肝硬化并发门静脉血栓的危险因素与防护策略

冯文娟; 周宁; 汪雨露; 白兆琴

doi:10.12449/JCH240128

肝硬化并发门静脉血栓的危险因素与防护策略

DOI: 10.12449/JCH240128

冯文娟¹,
周宁^{1, 2, , ,},
汪雨露¹,
白兆琴^{1, 2}

1.
甘肃中医药大学，兰州 730000
2.
兰州市第一人民医院消化科，兰州 730050

基金项目:

甘肃省科技厅重点研发项目 (21YF5FA169);

兰州市人才创新创业项目 (2021-RC-107)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：冯文娟负责文献检索、文章构思并撰写论文；周宁负责指导论文撰写与修改；汪雨露、白兆琴参与文献检索和文献分析。

详细信息

通信作者:
周宁， zhouning198278@163.com （ORCID： 0000-0001-8988-2860）

计量
- 文章访问数: 394
- HTML全文浏览量: 102
- PDF下载量: 65
- 被引次数: 0
出版历程
- 收稿日期: 2023-04-27
- 录用日期: 2023-05-23
- 出版日期: 2024-01-23

Portal vein thrombosis in liver cirrhosis： Risk factors and protection strategies

Wenjuan FENG¹,
Ning ZHOU^{1, 2
, ,
,},
Yulu WANG¹,
Zhaoqin BAI^{1, 2}

1.
Gansu University of Chinese Medicine，Lanzhou 730000，China
2.
Department of Gastroenterology，Lanzhou First People’s Hospital，Lanzhou 730050，China

Research funding:

Key Research and Development Project of Science and Technology Department of Gansu Province (21YF5FA169);

Lanzhou Talent Innovation and Entrepreneurship Project (2021-RC-107)

More Information

Corresponding author: ZHOU Ning， zhouning198278@163.com （ORCID： 0000-0001-8988-2860）

摘要

摘要: 门静脉血栓（PVT）形成是肝硬化自然病程中的常见并发症之一，对肝硬化进展有重要影响。本文着重总结了PVT发生的危险因素、预后等方面的研究进展。PVT形成的危险因素较多，Virchow三要素即门静脉血流阻滞、血液高凝状态、手术或创伤引起的血管内皮损伤以及全身炎症等被认为是PVT发生发展的主要原因。目前具有临床应用前景的PVT发生风险预测模型尚需更多前瞻性研究验证。肝硬化PVT患者的预后较差，完全闭塞性PVT与肝移植术后病死率升高相关。肝硬化患者预防性抗凝治疗已被证实安全有效，将有助于PVT的防治管理。
- 肝硬化 /
- 门静脉 /
- 静脉血栓形成
Abstract: Portal vein thrombosis （PVT） is one of the common complications during the natural course of liver cirrhosis and has an important influence on the progression of liver cirrhosis. This article mainly summarizes the research advances in the risk factors for PVT. There are many risk factors for PVT， and Virchow’s triad， namely venous stasis， hypercoagulability， and vascular endothelial injury and systemic inflammation caused by surgery or trauma， are considered the main reasons for the development and progression of PVT. At present， more prospective studies are still needed to validate the predictive models for the risk of PVT that have certain application prospects in clinical practice. Cirrhotic patients with PVT tend to have a poor prognosis， and complete obstructive PVT is associated with increased mortality after liver transplantation. Recent studies have shown that prophylactic anticoagulant therapy is safe and effective in patients with liver cirrhosis and can thus help with the prevention and treatment of PVT.
- Liver Cirrhosis /
- Portal Vein /
- Venous Thrombosis

HTML全文

参考文献(59)

[1]	HAN GH, QI XS, HE CY, et al. Transjugular intrahepatic portosystemic shunt for portal vein thrombosis with symptomatic portal hypertension in liver cirrhosis[J]. J Hepatol, 2011, 54( 1): 78- 88. DOI: 10.1016/j.jhep.2010.06.029.
[2]	BALFOUR GW, STEWART TG. Case of enlarged spleen complicated with ascites, both depending upon varicose dilatation and thrombosis of the portal vein[J]. Edinb Med J, 1869, 14( 7): 589- 598.
[3]	FACCIA M, AINORA ME, PONZIANI FR, et al. Portal vein thrombosis in cirrhosis: Why a well-known complication is still matter of debate[J]. World J Gastroenterol, 2019, 25( 31): 4437- 4451. DOI: 10.3748/wjg.v25.i31.4437.
[4]	NORONHA FERREIRA C, MARINHO RT, CORTEZ-PINTO H, et al. Incidence, predictive factors and clinical significance of development of portal vein thrombosis in cirrhosis: A prospective study[J]. Liver Int, 2019, 39( 8): 1459- 1467. DOI: 10.1111/liv.14121.
[5]	PAN JH, WANG L, GAO FB, et al. Epidemiology of portal vein thrombosis in liver cirrhosis: A systematic review and meta-analysis[J]. Eur J Intern Med, 2022, 104: 21- 32. DOI: 10.1016/j.ejim.2022.05.032.
[6]	NERY F, CHEVRET S, CONDAT B, et al. Causes and consequences of portal vein thrombosis in 1, 243 patients with cirrhosis: Results of a longitudinal study[J]. Hepatology, 2015, 61( 2): 660- 667. DOI: 10.1002/hep.27546.
[7]	NORTHUP PG, GARCIA-PAGAN JC, GARCIA-TSAO G, et al. Vascular liver disorders, portal vein thrombosis, and procedural bleeding in patients with liver disease: 2020 practice guidance by the American association for the study of liver diseases[J]. Hepatology, 2021, 73( 1): 366- 413. DOI: 10.1002/hep.31646.
[8]	Hepatobiliary Disease Study Group, Chinese Society of Gastroenterology, Chinese Medical Association. Consensus for management of portal vein thrombosis in liver cirrhosis(2020, Shanghai)[J]. J Clin Hepatol, 2020, 36( 12): 2667- 2674. DOI: 10.3969/j.issn.1001-5256.2020.12.007. 中华医学会消化病学分会肝胆疾病学组. 肝硬化门静脉血栓管理专家共识(2020年,上海)[J]. 临床肝胆病杂志, 2020, 36( 12): 2667- 2674. DOI: 10.3969/j.issn.1001-5256.2020.12.007.
[9]	ODRIOZOLA A, PUENTE Á, CUADRADO A, et al. Portal vein thrombosis in the setting of cirrhosis: A comprehensive review[J]. J Clin Med, 2022, 11( 21): 6435. DOI: 10.3390/jcm11216435.
[10]	YERDEL MA, GUNSON B, MIRZA D, et al. Portal vein thrombosis in adults undergoing liver transplantation: Risk factors, screening, management, and outcome[J]. Transplantation, 2000, 69( 9): 1873- 1881. DOI: 10.1097/00007890-200005150-00023.
[11]	ANTON A, CAMPRECIÓS G, PÉREZ-CAMPUZANO V, et al. The pathophysiology of portal vein thrombosis in cirrhosis: Getting deeper into virchow’s triad[J]. J Clin Med, 2022, 11( 3): 800. DOI: 10.3390/jcm11030800.
[12]	BIOLATO M, PARATORE M, di GIALLEONARDO L, et al. Direct oral anticoagulant administration in cirrhotic patients with portal vein thrombosis: What is the evidence?[J]. World J Hepatol, 2022, 14( 4): 682- 695. DOI: 10.4254/wjh.v14.i4.682.
[13]	NERY F, CORREIA S, MACEDO C, et al. Nonselective beta-blockers and the risk of portal vein thrombosis in patients with cirrhosis: Results of a prospective longitudinal study[J]. Aliment Pharmacol Ther, 2019, 49( 5): 582- 588. DOI: 10.1111/apt.15137.
[14]	XU XB, GUO XZ, de STEFANO V, et al. Nonselective beta-blockers and development of portal vein thrombosis in liver cirrhosis: A systematic review and meta-analysis[J]. Hepatol Int, 2019, 13( 4): 468- 481. DOI: 10.1007/s12072-019-09951-6.
[15]	TURON F, DRIEVER EG, BAIGES A, et al. Predicting portal thrombosis in cirrhosis: A prospective study of clinical, ultrasonographic and hemostatic factors[J]. J Hepatol, 2021, 75( 6): 1367- 1376. DOI: 10.1016/j.jhep.2021.07.020.
[16]	PRAKTIKNJO M, TREBICKA J, CARNEVALE R, et al. Von willebrand and factor VIII portosystemic circulation gradient in cirrhosis: Implications for portal vein thrombosis[J]. Clin Transl Gastroenterol, 2020, 11( 2): e00123. DOI: 10.14309/ctg.0000000000000123.
[17]	HUNG HC, LEE JC, CHENG CH, et al. Protein S for portal vein thrombosis in cirrhotic patients waiting for liver transplantation[J]. J Clin Med, 2020, 9( 4): 1181. DOI: 10.3390/jcm9041181.
[18]	SCHEINER B, BALCAR L, NUSSBAUMER RJ, et al. Factor VIII/protein C ratio independently predicts liver-related events but does not indicate a hypercoagulable state in ACLD[J]. J Hepatol, 2022, 76( 5): 1090- 1099. DOI: 10.1016/j.jhep.2021.12.038.
[19]	LA MURA V, TRIPODI A, TOSETTI G, et al. Resistance to thrombomodulin is associated with de novo portal vein thrombosis and low survival in patients with cirrhosis[J]. Liver Int, 2016, 36( 9): 1322- 1330. DOI: 10.1111/liv.13087.
[20]	QUECK A, CARNEVALE R, USCHNER FE, et al. Role of portal venous platelet activation in patients with decompensated cirrhosis and TIPS[J]. Gut, 2020, 69( 8): 1535- 1536. DOI: 10.1136/gutjnl-2019-319044.
[21]	CARNEVALE R, RAPARELLI V, NOCELLA C, et al. Gut-derived endotoxin stimulates factor VIII secretion from endothelial cells. Implications for hypercoagulability in cirrhosis[J]. J Hepatol, 2017, 67( 5): 950- 956. DOI: 10.1016/j.jhep.2017.07.002.
[22]	MA SD, WANG J, BEZINOVER D, et al. Inherited thrombophilia and portal vein thrombosis in cirrhosis: A systematic review and meta-analysis[J]. Res Pract Thromb Haemost, 2019, 3( 4): 658- 667. DOI: 10.1002/rth2.12253.
[23]	LIU RH, LIAN HL. Early predictive value of P-selectin and D-dimer for portal vein thrombosis in patients with liver cirrhosis[J]. Chin J Thromb Hemostasis, 2021, 27( 6): 974- 976. DOI: 10.3969/j.issn.1009-6213.2021.06.031 刘瑞红, 廉恒丽. P-选择素和D二聚体对肝硬化门静脉血栓形成的早期预测价值[J]. 血栓与止血学, 2021, 27( 6): 974- 976. DOI: 10.3969/j.issn.1009-6213.2021.06.031
[24]	REN WH, ZHANG J, CHEN YY, et al. Evaluation of coagulation, fibrinolysis and endothelial biomarkers in cirrhotic patients with or without portal venous thrombosis[J]. Clin Appl Thromb Hemost, 2020, 26: 1076029620982666. DOI: 10.1177/1076029620982666.
[25]	SHALABY S, SIMIONI P, CAMPELLO E, et al. Endothelial damage of the portal vein is associated with heparin-like effect in advanced stages of cirrhosis[J]. Thromb Haemost, 2020, 120( 8): 1173- 1181. DOI: 10.1055/s-0040-1713169.
[26]	SWINSON B, WATERS PS, WEBBER L, et al. Portal vein thrombosis following elective laparoscopic splenectomy: Incidence and analysis of risk factors[J]. Surg Endosc, 2022, 36( 5): 3332- 3339. DOI: 10.1007/s00464-021-08649-x.
[27]	QI XS, HAN GH, YE C, et al. Splenectomy causes 10-fold increased risk of portal venous system thrombosis in liver cirrhosis patients[J]. Med Sci Monit, 2016, 22: 2528- 2550. DOI: 10.12659/msm.898866.
[28]	DING JN, ZHAO WF. Analysis on risk factors and clinical features of portal vein thrombosis of patients with cirrhosis[J/CD]. Chin J Liver Dis Electron Version, 2022, 14( 4): 48- 54. DOI: 10.3969/j.issn.1674-7380.2022.04.008. 丁靖诺, 赵卫峰. 肝硬化门静脉血栓形成危险因素及临床特征分析[J/CD]. 中国肝脏病杂志(电子版), 2022, 14( 4): 48- 54. DOI: 10.3969/j.issn.1674-7380.2022.04.008.
[29]	JIANG GQ, BAI DS, CHEN P, et al. Risk factors for portal vein system thrombosis after laparoscopic splenectomy in cirrhotic patients with hypersplenism[J]. J Laparoendosc Adv Surg Tech A, 2016, 26( 6): 419- 423. DOI: 10.1089/lap.2015.0481.
[30]	HUANG L, YU QS, PENG H. Hemorheological alteration in patients with cirrhosis clinically diagnosed with portal vein system thrombosis after splenectomy[J]. Med Sci Monit, 2021, 27: e931157. DOI: 10.12659/MSM.931157.
[31]	OGAWA S, YAMAMOTO A, JOGO A, et al. Splenic vein diameter is a risk factor for the portal venous system thrombosis after partial splenic artery embolization[J]. Cardiovasc Intervent Radiol, 2021, 44( 6): 921- 930. DOI: 10.1007/s00270-020-02751-8.
[32]	HAN JB, SHU QH, ZHANG YF, et al. Predictive value of inflammation biomarkers in patients with portal vein thrombosis[J]. J Clin Transl Hepatol, 2021, 9( 3): 384- 391. DOI: 10.14218/JCTH.2020.00159.
[33]	XING YY, JIANG YP, XING SC, et al. Neutrophil extracellular traps are associated with enhanced procoagulant activity in liver cirrhosis patients with portal vein thrombosis[J]. J Clin Lab Anal, 2022, 36( 5): e24433. DOI: 10.1002/jcla.24433.
[34]	XING YY, TIAN ZB, JIANG YP, et al. A practical nomogram based on systemic inflammatory markers for predicting portal vein thrombosis in patients with liver cirrhosis[J]. Ann Med, 2022, 54( 1): 302- 309. DOI: 10.1080/07853890.2022.2028893.
[35]	HUANG XQ, FAN XW, ZHANG R, et al. Systemic inflammation and portal vein thrombosis in cirrhotic patients with gastroesophageal varices[J]. Eur J Gastroenterol Hepatol, 2020, 32( 3): 401- 405. DOI: 10.1097/MEG.0000000000001526.
[36]	NERY F, CARNEIRO P, CORREIA S, et al. Systemic inflammation as a risk factor for portal vein thrombosis in cirrhosis: A prospective longitudinal study[J]. Eur J Gastroenterol Hepatol, 2021, 33( Suppl 1): e108- e113. DOI: 10.1097/MEG.0000000000001982.
[37]	AK C, ADALI G, SAYAR S, et al. Portal vein thrombosis risk factors in liver transplant candidates[J]. Hepatol Forum, 2022, 3( 3): 88- 92. DOI: 10.14744/hf.2022.2022.0005.
[38]	FACCIA M, SANTOPAOLO F, GASBARRINI A, et al. Risk factors for portal vein thrombosis or venous thromboembolism in a large cohort of hospitalized cirrhotic patients[J]. Intern Emerg Med, 2022, 17( 5): 1327- 1334. DOI: 10.1007/s11739-022-02928-8.
[39]	SARIN SK, PHILIPS CA, KAMATH PS, et al. Toward a comprehensive new classification of portal vein thrombosis in patients with cirrhosis[J]. Gastroenterology, 2016, 151( 4): 574- 577. e 3. DOI: 10.1053/j.gastro.2016.08.033.
[40]	GABALLA D, BEZINOVER D, KADRY Z, et al. Development of a model to predict portal vein thrombosis in liver transplant candidates: The portal vein thrombosis risk index[J]. Liver Transpl, 2019, 25( 12): 1747- 1755. DOI: 10.1002/lt.25630.
[41]	LI J, WU QQ, ZHU RH, et al. Machine learning predicts portal vein thrombosis after splenectomy in patients with portal hypertension: Comparative analysis of three practical models[J]. World J Gastroenterol, 2022, 28( 32): 4681- 4697. DOI: 10.3748/wjg.v28.i32.4681.
[42]	ZANETTO A, RODRIGUEZ-KASTRO KI, GERMANI G, et al. Mortality in liver transplant recipients with portal vein thrombosis-an updated meta-analysis[J]. Transpl Int, 2018, 31( 12): 1318- 1329. DOI: 10.1111/tri.13353.
[43]	WEI TT, LIANG BL, LIU HM, et al. Nomogram on predicting the prognosis of hepatocellular carcinoma with portal vein tumor thrombus[J/CD]. Chin J Liver Dis Electron Version, 2022, 14( 3): 28- 38. DOI: 10.3969/j.issn.1674-7380.2022.03.007. 魏天桐, 梁保丽, 刘慧敏, 等. 列线图预测肝细胞癌合并门静脉癌栓预后[J/CD]. 中国肝脏病杂志(电子版), 2022, 14( 3): 28- 38. DOI: 10.3969/j.issn.1674-7380.2022.03.007.
[44]	QI XS, GUO XZ, YOSHIDA EM, et al. Transient portal vein thrombosis in liver cirrhosis[J]. BMC Med, 2018, 16( 1): 83. DOI: 10.1186/s12916-018-1069-8.
[45]	WANG L, XU XB, HOU Y, et al. Acute mesenteric vein thrombosis after endoscopic injection sclerotherapy for esophageal varices in a patient with liver cirrhosis[J]. Drug Discov Ther, 2019, 13( 2): 118- 121. DOI: 10.5582/DDT.2019.01014.
[46]	COOL J, ROSENBLATT R, KUMAR S, et al. Portal vein thrombosis prevalence and associated mortality in cirrhosis in a nationally representative inpatient cohort[J]. J Gastroenterol Hepatol, 2019, 34( 6): 1088- 1092. DOI: 10.1111/jgh.14501.
[47]	XIAO CT, LI XQ, GAN PL, et al. Influence of portal vein thrombosis on the prognosis of patients with liver cirrhosis based on propensity score matching[J]. J Clin Hepatol, 2021, 37( 8): 1829- 1835. DOI: 10.3969/j.issn.1001-5256.2021.08.017. 肖春桃, 李贤秋, 甘佩灵, 等. 基于倾向性评分匹配分析门静脉血栓对肝硬化患者预后的影响[J]. 临床肝胆病杂志, 2021, 37( 8): 1829- 1835. DOI: 10.3969/j.issn.1001-5256.2021.08.017.
[48]	HE QL, YU BP, XIAO Y. Risk factors of rebleeding in cirrhotic patients with esophageal gastric variceal bleeding after endoscopic treatment[J]. Chin Hepatol, 2023, 28( 1): 55- 60. DOI: 10.14000/j.cnki.issn.1008-1704.2023.01.022. 何青莲, 余保平, 肖勇. 肝硬化食管胃静脉曲张出血患者内镜治疗后再出血的危险因素分析[J]. 肝脏, 2023, 28( 1): 55- 60. DOI: 10.14000/j.cnki.issn.1008-1704.2023.01.022.
[49]	ZHAI W, CHEN YZ, TONG YL. Comparison of curative effect of esophageal variceal ligation in patients with or without portal vein thrombosis[J]. Henan Med Res, 2020, 29( 36): 6736- 6739. DOI: 10.3969/j.issn.1004-437X.2020.36.005. 翟威, 陈永忠, 仝亚林. 有无门静脉血栓患者食管静脉曲张套扎术的疗效差异分析[J]. 河南医学研究, 2020, 29( 36): 6736- 6739. DOI: 10.3969/j.issn.1004-437X.2020.36.005.
[50]	NACIF LS, ZANINI LY, PINHEIRO RS, et al. Portal vein surgical treatment on non-tumoral portal vein thrombosis in liver transplantation: Systematic Review and Meta-Analysis[J]. Clinics, 2021, 76: e2184. DOI: 10.6061/clinics/2021/e2184.
[51]	CHEN ZJ, RAN T, CAO HY, et al. The impact of portal vein thrombosis on the prognosis of patients with cirrhosis: A retrospective propensity-score matched study[J]. Front Med, 2021, 8: 685944. DOI: 10.3389/fmed.2021.685944.
[52]	XIAN JC, TANG YZ, SHAO H, et al. Effect of portal vein thrombosis on the prognosis of patients with cirrhosis without a liver transplant: A systematic review and meta-analysis[J]. Medicine, 2021, 100( 16): e25439. DOI: 10.1097/MD.0000000000025439.
[53]	ZHANG ZQ, ZHAO Y, LI DD, et al. Safety, efficacy and prognosis of anticoagulant therapy for portal vein thrombosis in cirrhosis: A retrospective cohort study[J]. Thromb J, 2023, 21( 1): 13. DOI: 10.1186/s12959-023-00454-x.
[54]	HAN JM, KOH Y, KIM SH, et al. Evaluation of low-molecular-weight heparin for treatment of portal vein thrombosis in liver cirrhosis patients[J]. Medicina, 2023, 59( 2): 292. DOI: 10.3390/medicina59020292.
[55]	LI YN, FU XQ, LI Y, et al. Early prevention and risk factors analysis of portal vein system thrombosis after laparoscopic splenectomy and pericardial devascularization[J]. Surg Endosc, 2022, 36( 12): 8918- 8926. DOI: 10.1007/s00464-022-09340-5.
[56]	LI Y, GAO L, HU YX, et al. Application of low molecular weight heparin calcium combined with dextran in prevention of venous thrombosis after liver cirrhosis and portal hypertension surgery[J]. Chin Hepatol, 2019, 24( 7): 788- 790. DOI: 10.14000/j.cnki.issn.1008-1704.2019.07.021. 李英, 高磊, 胡扬喜, 等. 低分子肝素钙联合右旋糖酐在肝硬化门静脉高压症术后静脉血栓形成预防中的应用[J]. 肝脏, 2019, 24( 7): 788- 790. DOI: 10.14000/j.cnki.issn.1008-1704.2019.07.021.
[57]	NG CH, TAN DJH, NISTALA KRY, et al. A network meta-analysis of direct oral anticoagulants for portal vein thrombosis in cirrhosis[J]. Hepatol Int, 2021, 15( 5): 1196- 1206. DOI: 10.1007/s12072-021-10247-x.
[58]	LIU L, LI JY, LIU CY, et al. Effect of Ganshuang Granule combined with entecavir on portal vein thrombosis in patients with hepatitis B cirrhosis[J]. J Clin Hepatol, 2022, 38( 9): 2020- 2026. DOI: 10.3969/j.issn.1001-5256.2022.09.015. 刘立, 李俊义, 刘春云, 等. 肝爽颗粒联合恩替卡韦对乙型肝炎肝硬化患者门静脉血栓发生的影响[J]. 临床肝胆病杂志, 2022, 38( 9): 2020- 2026. DOI: 10.3969/j.issn.1001-5256.2022.09.015.
[59]	DRIEVER EG, von MEIJENFELDT FA, ADELMEIJER J, et al. Nonmalignant portal vein thrombi in patients with cirrhosis consist of intimal fibrosis with or without a fibrin-rich thrombus[J]. Hepatology, 2022, 75( 4): 898- 911. DOI: 10.1002/hep.32169.