Figure 1. Flow chart
Figure 2. Portal vein recanalization during follow-up
Complete (n=12)!
38%
Partial (n=11) 34%
None (n=9) 28%
Patients!with!
cirrhosis!and!portal!
vein!thrombosis n!=!88
Excluded:!
! Not!treated!with!
anticoagulation!n!=!20
! Treated!with!anticoagulation,!
but!without!variceal!band!
ligation!n!=!36
!
Included!patients n!=!32
Table&1&Characteristics!of!the!32!patients!at!first!endoscopic!band!ligation!
!! Prothrombin!(%)!
Table2.!Events!during!followOup!
Table!3.!Characteristic!of!the!3!patients!who!developed!an!upper!gastrointestinal!bleeding!attributed!to!
Table!4.!Comparison!of!patients!developing!an!upper!gastrointestinal!bleeding!attributed!to!previous!
7. ! Discussion et conclusion
Dans ce travail, nous mettons en avant et tentons d’éclaircir le paradoxe du malade atteint de cirrhose. D’un côté le risque hémorragique principalement médié par l’hypertension portale et le développement des varices oesophagiennes, de l’autre le risque thrombotique et le développement notamment de thrombose de la veine porte. Ces deux risques opposés sont associés aux changements hémodynamiques et biologiques engendrés par la cirrhose.
Il est à présent clair que les malades présentant des varices à risque de saignement doivent bénéficier soit d’un traitement par bêta-bloqueur non sélectif soit de séance de ligatures. Il est également clairement indiqué de traiter par anticoagulant les patients atteints de cirrhose présentant une thrombose de la veine porte. Notre étude avait pour but d’étudier la sécurité des ligatures de varices oesophagiennes chez les malades anticoagulés pour une thrombose de la veine porte tant dans un contexte de prévention primaire que secondaire. Nous avons identifié 3 patients sur 32 ayant présenté un saignement post séance de ligature de varices oesophagiennes.
Aucun de ces évènements n’a engendré un décès ou une choc hémorragique. Nous avons pu identifier deux facteurs de risque associés à la survenue de saignement après séance de ligatures : antécédent de décompensation cirrhotique et antécédent de rupture de varices oesophagiennes (p=0.03 et p=0.05 respectivement).
Nos résultats suggèrent que les ligatures de varices oesophagiennes chez les patients atteints de cirrhose et anticoagulés pour une thrombose de la veine porte semblent engendrer un faible risque de saignement post procédure. Dans ce contexte, le traitement anticoagulant chez ces patients ne devrait pas être arrêté ni introduit tardivement en raison de séances de ligatures à venir. Inversement, les ligatures de varices oesophagiennes ne devraient pas être retardées en raison d’un traitement anticoagulant en cours pour une thrombose de la veine porte.
8. ! Références
1. Germani G, Hytiroglou P, Fotiadu A, Burroughs AK, Dhillon AP. Assessment of fibrosis and cirrhosis in liver biopsies: an update. Semin Liver Dis. 2011 Feb;31(1):82–90.
2. Campana L, Iredale JP. Regression of Liver Fibrosis. Semin Liver Dis. 2017;37(1):1–
10.
3. Scaglione S, Kliethermes S, Cao G, Shoham D, Durazo R, Luke A, et al. The Epidemiology of Cirrhosis in the United States: A Population-based Study. J Clin Gastroenterol. 2015 Sep;49(8):690–6.
4. Ge PS, Runyon BA. Treatment of Patients with Cirrhosis. N Engl J Med. 2016 Aug 25;375(8):767–77.
5. El Khoury AC, Klimack WK, Wallace C, Razavi H. Economic burden of hepatitis C-associated diseases in the United States. J Viral Hepat. 2012 Mar;19(3):153–60.
6. Nery F, Chevret S, Condat B, de Raucourt E, Boudaoud L, Rautou P-E, et al. Causes and consequences of portal vein thrombosis in 1,243 patients with cirrhosis: results of a longitudinal study. Hepatol Baltim Md. 2015 Feb;61(2):660–7.
7. Godat S, Antonino AT, Dehlavi M-A, Moradpour D, Doerig C. [Management of ascites due to portal hypertension]. Rev Med Suisse. 2012 Sep 5;8(352):1665–8.
8. Sanyal AJ, Bosch J, Blei A, Arroyo V. Portal hypertension and its complications.
Gastroenterology. 2008 May;134(6):1715–28.
9. Bataller R, Sancho-Bru P, Ginès P, Lora JM, Al-Garawi A, Solé M, et al. Activated human hepatic stellate cells express the renin-angiotensin system and synthesize angiotensin II. Gastroenterology. 2003 Jul;125(1):117–25.
10. Gupta TK, Toruner M, Chung MK, Groszmann RJ. Endothelial dysfunction and decreased production of nitric oxide in the intrahepatic microcirculation of cirrhotic rats.
Hepatol Baltim Md. 1998 Oct;28(4):926–31.
11. Pizcueta MP, Piqué JM, Bosch J, Whittle BJ, Moncada S. Effects of inhibiting nitric oxide biosynthesis on the systemic and splanchnic circulation of rats with portal hypertension. Br J Pharmacol. 1992 Jan;105(1):184–90.
12. Abraldes JG, Iwakiri Y, Loureiro-Silva M, Haq O, Sessa WC, Groszmann RJ. Mild increases in portal pressure upregulate vascular endothelial growth factor and endothelial nitric oxide synthase in the intestinal microcirculatory bed, leading to a hyperdynamic state. Am J Physiol Gastrointest Liver Physiol. 2006 May;290(5):G980-987.
13. D’Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol. 2006 Jan;44(1):217–31.
14. Shibuya M. Vascular endothelial growth factor and its receptor system:
physiological functions in angiogenesis and pathological roles in various diseases. J Biochem (Tokyo). 2013 Jan;153(1):13–9.
15. Fernandez M, Mejias M, Angermayr B, Garcia-Pagan JC, Rodés J, Bosch J.
Inhibition of VEGF receptor-2 decreases the development of hyperdynamic splanchnic circulation and portal-systemic collateral vessels in portal hypertensive rats. J Hepatol.
2005 Jul;43(1):98–103.
16. Fernandez M, Vizzutti F, Garcia-Pagan JC, Rodes J, Bosch J. Anti-VEGF receptor-2 monoclonal antibody prevents portal-systemic collateral vessel formation in portal hypertensive mice. Gastroenterology. 2004 Mar;126(3):886–94.
17. Garcia-Tsao G, Abraldes JG, Berzigotti A, Bosch J. Portal hypertensive bleeding in cirrhosis: Risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases. Hepatology. 2017 Jan 1;65(1):310–35.
18. Kovalak M, Lake J, Mattek N, Eisen G, Lieberman D, Zaman A. Endoscopic screening for varices in cirrhotic patients: data from a national endoscopic database.
Gastrointest Endosc. 2007 Jan;65(1):82–8.
19. Merli M, Nicolini G, Angeloni S, Rinaldi V, De Santis A, Merkel C, et al. Incidence and natural history of small esophageal varices in cirrhotic patients. J Hepatol. 2003 Mar;38(3):266–72.
20. Garcia-Tsao G, Groszmann RJ, Fisher RL, Conn HO, Atterbury CE, Glickman M.
Portal pressure, presence of gastroesophageal varices and variceal bleeding. Hepatol Baltim Md. 1985 Jun;5(3):419–24.
21. North Italian Endoscopic Club for the Study and Treatment of Esophageal Varices.
Prediction of the first variceal hemorrhage in patients with cirrhosis of the liver and esophageal varices. A prospective multicenter study. N Engl J Med. 1988 Oct 13;319(15):983–9.
22. D’Amico G, Pagliaro L, Bosch J. Pharmacological treatment of portal hypertension:
an evidence-based approach. Semin Liver Dis. 1999;19(4):475–505.
23. Reverter E, Tandon P, Augustin S, Turon F, Casu S, Bastiampillai R, et al. A MELD-based model to determine risk of mortality among patients with acute variceal bleeding.
Gastroenterology. 2014 Feb;146(2):412-419.e3.
24. de Franchis R. Evaluation and follow-up of patients with cirrhosis and oesophageal varices. J Hepatol. 2003 Mar;38(3):361–3.
25. de Franchis R, Primignani M. Natural history of portal hypertension in patients with cirrhosis. Clin Liver Dis. 2001 Aug;5(3):645–63.
26. Groszmann RJ, Bosch J, Grace ND, Conn HO, Garcia-Tsao G, Navasa M, et al.
Hemodynamic events in a prospective randomized trial of propranolol versus placebo in the prevention of a first variceal hemorrhage. Gastroenterology. 1990 Nov;99(5):1401–7.
27. Khuroo MS, Khuroo NS, Farahat KLC, Khuroo YS, Sofi AA, Dahab ST. Meta-analysis:
endoscopic variceal ligation for primary prophylaxis of oesophageal variceal bleeding.
Aliment Pharmacol Ther. 2005 Feb 15;21(4):347–61.
28. Smalberg JH, Arends LR, Valla DC, Kiladjian J-J, Janssen HLA, Leebeek FWG.
Myeloproliferative neoplasms in Budd-Chiari syndrome and portal vein thrombosis: a meta-analysis. Blood. 2012 Dec 13;120(25):4921–8.
29. Chait Y, Condat B, Cazals-Hatem D, Rufat P, Atmani S, Chaoui D, et al. Relevance of the criteria commonly used to diagnose myeloproliferative disorder in patients with splanchnic vein thrombosis. Br J Haematol. 2005 May;129(4):553–60.
30. Plessier A, Darwish-Murad S, Hernandez-Guerra M, Consigny Y, Fabris F, Trebicka J, et al. Acute portal vein thrombosis unrelated to cirrhosis: a prospective multicenter follow-up study. Hepatol Baltim Md. 2010 Jan;51(1):210–8.
31. Qi X, De Stefano V, Su C, Bai M, Guo X, Fan D. Associations of antiphospholipid antibodies with splanchnic vein thrombosis: a systematic review with meta-analysis.
Medicine (Baltimore). 2015 Jan;94(4):e496.
32. Justo D, Finn T, Atzmony L, Guy N, Steinvil A. Thrombosis associated with acute cytomegalovirus infection: a meta-analysis. Eur J Intern Med. 2011 Apr;22(2):195–9.
33. Janssen HL, Meinardi JR, Vleggaar FP, van Uum SH, Haagsma EB, van Der Meer FJ, et al. Factor V Leiden mutation, prothrombin gene mutation, and deficiencies in coagulation inhibitors associated with Budd-Chiari syndrome and portal vein thrombosis:
results of a case-control study. Blood. 2000 Oct 1;96(7):2364–8.
34. Clavien PA, Huber O, Rohner A. Venous mesenteric ischaemia: conservative or surgical treatment? Lancet Lond Engl. 1989 Jul 1;2(8653):48.
35. Amitrano L, Guardascione MA, Scaglione M, Pezzullo L, Sangiuliano N, Armellino MF, et al. Prognostic factors in noncirrhotic patients with splanchnic vein thromboses. Am J Gastroenterol. 2007 Nov;102(11):2464–70.
36. Ogren M, Bergqvist D, Björck M, Acosta S, Eriksson H, Sternby NH. Portal vein thrombosis: prevalence, patient characteristics and lifetime risk: a population study based on 23,796 consecutive autopsies. World J Gastroenterol. 2006 Apr 7;12(13):2115–9.
37. Francoz C, Valla D, Durand F. Portal vein thrombosis, cirrhosis, and liver transplantation. J Hepatol. 2012 Jul;57(1):203–12.
38. 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 Apr;108(4):568–74.
39. Englesbe MJ, Schaubel DE, Cai S, Guidinger MK, Merion RM. Portal vein thrombosis and liver transplant survival benefit. Liver Transplant Off Publ Am Assoc Study Liver Dis Int Liver Transplant Soc. 2010 Aug;16(8):999–1005.
40. Amitrano L, Guardascione MA, Brancaccio V, Margaglione M, Manguso F, Iannaccone L, et al. Risk factors and clinical presentation of portal vein thrombosis in patients with liver cirrhosis. J Hepatol. 2004 May;40(5):736–41.
41. Villa E, Cammà C, Marietta M, Luongo M, Critelli R, Colopi S, et al. Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis. Gastroenterology. 2012 Nov;143(5):1253-1260.e1-4.
42. Delgado MG, Seijo S, Yepes I, Achécar L, Catalina MV, García-Criado A, et al.
Efficacy and safety of anticoagulation on patients with cirrhosis and portal vein thrombosis. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2012 Jul;10(7):776–83.
43. Goulis J, Chau TN, Jordan S, Mehta AB, Watkinson A, Rolles K, et al.
Thrombopoietin concentrations are low in patients with cirrhosis and thrombocytopenia and are restored after orthotopic liver transplantation. Gut. 1999 May;44(5):754–8.
44. Witters P, Freson K, Verslype C, Peerlinck K, Hoylaerts M, Nevens F, et al. Review article: blood platelet number and function in chronic liver disease and cirrhosis. Aliment Pharmacol Ther. 2008 Jun 1;27(11):1017–29.
45. Ditisheim S, Goossens N, Spahr L, Hadengue A. [Coagulation and cirrhosis: new insight]. Rev Med Suisse. 2012 Sep 5;8(352):1652, 1654–6.
46. Mangia A, Villani MR, Cappucci G, Santoro R, Ricciardi R, Facciorusso D, et al.
Causes of portal venous thrombosis in cirrhotic patients: the role of genetic and acquired factors. Eur J Gastroenterol Hepatol. 2005 Jul;17(7):745–51.
47. Francoz C, Belghiti J, Vilgrain V, Sommacale D, Paradis V, Condat B, et al.
Splanchnic vein thrombosis in candidates for liver transplantation: usefulness of screening and anticoagulation. Gut. 2005 May;54(5):691–7.
48. Chen H, Turon F, Hernández-Gea V, Fuster J, Garcia-Criado A, Barrufet M, et al.
Nontumoral portal vein thrombosis in patients awaiting liver transplantation. Liver Transplant Off Publ Am Assoc Study Liver Dis Int Liver Transplant Soc. 2016 Mar;22(3):352–
65.
49. 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 Aug;153(2):480-487.e1.
50. 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 Sep;63(3):743–52.
51. Cagin YF, Atayan Y, Erdogan MA, Dagtekin F, Colak C. Incidence and clinical presentation of portal vein thrombosis in cirrhotic patients. Hepatobiliary Pancreat Dis Int HBPD INT. 2016 Oct;15(5):499–503.
52. Guillaume M, Christol C, Plessier A, Corbic M, Péron J-M, Sommet A, et al.
Bleeding risk of variceal band ligation in extrahepatic portal vein obstruction is not increased by oral anticoagulation. Eur J Gastroenterol Hepatol. 2018 May;30(5):563–8.
53. Bianchini M, Cavani G, Bonaccorso A, Turco L, Vizzutti F, Sartini A, et al. Low molecular weight heparin does not increase bleeding and mortality post-endoscopic variceal band ligation in cirrhotic patients. Liver Int Off J Int Assoc Study Liver. 2018 Jul;38(7):1253–62.
54. Pugh RNH, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. BJS. 1973 Aug;60(8):646–9.
55. Wiesner RH, McDiarmid SV, Kamath PS, Edwards EB, Malinchoc M, Kremers WK, et al. MELD and PELD: application of survival models to liver allocation. Liver Transplant Off Publ Am Assoc Study Liver Dis Int Liver Transplant Soc. 2001 Jul;7(7):567–80.
56. D’Amico G, Pasta L, Morabito A, D’Amico M, Caltagirone M, Malizia G, et al.
Competing risks and prognostic stages of cirrhosis: a 25-year inception cohort study of 494 patients. Aliment Pharmacol Ther. 2014 May;39(10):1180–93.
57. Idezuki Y. General rules for recording endoscopic findings of esophagogastric varices (1991). Japanese Society for Portal Hypertension. World J Surg. 1995 Jun;19(3):420–2; discussion 423.
58. Sarin SK, Philips CA, Kamath PS, Choudhury A, Maruyama H, Nery FG, et al. Toward a Comprehensive New Classification of Portal Vein Thrombosis in Patients With Cirrhosis.
Gastroenterology. 2016;151(4):574-577.e3.
59. Hwang JH, Shergill AK, Acosta RD, Chandrasekhara V, Chathadi KV, Decker GA, et al. The role of endoscopy in the management of variceal hemorrhage. Gastrointest Endosc. 2014 Aug;80(2):221–7.
60. 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 Jan;26(1):23–9.
61. Cerini F, Gonzalez JM, Torres F, Puente Á, Casas M, Vinaixa C, et al. Impact of anticoagulation on upper-gastrointestinal bleeding in cirrhosis. A retrospective multicenter study. Hepatol Baltim Md. 2015 Aug;62(2):575–83.