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2017, Number 4

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Ann Hepatol 2017; 16 (4)

Non-neoplastic Portal Vein Thrombosis in HCV Cirrhosis Patients: is it an Immuno-Inflammatory Disorder?

Abu El-Makarem MA, El-Akad AF, Elian MM, Sherif TM, El-shaheed RA, Abd EL Fatah AS, Sayed DM, Bakry RM, Mahmoud AM

Language: English
References: 50
Page: 574-583
PDF size: 211.73 Kb.


ABSTRACT

Background and aims. Portal vein thrombosis (PVT) is a critical complication in cirrhotic patients. We explored the role of the activated factor VII-antithrombin (FVIIa-AT) complex and enhanced monocytic tissue factor (TF) expression in the development and prediction of non-neoplastic PVT in cirrhotic patients. Material and methods. A total of 30 HCV-cirrhosis patients were included in our study. They were compared to 35 cirrhotic patients without PVT, 15 non-cirrhotic patients with PVT, and 15 healthy controls. The plasma level of the FVIIa-AT complexes was analyzed by ELISA. MIF CD142, CD86, and HLA-DR on monocytes (CD14) were determined by flow cytometry. Results. Compared with cirrhotic patients without PVT, cirrhotic patients with PVT had comparable plasma values of FVIIa, AT, and the FVIIa-AT complex. However, they had significantly lower values compared to non-cirrhotic patients with PVT and healthy controls. Cirrhotic patients with PVT had increased monocytic TF expression (MIF CD142) compared to non-PVT cirrhotic patients and healthy controls [86.5 (93.5) vs. 18 (32.0) and 11.0 (6.0), respectively; p ‹ 0.001 for each]. However, cirrhosis PVT could not be distinguished from non-cirrhosis PVT. The area under the ROC curve of MIF CD142 was 0.759 (0.641- 0.876; p = 0.000) at an optimal cut-off value of 45, which yielded a sensitivity of 60% and a specificity of 77.1%, as well as a PPV and NPV of 69.2% for each. Conclusion. Enhanced expression of monocytic TF may have a role in the development and prediction of non-neoplastic PVT in HCV-cirrhosis patients. Large multicenter studies are necessary to validate our results.


REFERENCES

  1. Amitrano L, Brancaccio V, Guardascione MA, Margaglione M, Iannaccone L, D'Andrea G, Marmo R, et al. Inherited coagulation disorders in cirrhotic patients with portal vein thrombosis. Hepatol 2000; 31:345-8.

  2. Francoz C, Belghiti J, Vilgrain V, Sommacale D, Paradis V, Condat B, Denninger MH, et al. Splanchnic vein thrombosis in candidates for liver transplantation: usefulness of screening and anticoagulation. Gut 2005; 54: 691-7.

  3. Hoekstra J, Janssen HL. Vascular liver disorders (II): portal vein thrombosis. Neth J Med 2009; 67: 46-53.

  4. Zocco M A, Di Stasio E, De Cristofaro R, Novi M, Ainora ME, Ponziani F, Riccardi L, et al. Thrombotic risk factors in patients with liver cirrhosis: correlation with MELD scoring system and portal vein thrombosis development. J Hepatol 2009; 51: 682-9.

  5. Ponziani FR, Zocco MA, Campanale C, Rinninella E, Tortora A, Di Maurizio L, Bombardieri G, et al. Portal vein thrombosis insight into physiopathology, diagnosis, and treatment. WJG 2010; 16: 143-55.

  6. Caldwell SH, Hoffman M, Lisman T, Macik BG, Northup PG, Reddy KR, Tripodi A, et al. Coagulation disorders and haemostasis in liver disease: pathophysiology and critical assessment of current management. Hepatology 2006; 44: 1039-46.

  7. Marchetti M, Russo L, Tartari CJ, Woodhams B, Rossi G, Di Bona E, Rambaldi A, et al. Evaluation of severe thromb- hemorrhagic syndrome by assessing levels of activated FVII-antithrombin complex and tissue factor mRNA in acute promyelocytic leukemia patients. Abstract 18th Congress of the European Hematology Association. Haematologica 2013; SI: S614.

  8. Spiezia L, Rossetto V, Campello E, Gavasso S, Woodhams B, Tormene D, Simioni P. Factor VIIa- antithrombin complexes in patients with arterial and venous thrombosis. Thromb Haemost 2010; 103: 1188-92.

  9. Bajaj MS, Birktoft JJ, Steer SA, Bajaj SP. Structure and biology of tissue factor pathway inhibitor. Thromb Haemost 2001; 86: 959-72.

  10. Bazan JE. Structural design and molecular evaluation of a cytokine receptor superfamily. Proc Natl Acad Sci USA 1990; 87: 6934-38.

  11. Ruf W, Riewald M. Tissue factor- dependent coagulation pretense signaling in acute lung injury. Crit Care Med 2003; 31: S231-S237.

  12. Baroni M, Pizzirani C, Pinotti M, Ferrari D, Adinolfi E, Calzavarini S, Caruso P, et al. Stimulation of P2 (P2X7) receptors in human dendritic cells induces the release of tissue factorbearing microparticles. FASEB J 2007; 21: 1926-33.

  13. Owens A Ph, Mackman N, Weber C, Mouse S. Microparticles in hemostasis and thrombosis. Circul Res 2011; 108: 1284-97.

  14. Aleman MM, Gardiner C, Harrison P, Wolberg AS. Differential Contributions of Monocyte- and Platelet-derived Microparticles towards Thrombin Generation and Fibrin Formation and Stability. J Thromb Haemost 2011; 9: 2251-61.

  15. Spiezia L, Campello E, Gentilomo C, Gavasso S, Woodhams B, Laverda AM, Simioni P, et al. Factor VIIa-antithrombin complexes in children with ischemic stroke. Thromb Res 2011; 128: 303-4.

  16. Silveira A, Scanavini D, Boquist S, Ericsson C-G, Hellénius M-L, Leander K, de Faire U, et al. Relationships of plasma factor VIIa-antithrombin complexes to manifest and future cardiovascular disease. Thromb Res 2012; 130: 221-5.

  17. Martinelli N, Girelli D, Baroni M, Guarini P, Sandri M, Lunghi B, Tosi F, et al. Activated factor VII-antithrombin complex predicts mortality in patients with stable coronary artery disease: a cohort study. J Thromb Haemost 2016; 14: 655-66.

  18. Sample size project by Philippe Glaziou 2003. Available at http://sampsize.sourceforge.net/.

  19. Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology 1996; 24: 289-93.

  20. Centers for Disease Control. Taiwan 2007. Available at http:/ /wwwcdcgov

  21. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diab Care 2004; 27: S5-S10.

  22. Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 1973; 60: 646-9.

  23. Kamath PS, Wiesner RH, Malinchoc M, Kremers W, Therneau TM, Kosberg CL, D'Amico G, et al. A model to predict survival in patients with end-stage liver disease. Hepatology 2001; 33: 464-70.

  24. Abu El Makarem MA, Eslam M, Sayed D, Shawkat M, Idriss NK, Soliman EM, Sherif T, et al. Diabetes worsening of hepatitis C cirrhosis: Are alterations in monocytic tissue factor (CD142) is the cause? Ann Hepatol 2014; 13: 27-37.

  25. Rossetto V, Spiezia L, Senzolo M, Rodriguez K, Gavasso S, Woodhams B, Simioni P. Factor VIIa-antithrombin complexes in patients with non-neoplastic portal vein thrombosis with and without cirrhosis. Int J Lab Hematol 2013; 35: 101-5.

  26. Campo G, Valgimigli M, Ferraresi P, Malagutti P, Baroni M, Acrozzi C, Gemmati D, et al. Tissue factor and coagulation factor VII levels during acute myocardial infarction: association with genotype and adverse events. Arterioscler Thromb Vasc Biol 2006; 26: 2800-6.

  27. Tripodi A, Salerno F, Chantarangkul V, Clerici M, Cazzanig M, Pnmignani M, Mannucci PM. Evidence of normal thrombin generation in cirrhosis depite abnormal conventional coagulation tests. Hepatology 2005; 41: 553-8.

  28. Tripodi A. Tests of coagulation in liver disease. Clin Liver Dis 2009; 13: 55-61.

  29. Sangaletti S, Tripodo C, Chiodoni C, Guarnotta C, Cappetti B, Casalini P, Piconese S, et al. Neutrophil extracellular traps mediate transfer of cytoplasmic neutrophil antigens to myeloid dendritic cells towards ANCA induction and associated autoimmunity. Blood 2012; 120: 3007-18.

  30. Rautou PE, Bresson J, Sainte-Marie Y, Vion AC, Paradis V, Renard JM, Devue C, et al. Abnormal plasma microparticles impair vasoconstrictor responses in patients with cirrhosis. Gastroenterology 2012; 143: 166-76.

  31. Echeverria C, Montorfano I, Tapia P, Riedel C, Cabello-Verrugio C, Simon F. Endotoxin-induced endothelial fibrosis is dependent on expression of transforming growth factors 1 and 2. Infect Immun 2014; 82: 3678-86.

  32. Coughlin SR. Protease-activated receptors in hemostasis, thrombosis and vascular biology. J Thromb Haemost 2005; 3: 1800-14.

  33. Coughlin SR. Thrombin signaling and protease activated receptors. Nature 2000; 407: 258-64.

  34. Tripodi A, Anstee QM, Sogaard KK, Primignani M, Valla DC. Hypercoagulbility in cirrhosis: causes and consequences. J Thromb Haemost 2011; 9: 1713-23.

  35. Lamps LW, Hunt CM, Green A, Gray GF Jr, Washington K. Alterations in colonic mucosal vessels in patients with cirrhosis and noncirrhotic portal hypertension. Hum Pathol 1998; 29: 527-35.

  36. Berg R. Bacterial translocation from the gastrointestinal tract. Trends Microbiol 1995; 3: 149-54.

  37. Blackwell TS, Christman JW. Sepsis and cytokines: current status. Br J Anaesth 1996; 77: 110-17.

  38. Haveman JW, Muller Kobold AC, Tervaert JW, van den Berg AP, Tulleken JE, Kallenberg CG, The TH. The central role of monocytes in the pathogenesis of sepsis: consequences for immunomonitoring and treatment. Neth J Med 1999; 55: 132-41.

  39. Sipeki N, Antal-Szalmas P, Lakatos PL, Papp M. Immune dysfunction in cirrhosis. WJG 2014; 20: 2564-77.

  40. Barcy S, Wettendorff M, Leo O, Urbain J, Kruger M, Ceuppens JL, de Boer M. FcR cross-linking on monocytes results in impaired T cell stimulatory capacity. Int Immunol 1995; 7: 179-89.

  41. Zheng Y, Manzotti CN, Liu M, Burke F, Mead KI, Sansom DM. CD86 and CD80 differentially modulate the suppressive function of human regulatory T cells. J Immunol 2004; 172: 2778-84.

  42. de Franchis R, Primignani M. Natural history of portal hypertension in patients with cirrhosis. Clin Liver Dis 2001; 5: 645-63.

  43. Kinjo N, Kawanaka H, Akahoshi T, Tomikawa M, Yamashita N, Konishi K, Tanoue K, et al. Risk factors for portal venous thrombosis after splenectomy in patients with cirrhosis and portal hypertension. Br J Surg 2010; 910-6.

  44. Rockey DC, Housset CN, Friedman SL. Activation-dependent contractivity of rat hepatic lipocytes in culture and in vivo. J Clin Invest 1993; 92: 1795-804.

  45. Schwabe RF, Seki E, Brenner DA. Toll-like receptor signaling in the liver. Gastroenterology 2006; 130:1886-900.

  46. Jagavelu R, Routray C, Shergill U, O'Hara SP, Faubion W, Shah VH. Endothelial cell toll-like receptor 4 regulates fibrosis- associated angiogenesis in the liver. Hepatology 2010; 52: 590-601.

  47. Seo YS, Kwon JH, Yaqoob U, Yang L, De Assuncao TM, Simonetto DA, Verma VK, et al. HMGB1 recruits HSCs and liver endothelial cells to sites of ethanol- induced parenchymal cell injury. Am J Physiol Gastrointest Liver Physiol 2013; 305: G838-G848.

  48. Pagliaro L, D'Amico G, Luca A, Pasta L, Politi F, Aragona E, Malizia G. Portal hypertension: diagnosis and treatment. J Hepatol 1995; 23: 36-44.

  49. Samuel H, Nardi M, Karpatkin M, Hart D, Belmont M, Karpatkin S. Differentiation of autoimmune thrombocytopenia from thrombocytopenia associated with immune complex disease: systemic lupus erythematosus, hepatitis-cirrhosis, and HIV-1 infection by platelet and serum immunological measurements. Br J Haematol 1999; 105: 1086-91.

  50. Okubo M, Shiota G, Kawasaki H. Thrombopoietin levels in serum and liver tissue in patients with chronic viral hepatitis and hepatocellular carcinoma. Clin Sci (Lond) 2000; 99: 207-14.




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