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DOI: 10.1055/s-0040-1715473
New Insights into the Pathogenesis, Risk Factors, and Treatment of Portal Vein Thrombosis in Patients with Cirrhosis
Funding J.C.G.P. received support in part through grants from the Spanish Ministry of Education and Science (SAF-2016–75767-R), Fondo Europeo de Desarrollo Regional (FEDER) (PIE15/00027), “Commissioner for Universities and Research of the Generalitat de Catalunya” (AGAUR SGR 2017), and The Spanish Health Ministry (National Strategic Plan against Hepatitis C) Secretariat for Universities and Research of the Department of Economy and Knowledge (SGR17_00517). V.H-G. received support from the Spanish Ministry of Education and Science (PI17/00398) and the Spanish Health Ministry (National Strategic Plan against Hepatitis C). A.B and M.M. are recipients of a “Río Hortega” fellowship grant from the Instituto de Salud Carlos III.![](https://www.thieme-connect.de/media/sth/202006/lookinside/thumbnails/10-1055-s-0040-1715473_02778-1.jpg)
Abstract
Portal vein thrombosis (PVT) is a frequent event in patients with cirrhosis regardless of etiology. Notwithstanding the commonality of the problem, the pathophysiology and risk factors for PVT in cirrhosis are largely unknown. The clinical impact of PVT in the natural history of cirrhosis is unclear, indications for PVT treatment are not well defined, and treatment recommendations are based on experts' opinion and consensus only. Therefore, this review aims to summarize current knowledge of mechanisms and risk factors for PVT development and assess the current evidence of PVT management, with a special focus on strategies of anticoagulation and transjugular intrahepatic portosystemic shunt placement.
Publication History
Article published online:
20 August 2020
© 2020. Thieme. All rights reserved.
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References
- 1 Mantaka A, Augoustaki A, Kouroumalis EA, Samonakis DN. Portal vein thrombosis in cirrhosis: diagnosis, natural history, and therapeutic challenges. Ann Gastroenterol 2018; 31 (03) 315-329
- 2 Francoz C, Belghiti J, Vilgrain V. , et al. Splanchnic vein thrombosis in candidates for liver transplantation: usefulness of screening and anticoagulation. Gut 2005; 54 (05) 691-697
- 3 Eshraghian A, Nikeghbalian S, Kazemi K. , et al. Portal vein thrombosis in patients with liver cirrhosis and its impact on early and long-term outcomes after liver transplantation. Int J Clin Pract 2018; 73: e13309
- 4 Qi X, De Stefano V, Li H, Dai J, Guo X, Fan D. Anticoagulation for the treatment of portal vein thrombosis in liver cirrhosis: a systematic review and meta-analysis of observational studies. Eur J Intern Med 2015; 26 (01) 23-29
- 5 Maruyama H, Okugawa H, Takahashi M, Yokosuka O. De novo portal vein thrombosis in virus-related cirrhosis: predictive factors and long-term outcomes. Am J Gastroenterol 2013; 108 (04) 568-574
- 6 Nery F, Chevret S, Condat B. , et al; Groupe d'Etude et de Traitement du Carcinome Hépatocellulaire. Causes and consequences of portal vein thrombosis in 1,243 patients with cirrhosis: results of a longitudinal study. Hepatology 2015; 61 (02) 660-667
- 7 Noronha Ferreira C, Reis D, Cortez-Pinto H. , et al. Anticoagulation in cirrhosis and portal vein thrombosis is safe and improves prognosis in advanced cirrhosis. Dig Dis Sci 2019; 64 (09) 2671-2683
- 8 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. Liver Int 2019; 39 (08) 1459-1467
- 9 Amitrano L, Guardascione MA, Brancaccio V. , et al. Risk factors and clinical presentation of portal vein thrombosis in patients with liver cirrhosis. J Hepatol 2004; 40 (05) 736-741
- 10 Zocco MA, Di Stasio E, De Cristofaro R. , et al. Thrombotic risk factors in patients with liver cirrhosis: correlation with MELD scoring system and portal vein thrombosis development. J Hepatol 2009; 51 (04) 682-689
- 11 Stine JG, Wang J, Shah PM. , et al. Decreased portal vein velocity is predictive of the development of portal vein thrombosis: a matched case-control study. Liver Int 2018; 38 (01) 94-101
- 12 Abdel-Razik A, Mousa N, Elhelaly R, Tawfik A. De-novo portal vein thrombosis in liver cirrhosis: risk factors and correlation with the Model for End-stage Liver Disease scoring system. Eur J Gastroenterol Hepatol 2015; 27 (05) 585-592
- 13 Leonardi F, Maria N, Villa E. Anticoagulation in cirrhosis: a new paradigm?. Clin Mol Hepatol 2017; 23 (01) 13-21
- 14 Lisman T, Porte RJ. Rebalanced hemostasis in patients with liver disease: evidence and clinical consequences. Blood 2010; 116 (06) 878-885
- 15 O'Leary JG, Greenberg CS, Patton HM, Caldwell SH. AGA Clinical Practice Update: coagulation in cirrhosis. Gastroenterology 2019; 157 (01) 34-43.e1
- 16 Tripodi A, Mannucci PM. The coagulopathy of chronic liver disease. N Engl J Med 2011; 365 (02) 147-156
- 17 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. Liver Int 2016; 36 (09) 1322-1330
- 18 Intagliata NM, Caldwell SH, Tripodi A. Diagnosis, development, and treatment of portal vein thrombosis in patients with and without cirrhosis. Gastroenterology 2019; 156 (06) 1582-1599.e1
- 19 Carnevale R, Raparelli V, Nocella C. , et al. Gut-derived endotoxin stimulates factor VIII secretion from endothelial cells. Implications for hypercoagulability in cirrhosis. J Hepatol 2017; 67 (05) 950-956
- 20 Raparelli V, Basili S, Carnevale R. , et al. Low-grade endotoxemia and platelet activation in cirrhosis. Hepatology 2017; 65 (02) 571-581
- 21 Mackman N. New insights into the mechanisms of venous thrombosis. J Clin Invest 2012; 122 (07) 2331-2336
- 22 de Franchis R. Baveno V Faculty. Revising consensus in portal hypertension: report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol 2010; 53 (04) 762-768
- 23 Xu X, Guo X, De Stefano V. , et al. Nonselective beta-blockers and development of portal vein thrombosis in liver cirrhosis: a systematic review and meta-analysis. Hepatol Int 2019; 13 (04) 468-481
- 24 Amitrano L, Brancaccio V, Guardascione MA. , et al. Inherited coagulation disorders in cirrhotic patients with portal vein thrombosis. Hepatology 2000; 31 (02) 345-348
- 25 Saugel B, Lee M, Feichtinger S, Hapfelmeier A, Schmid RM, Siveke JT. Thrombophilic factor analysis in cirrhotic patients with portal vein thrombosis. J Thromb Thrombolysis 2015; 40 (01) 54-60
- 26 Ma SD, Wang J, Bezinover D, Kadry Z, Northup PG, Stine JG. Inherited thrombophilia and portal vein thrombosis in cirrhosis: a systematic review and meta-analysis. Res Pract Thromb Haemost 2019; 3 (04) 658-667
- 27 Rodriguez-Castro KI, Vitale A, Fadin M. , et al. A prediction model for successful anticoagulation in cirrhotic portal vein thrombosis. Eur J Gastroenterol Hepatol 2019; 31 (01) 34-42
- 28 Mangia A, Margaglione M, Cascavilla I. , et al. Anticardiolipin antibodies in patients with liver disease. Am J Gastroenterol 1999; 94 (10) 2983-2987
- 29 Basili S, Carnevale R, Nocella C. , et al; PRO LIVER Collaborators. Serum albumin is inversely associated with portal vein thrombosis in cirrhosis. Hepatol Commun 2019; 3 (04) 504-512
- 30 Yerdel MA, Gunson B, Mirza D. , et al. Portal vein thrombosis in adults undergoing liver transplantation: risk factors, screening, management, and outcome. Transplantation 2000; 69 (09) 1873-1881
- 31 Stine JG, Argo CK, Pelletier SJ, Maluf DG, Caldwell SH, Northup PG. Advanced non-alcoholic steatohepatitis cirrhosis: a high-risk population for pre-liver transplant portal vein thrombosis. World J Hepatol 2017; 9 (03) 139-146
- 32 Hernández-Conde M, Llop E, Fernández-Carrillo C. , et al. Visceral fat is associated with cirrhotic portal vein thrombosis. Expert Rev Gastroenterol Hepatol 2019; 13 (10) 1017-1022
- 33 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 Hepatol 2015; 63 (03) 743-752
- 34 Sarin SK, Philips CA, Kamath PS. , et al. Toward a comprehensive new classification of portal vein thrombosis in patients with cirrhosis. Gastroenterology 2016; 151 (04) 574-577.e3
- 35 Bhangui P, Lim C, Levesque E. , et al. Novel classification of non-malignant portal vein thrombosis: a guide to surgical decision-making during liver transplantation. J Hepatol 2019; 71 (05) 1038-1050
- 36 Englesbe MJ, Kubus J, Muhammad W. , et al. Portal vein thrombosis and survival in patients with cirrhosis. Liver Transpl 2010; 16 (01) 83-90
- 37 Zanetto A, Rodriguez-Kastro KI, Germani G. , et al. Mortality in liver transplant recipients with portal vein thrombosis - an updated meta-analysis. Transpl Int 2018; 31 (12) 1318-1329
- 38 Rodríguez-Castro KI, Porte RJ, Nadal E, Germani G, Burra P, Senzolo M. Management of nonneoplastic portal vein thrombosis in the setting of liver transplantation: a systematic review. Transplantation 2012; 94 (11) 1145-1153
- 39 Mancuso A. Management of portal vein thrombosis in cirrhosis: an update. Eur J Gastroenterol Hepatol 2016; 28 (07) 739-743
- 40 Intagliata NM, Ferreira CN, Caldwell SH. Anticoagulation for portal vein thrombosis in cirrhosis. Clin Liver Dis (Hoboken) 2016; 7 (06) 126-131
- 41 Qi X, Guo X, Yoshida EM. , et al. Transient portal vein thrombosis in liver cirrhosis. BMC Med 2018; 16 (01) 83
- 42 Loffredo L, Pastori D, Farcomeni A, Violi F. Effects of anticoagulants in patients with cirrhosis and portal vein thrombosis: a systematic review and meta-analysis. Gastroenterology 2017; 153 (02) 480-487.e1
- 43 Senzolo M, , M Sartori T, Rossetto V. , et al. Prospective evaluation of anticoagulation and transjugular intrahepatic portosystemic shunt for the management of portal vein thrombosis in cirrhosis. Liver Int 2012; 32 (06) 919-927
- 44 Luca A, Caruso S, Milazzo M. , et al. Natural course of extrahepatic nonmalignant partial portal vein thrombosis in patients with cirrhosis. Radiology 2012; 265 (01) 124-132
- 45 Qi X, Su C, Ren W. , et al. Association between portal vein thrombosis and risk of bleeding in liver cirrhosis: a systematic review of the literature. Clin Res Hepatol Gastroenterol 2015; 39 (06) 683-691
- 46 D'Amico G, De Franchis R. Cooperative Study Group. Upper digestive bleeding in cirrhosis. Post-therapeutic outcome and prognostic indicators. Hepatology 2003; 38 (03) 599-612
- 47 Dell'Era A, Iannuzzi F, Fabris FM. , et al. Impact of portal vein thrombosis on the efficacy of endoscopic variceal band ligation. Dig Liver Dis 2014; 46 (02) 152-156
- 48 La Mura V, Braham S, Tosetti G. , et al. Harmful and beneficial effects of anticoagulants in patients with cirrhosis and portal vein thrombosis. Clin Gastroenterol Hepatol 2018; 16 (07) 1146-1152.e4
- 49 Pettinari I, Vukotic R, Stefanescu H. , et al; BO-LIVES (BOlogna LIVEr vascular Studies). Clinical impact and safety of anticoagulants for portal vein thrombosis in cirrhosis. Am J Gastroenterol 2019; 114 (02) 258-266
- 50 Cerini F, Vilaseca M, Lafoz E. , et al. Enoxaparin reduces hepatic vascular resistance and portal pressure in cirrhotic rats. J Hepatol 2016; 64 (04) 834-842
- 51 Vilaseca M, García-Calderó H, Lafoz E. , et al. The anticoagulant rivaroxaban lowers portal hypertension in cirrhotic rats mainly by deactivating hepatic stellate cells. Hepatology 2017; 65 (06) 2031-2044
- 52 Villa E, Cammà C, Marietta M. , et al. Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis. Gastroenterology 2012; 143 (05) 1253-1260.e4
- 53 Amitrano L, Guardascione MA, Menchise A. , et al. Safety and efficacy of anticoagulation therapy with low molecular weight heparin for portal vein thrombosis in patients with liver cirrhosis. J Clin Gastroenterol 2010; 44 (06) 448-451
- 54 Artaza T, Lopes M, Romero M. , et al. Efficacy and safety of anticoagulation in non-malignant portal vein thrombosis in patients with liver cirrhosis. Gastroenterol Hepatol 2018; 41 (10) 611-617
- 55 Delgado MG, Seijo S, Yepes I. , et al. Efficacy and safety of anticoagulation on patients with cirrhosis and portal vein thrombosis. Clin Gastroenterol Hepatol 2012; 10 (07) 776-783
- 56 Bergère M, Erard-Poinsot D, Boillot O. , et al. Portal vein thrombosis and liver cirrhosis: Long-term anticoagulation is effective and safe. Clin Res Hepatol Gastroenterol 2019; 43 (04) 395-402
- 57 Werner KT, Sando S, Carey EJ. , et al. Portal vein thrombosis in patients with end stage liver disease awaiting liver transplantation: outcome of anticoagulation. Dig Dis Sci 2013; 58 (06) 1776-1780
- 58 Hanafy AS, Abd-Elsalam S, Dawoud MM. Randomized controlled trial of rivaroxaban versus warfarin in the management of acute non-neoplastic portal vein thrombosis. Vascul Pharmacol 2019; 113: 86-91
- 59 Chung JWH, Kim GH, Lee JHO. , et al. Safety, efficacy, and response predictors of anticoagulation for the treatment of nonmalignant portal-vein thrombosis in patients with cirrhosis: a propensity score matching analysis. Clin Mol Hepatol 2014; 20 (04) 384-391
- 60 Cui SB, Shu RH, Yan SP. , et al. Efficacy and safety of anticoagulation therapy with different doses of enoxaparin for portal vein thrombosis in cirrhotic patients with hepatitis B. Eur J Gastroenterol Hepatol 2015; 27 (08) 914-919
- 61 Condat B, Pessione F, Helene Denninger M, Hillaire S, Valla D. Recent portal or mesenteric venous thrombosis: increased recognition and frequent recanalization on anticoagulant therapy. Hepatology 2000; 32 (03) 466-470
- 62 Chen H, Liu L, Qi X. , et al. Efficacy and safety of anticoagulation in more advanced portal vein thrombosis in patients with liver cirrhosis. Eur J Gastroenterol Hepatol 2016; 28 (01) 82-89
- 63 Intagliata NM, Argo CK, Stine JG, Lisman T, Caldwell SH, Violi F. faculty of the 7th International Coagulation in Liver Disease. Concepts and controversies in haemostasis and thrombosis associated with liver disease: proceedings of the 7th International Coagulation in Liver Disease Conference. Thromb Haemost 2018; 118 (08) 1491-1506
- 64 Intagliata NM, Henry ZH, Maitland H. , et al. Direct oral anticoagulants in cirrhosis patients pose similar risks of bleeding when compared to traditional anticoagulation. Dig Dis Sci 2016; 61 (06) 1721-1727
- 65 Martinez M, Tandra A, Vuppalanchi R. Treatment of acute portal vein thrombosis by nontraditional anticoagulation. Hepatology 2014; 60 (01) 425-426
- 66 Xu X, Guo X, Wang R. , et al. Low-molecular-weight heparin followed by rivaroxaban for acute occlusive portomesenteric vein thrombosis in a cirrhotic patient treated with multiple endoscopic variceal procedures. Ann Hepatol 2019; DOI: 10.1016/j.aohep.2019.08.002. (epub ahead of print)
- 67 Yang H, Kim SR, Song MJ. Recurrent acute portal vein thrombosis in liver cirrhosis treated by rivaroxaban. Clin Mol Hepatol 2016; 22 (04) 499-502
- 68 De Gottardi A, Trebicka J, Klinger C. , et al; VALDIG Investigators. Antithrombotic treatment with direct-acting oral anticoagulants in patients with splanchnic vein thrombosis and cirrhosis. Liver Int 2017; 37 (05) 694-699
- 69 Cerini F, Gonzalez JM, Torres F. , et al. Impact of anticoagulation on upper-gastrointestinal bleeding in cirrhosis. A retrospective multicenter study. Hepatology 2015; 62 (02) 575-583
- 70 Senzolo M, Riva N, Dentali F. , et al; IRSVT Study Investigators. Long-term outcome of splanchnic vein thrombosis in cirrhosis. Clin Transl Gastroenterol 2018; 9 (08) 176
- 71 Hoolwerf EW, Kraaijpoel N, Büller HR, van Es N. Direct oral anticoagulants in patients with liver cirrhosis: a systematic review. Thromb Res 2018; 170: 102-108
- 72 Elhosseiny S, Al Moussawi H, Chalhoub JM, Lafferty J, Deeb L. Direct oral anticoagulants in cirrhotic patients: current evidence and clinical observations. Can J Gastroenterol Hepatol 2019; 4383269
- 73 Hum J, Shatzel JJ, Jou JH, Deloughery TG. The efficacy and safety of direct oral anticoagulants vs traditional anticoagulants in cirrhosis. Eur J Haematol 2017; 98 (04) 393-397
- 74 Priyanka P, Kupec JT, Krafft M, Shah NA, Reynolds GJ. Newer oral anticoagulants in the treatment of acute portal vein thrombosis in patients with and without cirrhosis. Int J Hepatol 2018; 2018:8432781
- 75 Bianchini M, Cavani G, Bonaccorso A. , et al. Low molecular weight heparin does not increase bleeding and mortality post-endoscopic variceal band ligation in cirrhotic patients. Liver Int 2018; 38 (07) 1253-1262
- 76 Maruyama H, Takahashi M, Shimada T, Yokosuka O. Emergency anticoagulation treatment for cirrhosis patients with portal vein thrombosis and acute variceal bleeding. Scand J Gastroenterol 2012; 47 (06) 686-691
- 77 Rodrigues SG, Sixt S, Abraldes JG. , et al. Systematic review with meta-analysis: portal vein recanalisation and transjugular intrahepatic portosystemic shunt for portal vein thrombosis. Aliment Pharmacol Ther 2019; 49 (01) 20-30
- 78 Thornburg B, Desai K, Hickey R. , et al. Pretransplantation portal vein recanalization and transjugular intrahepatic portosystemic shunt creation for chronic portal vein thrombosis: final analysis of a 61-patient cohort. J Vasc Interv Radiol 2017; 28 (12) 1714-1721.e2
- 79 Han G, Qi X, He C. , et al. Transjugular intrahepatic portosystemic shunt for portal vein thrombosis with symptomatic portal hypertension in liver cirrhosis. J Hepatol 2011; 54 (01) 78-88
- 80 Salem R, Vouche M, Baker T. , et al. Pretransplant portal vein recanalization-transjugular intrahepatic portosystemic shunt in patients with complete obliterative portal vein thrombosis. Transplantation 2015; 99 (11) 2347-2355
- 81 Kallini JR, Gabr A, Kulik L. , et al. Noncirrhotic complete obliterative portal vein thrombosis: Novel management using trans-splenic transjugular intrahepatic portosystemic shunt with portal vein recanalization. Hepatology 2016; 63 (04) 1387-1390
- 82 Madoff DC, Gaba RC, Weber CN, Clark TWI, Saad WE. Portal venous interventions: state of the art. Radiology 2016; 278 (02) 333-353
- 83 Klinger C, Riecken B, Schmidt A. , et al. Transjugular portal vein recanalization with creation of intrahepatic portosystemic shunt (PVR-TIPS) in patients with chronic non-cirrhotic, non-malignant portal vein thrombosis. Z Gastroenterol 2018; 56 (03) 221-237
- 84 Luca A, Miraglia R, Caruso S. , et al. Short- and long-term effects of the transjugular intrahepatic portosystemic shunt on portal vein thrombosis in patients with cirrhosis. Gut 2011; 60 (06) 846-852
- 85 Wang Z, Jiang MS, Zhang HL. , et al. Is post-TIPS anticoagulation therapy necessary in patients with cirrhosis and portal vein thrombosis? A randomized controlled trial. Radiology 2016; 279 (03) 943-951