60.5±15.6	62.5±27.7	t=0.421	0.676	64.6±25.8	59.8±17.5	t=1.182	0.239
PTA	65.2±15.7	67.2±16.0	t=0.664	0.508	67.6±15.1	65.1±16.1	t=0.761	0.448
INR	1.4±0.3	1.4±0.3	t=0.456	0.649	1.4±0.3	1.4±0.3	t=0.783	0.435
门静脉内径(mm)	14.4±1.4	13.9±1.3	t=2.203	0.030	14.7±1.6	13.9±1.3	t=2.156	0.034
脾脏厚度(mm)	54.9±14.1	55.4±12.7	t=0.200	0.842	51.8±16.6	56.3±12.1	t=1.440	0.156
LSM(Kpa)	24.2(15.4~45)	19.0(13.5~24.7)	Z=-2.771	0.006	21.3(14.3~41.5)	21.3(14.3~41.5)	Z=-0.456	0.648
SSM(Kpa)	71.4±7.9	64.8±14.7	t=2.678	0.010	70.9±8.1	68.5±11.9	t=1.089	0.278
出血次数	-	-	-	-	3.4±2.7	2.4±1.6	t=2.115	0.040
死亡[例(%)]	33(37.9)	12(28.6)	χ²=1.092	0.296	-	-	-	-
套扎治疗/联合治疗(例)	13/74	5/37	χ²=0.218	0.641	7/38	11/73	χ²=0.148	0.701
注：-, 无对应数据。

下载: 导出CSV

表 2 重度食管胃底静脉曲张出血患者再出血危险因素

影响因素	B	SE	WALD	OR	95%CI	P值
酒精性肝硬化	1.738	0.778	4.992	5.687	1.230~26.129	0.025
门静脉内径	0.246	0.163	2.296	1.279	0.930~1.759	0.129
LSM	0.039	0.015	7.051	1.039	1.010~1.070	0.007
SSM	0.075	0.024	9.734	1.078	1.028~1.129	0.001

下载: 导出CSV

表 3 重度EVB患者5年预后的危险因素

影响因素	B	SE	WALD	OR	95%CI	P值
门静脉内径	0.378	0.165	5.255	1.459	1.056~2.014	0.022
年龄	0.052	0.023	4.963	1.053	1.006~1.103	0.026
出血次数	0.252	0.109	5.373	1.286	1.040~1.591	0.020
MAP	-0.019	0.022	0.740	0.981	0.939~1.025	0.390
淋巴细胞百分比	-0.028	0.023	1.480	0.972	0.929~1.017	0.224
AST	0.001	0.003	0.061	1.001	0.996~1.006	0.805
首次出血合并感染	1.656	0.558	8.806	5.239	1.750~15.641	0.003

下载: 导出CSV

参考文献(23)

[1]	GARCIA-TSAO G, ABRALDES JG, BERZIGOTTI A, et al. Portal hypertensive bleeding in cirrhosis: Risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases[J]. Hepatology, 2017, 65(1): 310-335. DOI: 10.1002/hep.28906.
[2]	Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Gastroenterology, Chinese Medical Association; Chinese Society of Endoscopy, Chinese Medical Association. Guidelines for the diagnosis and treatment of esophageal and gastric variceal bleeding in cirrhotic portal hypertension[J]. J Clin Hepatol, 2016, 32(2): 203-219. DOI: 10.3969/j.issn.1001-5256.2016.02.002. 中华医学会肝病学分会, 中华医学会消化病学分会, 中华医学会内镜学分会. 肝硬化门静脉高压食管胃静脉曲张出血的防治指南[J]. 临床肝胆病杂志, 2016, 32(2): 203-219. DOI: 10.3969/j.issn.1001-5256.2016.02.002.
[3]	BOSCH J, GARCíA-PAGÁN JC. Prevention of variceal rebleeding[J]. Lancet, 361(9361): 952-954. DOI: 10.1016/S0140-6736(03)12778-X.
[4]	de FRANCHIS R, BAVENO VI Faculty. Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension[J]. J Hepatol, 2015, 63(3): 743-752. DOI: 10.1016/j.jhep.2015.05.022.
[5]	Chinese Society of Hepatology, Chinese Medical Association. Chinese guidelines on the management of liver cirrhosis[J]. J Clin Hepatol, 2019, 35(11): 2408-2425. DOI: 10.3969/j.issn.1001-5256.2019.11.006. 中华医学会肝病学分会. 肝硬化诊治指南[J]. 临床肝胆病杂志, 2019, 35(11): 2408-2425. DOI: 10.3969/j.issn.1001-5256.2019.11.006.
[6]	Committee of Esophageal Varicosity, Society of Digestive Endoscopy Chinese Medical Association. Tentative guidelines endoscopic diagnosis and treatment of varicosity and variceal bleeding in digestive tract (2009)[J]. Chin J Dig Endosc, 2010, 27(1): 1-4. DOI: 10.3760/cma.j.issn.1007-5232.2010.01.001. 中华医学会消化内镜学分会食管胃静脉曲张学组. 消化道静脉曲张及出血的内镜诊断和治疗规范试行方案(2009年)[J]. 中华消化内镜杂志, 2010, 27(1): 1-4. DOI: 10.3760/cma.j.issn.1007-5232.2010.01.001.
[7]	SHARMA P, SARIN SK. Improved survival with the patients with variceal bleed[J]. Int J Hepatol, 2011, 2011: 356919. DOI: 10.4061/2011/356919.
[8]	Chinese Portal Hypertension Diagnosis and Monitoring Study Group(CHESS); Minimally Invasive Intervention Collaborative Group, Chinese Society of Gastroenterology; Emergency Intervention Committee, Chinese College of Interventionalists, et al. Consensus on clinical application of hepatic venous pressure gradient in China (2018)[J]. J Clin Hepatol, 2018, 34(12): 2526-2536. DOI: 10.3969/j.issn.1001-5256.2018.12.008 中国门静脉高压诊断与监测研究组(CHESS), 中华医学会消化病学分会微创介入协作组, 中国医师协会介入医师分会急诊介入专业委员会, 等. 中国肝静脉压力梯度临床应用专家共识(2018版)[J]. 临床肝胆病杂志, 2018, 34(12): 2526-2536. DOI: 10.3969/j.issn.1001-5256.2018.12.008
[9]	ABD EL RIHIM AY, OMAR RF, FATHALAH W, et al. Role of fibroscan and APRI in detection of liver fibrosis: A systematic review and meta-analysis[J]. Arab J Gastroenterol, 2013, 14(2): 44-50. DOI: 10.1016/j.ajg.2013.05.002.
[10]	BUREAU C, METIVIER S, PERON JM, et al. Transient elastography accurately predicts presence of significant portal hypertension in patients with chronic liver disease[J]. Aliment Pharmacol Ther, 2008, 27(12): 1261-1268. DOI: 10.1111/j.1365-2036.2008.03701.x.
[11]	LIU F, LI TH, HAN T, et al. Non-invasive assessment of portal hypertension in patients with liver cirrhosis using FibroScan transient elastography[J]. Chin J Hepatol, 2013, 21(11): 840- 844. DOI: 10.3760/cma.j.issn.1007-3418.2013.11.010. 刘芳, 李庭红, 韩涛, 等. 瞬时弹性成像在肝硬化门静脉高压中的临床评价[J]. 中华肝脏病杂志, 2013, 21(11): 840-844. DOI: 10.3760/cma.j.issn.1007-3418.2013.11.010.
[12]	LI TH, LIU F, HAN T, et al. Noninvasive assessment of esophageal-gastric varices by spleen stiffiness liver cirrhosis patients[J]. Chin J Infect, 2012, 30(10): 603-608. DOI: 10.3760/cma.j.issn.1000-6680.2012.10.006. 李庭红, 刘芳, 韩涛, 等. 脾脏硬度对肝硬化患者食管胃底静脉曲张的评估[J]. 中华传染病杂志, 2012, 30(10): 603-608. DOI: 10.3760/cma.j.issn.1000-6680.2012.10.006.
[13]	COLECCHIA A, MONTRONE L, SCAIOLI E, et al. Measurement of spleen stiffness to evaluate portal hypertension and the presence of esophageal varices in patients with HCV-related cirrhosis[J]. Gastroenterology, 2012, 143(3): 646-654. DOI: 10.1053/j.gastro.2012.05.035.
[14]	TAKUMA Y, NOUSO K, MORIMOTO Y, et al. Portal hypertension in patients with liver cirrhosis: Diagnostic accuracy of spleen stiffness[J]. Radiology, 2016, 279(2): 609-619. DOI: 10.1148/radiol.2015150690.
[15]	SHARMA P, KIRNAKE V, TYAGI P, et al. Spleen stiffness in patients with cirrhosis in predicting esophageal varices[J]. Am J Gastroenterol, 2013, 108(7): 1101-1107. DOI: 10.1038/ajg.2013.119.
[16]	NILLES KM, FLAMM SL. Thrombocytopenia in chronic liver disease: New management strategies[J]. Clin Liver Dis, 2020, 24(3): 437-451. DOI: 10.1016/j.cld.2020.04.009.
[17]	MEJIAS M, GARCIA-PRAS E, GALLEGO J, et al. Relevance of the mTOR signaling pathway in the pathophysiology of splenomegaly in rats with chronic portal hypertension[J]. J Hepatol, 2010, 52(4): 529-539. DOI: 10.1016/j.jhep.2010.01.004.
[18]	LAMEIRÄO GOMES C, VIOLANTE SILVA R, CARROLA P, et al. Bacterial infections in patients with liver cirrhosis in an internal medicine department[J]. GE Port J Gastroenterol, 2019, 26(5): 324-332. DOI: 10.1159/000494568.
[19]	GELETO G, GETNET W, TEWELDE T. Mean normal portal vein diameter using sonography among clients coming to radiology department of Jimma university hospital, Southwest Ethiopia[J]. Ethiop J Health Sci, 2016, 26(3): 237-242. DOI: 10.4314/ejhs.v26i3.6.
[20]	TANEJA SK, DHIMAN RK. Prevention and management of bacterial infections in cirrhosis[J]. Int J Hepatol, 2011, 2011: 784540. DOI: 10.4061/2011/784540.
[21]	Ali A, Swingland J, Choi CH, et al. OC-143 Artificial neural network for the risk stratification of acute upper gastrointestinal bleeding: multicentre comparative analysis vs the Glasgow Blatchford and rockall scores[J]. Gut, 2012, 61(Suppl 2): A62. DOI: 10.1136/gutjnl-2012-302514a.143.
[22]	FERNANDEZ J, ARROYO V. Bacterial infections in cirrhosis: A growing problem with significant implications[J]. Clin Liver Dis (Hoboken), 2013, 2(3): 102-105. DOI: 10.1002/cld.169.
[23]	PARK EJ, JANG JY, LEE JE, et al. The risk factors for bleeding of fundal varices in patients with liver cirrhosis[J]. Gut Liver, 2013, 7(6): 704-711. DOI: 10.5009/gnl.2013.7.6.704.