Etiology of the Budd-Chiari syndrome
- Michelle Lai, MD, MPH
Michelle Lai, MD, MPH
- Assistant Professor, Harvard Medical School
- Beth Israel Deaconess Medical Center
- Section Editor
- Sanjiv Chopra, MD, MACP
Sanjiv Chopra, MD, MACP
- Editor-in-Chief — Gastroenterology/Hepatology
- Section Editor — General Hepatology; Gallbladder and Biliary Tract Disease
- Professor of Medicine
- Harvard Medical School
- Senior Consultant in Hepatology
- James Tullis Firm Chief
- Beth Israel Deaconess Medical Center
The Budd-Chiari syndrome can be defined as any pathophysiologic process that results in an interruption or diminution of the normal flow of blood out of the liver [1,2]. However, as commonly used, the Budd-Chiari syndrome implies thrombosis of the hepatic veins and/or the intrahepatic or suprahepatic inferior vena cava. An alternative nomenclature that recognizes an obliterative process involving principally the inferior vena cava ("obliterative hepatocavopathy") has also been proposed . The term is usually distinguished from two other conditions that interfere with hepatic venous flow: sinusoidal obstruction syndrome (hepatic veno-occlusive disease) and right heart failure.
●Disorders that involve the microscopic centrilobular veins and small sublobular veins within the liver are usually due to nonthrombotic fibrous occlusion and obliteration of these small veins. The distinct anatomic location, pathology, and conditions (eg, ingestion of toxic pyrrolizidine alkaloids or exposure to high doses of radiation or chemotherapeutic agents) with which sinusoidal obstruction syndrome is associated allow it to be placed in its own category [4,5]. (See "Diagnosis of hepatic sinusoidal obstruction syndrome (veno-occlusive disease) following hematopoietic cell transplantation".)
●Although disorders of the heart may present clinically as the Budd-Chiari syndrome (eg, constrictive pericarditis, chronic right-sided heart failure with severe tricuspid insufficiency), the pathogenesis and treatment of these disorders are quite different from those usually considered typical of the Budd-Chiari syndrome. (See "Congestive hepatopathy".)
Thus, the Budd-Chiari syndrome is due to occlusion or partial occlusion of one, two, or all three of the major hepatic veins (right, middle, and left) and/or occlusion or partial occlusion of the inferior vein cava (figure 1) . In addition, several small veins that enter the inferior vena cava directly from the posterior surface of the caudate lobe and occasionally from the right and left hepatic lobes may or may not be involved by the occlusive process.
This topic review will discuss the major causes of the Budd-Chiari syndrome. The symptoms, diagnosis, and treatment of this disorder are discussed separately. (See "Budd-Chiari syndrome: Epidemiology, clinical manifestations, and diagnosis".)
- Valla DC. Budd-Chiari syndrome and veno-occlusive disease/sinusoidal obstruction syndrome. Gut 2008; 57:1469.
- Menon KV, Shah V, Kamath PS. The Budd-Chiari syndrome. N Engl J Med 2004; 350:578.
- Okuda K, Kage M, Shrestha SM. Proposal of a new nomenclature for Budd-Chiari syndrome: hepatic vein thrombosis versus thrombosis of the inferior vena cava at its hepatic portion. Hepatology 1998; 28:1191.
- Zafrani ES, von Pinaudeau Y, Dhumeaux D. Drug-induced vascular lesions of the liver. Arch Intern Med 1983; 143:495.
- Baglin TP. Veno-occlusive disease of the liver complicating bone marrow transplantation. Bone Marrow Transplant 1994; 13:1.
- Saint-Marc Girardin MF, Zafrani ES, Prigent A, et al. Unilobar small hepatic vein obstruction: possible role of progestogen given as oral contraceptive. Gastroenterology 1983; 84:630.
- Dilawari JB, Bambery P, Chawla Y, et al. Hepatic outflow obstruction (Budd-Chiari syndrome). Experience with 177 patients and a review of the literature. Medicine (Baltimore) 1994; 73:21.
- Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 51-1987. Progressive abdominal distention in a 51-year-old woman with polycythemia vera. N Engl J Med 1987; 317:1587.
- Mitchell MC, Boitnott JK, Kaufman S, et al. Budd-Chiari syndrome: etiology, diagnosis and management. Medicine (Baltimore) 1982; 61:199.
- Powell-Jackson PR, Melia W, Canalese J, et al. Budd-Chiari Syndrome: clinical patterns and therapy. Q J Med 1982; 51:79.
- Gupta S, Blumgart LH, Hodgson HJ. Budd-Chiari syndrome: long-term survival and factors affecting mortality. Q J Med 1986; 60:781.
- Murphy FB, Steinberg HV, Shires GT 3rd, et al. The Budd-Chiari syndrome: a review. AJR Am J Roentgenol 1986; 147:9.
- Maddrey WC. Hepatic vein thrombosis (Budd-Chiari syndrome). Hepatology 1984; 4:44S.
- Darwish Murad S, Plessier A, Hernandez-Guerra M, et al. Etiology, management, and outcome of the Budd-Chiari syndrome. Ann Intern Med 2009; 151:167.
- DeLeve LD, Valla DC, Garcia-Tsao G, American Association for the Study Liver Diseases. Vascular disorders of the liver. Hepatology 2009; 49:1729.
- Hirshberg B, Shouval D, Fibach E, et al. Flow cytometric analysis of autonomous growth of erythroid precursors in liquid culture detects occult polycythemia vera in the Budd-Chiari syndrome. J Hepatol 2000; 32:574.
- Amitrano L, Guardascione MA, Ames PR, et al. Thrombophilic genotypes, natural anticoagulants, and plasma homocysteine in myeloproliferative disorders: relationship with splanchnic vein thrombosis and arterial disease. Am J Hematol 2003; 72:75.
- Primignani M, Barosi G, Bergamaschi G, et al. Role of the JAK2 mutation in the diagnosis of chronic myeloproliferative disorders in splanchnic vein thrombosis. Hepatology 2006; 44:1528.
- Darwish Murad S, Valla DC, de Groen PC, et al. Determinants of survival and the effect of portosystemic shunting in patients with Budd-Chiari syndrome. Hepatology 2004; 39:500.
- Valla D, Casadevall N, Lacombe C, et al. Primary myeloproliferative disorder and hepatic vein thrombosis. A prospective study of erythroid colony formation in vitro in 20 patients with Budd-Chiari syndrome. Ann Intern Med 1985; 103:329.
- Pagliuca A, Mufti GJ, Janossa-Tahernia M, et al. In vitro colony culture and chromosomal studies in hepatic and portal vein thrombosis--possible evidence of an occult myeloproliferative state. Q J Med 1990; 76:981.
- Acharya J, Westwood NB, Sawyer BM, et al. Identification of latent myeloproliferative disease in patients with Budd-Chiari syndrome using X-chromosome inactivation patterns and in vitro erythroid colony formation. Eur J Haematol 1995; 55:315.
- De Stefano V, Teofili L, Leone G, Michiels JJ. Spontaneous erythroid colony formation as the clue to an underlying myeloproliferative disorder in patients with Budd-Chiari syndrome or portal vein thrombosis. Semin Thromb Hemost 1997; 23:411.
- Patel RK, Lea NC, Heneghan MA, et al. Prevalence of the activating JAK2 tyrosine kinase mutation V617F in the Budd-Chiari syndrome. Gastroenterology 2006; 130:2031.
- Qi X, Yang Z, Bai M, et al. Meta-analysis: the significance of screening for JAK2V617F mutation in Budd-Chiari syndrome and portal venous system thrombosis. Aliment Pharmacol Ther 2011; 33:1087.
- Smalberg JH, Arends LR, Valla DC, et al. Myeloproliferative neoplasms in Budd-Chiari syndrome and portal vein thrombosis: a meta-analysis. Blood 2012; 120:4921.
- Mishchenko E, Tadmor T, Schiff E, et al. Hypereosinophilia, JAK2V617F, and Budd-Chiari syndrome: who is responsible for what? Am J Hematol 2011; 86:223.
- Levy VG, Ruskone A, Baillou C, et al. Polycythemia and the Budd-Chiari syndrome: study of serum erythropoietin and bone marrow erythroid progenitors. Hepatology 1985; 5:858.
- Valla D, Le MG, Poynard T, et al. Risk of hepatic vein thrombosis in relation to recent use of oral contraceptives. A case-control study. Gastroenterology 1986; 90:807.
- Lewis JH, Tice HL, Zimmerman HJ. Budd-Chiari syndrome associated with oral contraceptive steroids. Review of treatment of 47 cases. Dig Dis Sci 1983; 28:673.
- Lalonde G, Théoret G, Daloze P, et al. Inferior vena cava stenosis and Budd--Chiari syndrome in a woman taking oral contraceptives. Gastroenterology 1982; 82:1452.
- Khuroo MS, Datta DV. Budd-Chiari syndrome following pregnancy. Report of 16 cases, with roentgenologic, hemodynamic and histologic studies of the hepatic outflow tract. Am J Med 1980; 68:113.
- Perarnau JM, Bacq Y. Hepatic vascular involvement related to pregnancy, oral contraceptives, and estrogen replacement therapy. Semin Liver Dis 2008; 28:315.
- Shetty S, Ghosh K. Thrombophilic dimension of Budd chiari syndrome and portal venous thrombosis--a concise review. Thromb Res 2011; 127:505.
- Fickert P, Ramschak H, Kenner L, et al. Acute Budd-Chiari syndrome with fulminant hepatic failure in a pregnant woman with factor V Leiden mutation. Gastroenterology 1996; 111:1670.
- Price DT, Ridker PM. Factor V Leiden mutation and the risks for thromboembolic disease: a clinical perspective. Ann Intern Med 1997; 127:895.
- Mahmoud AE, Elias E, Beauchamp N, Wilde JT. Prevalence of the factor V Leiden mutation in hepatic and portal vein thrombosis. Gut 1997; 40:798.
- Hoffman R, Nimer A, Lanir N, et al. Budd-Chiari syndrome associated with factor V leiden mutation: a report of 6 patients. Liver Transpl Surg 1999; 5:96.
- Qi X, Ren W, De Stefano V, Fan D. Associations of coagulation factor V Leiden and prothrombin G20210A mutations with Budd-Chiari syndrome and portal vein thrombosis: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2014; 12:1801.
- Laposata M. The prothrombin G20210A mutation: a new high-prevalence congenital risk factor for thrombosis. Gastroenterology 1999; 116:213.
- Saca LF, Szer IS, Henar E, et al. Budd-Chiari syndrome associated with antiphospholipid antibodies in a child: report of a case and review of the literature. J Rheumatol 1994; 21:545.
- Mackworth-Young CG, Melia WM, Harris EN, et al. The Budd-Chiari syndrome. Possible pathogenetic role of anti-phospholipid antibodies. J Hepatol 1986; 3:83.
- Van Steenbergen W, Beyls J, Vermylen J, et al. 'Lupus' anticoagulant and thrombosis of the hepatic veins (Budd-Chiari syndrome). Report of three patients and review of the literature. J Hepatol 1986; 3:87.
- Pomeroy C, Knodell RG, Swaim WR, et al. Budd-Chiari syndrome in a patient with the lupus anticoagulant. Gastroenterology 1984; 86:158.
- Espinosa G, Font J, García-Pagan JC, et al. Budd-Chiari syndrome secondary to antiphospholipid syndrome: clinical and immunologic characteristics of 43 patients. Medicine (Baltimore) 2001; 80:345.
- Das M, Carroll SF. Antithrombin III deficiency: an etiology of Budd-Chiari syndrome. Surgery 1985; 97:242.
- McClure S, Dincsoy HP, Glueck H. Budd-Chiari Syndrome and antithrombin III deficiency. Am J Clin Pathol 1982; 78:236.
- Sugano S, Suzuki T, Makino H, et al. Budd-Chiari syndrome attributed to protein C deficiency. Am J Gastroenterol 1996; 91:777.
- Majluf-Cruz A, Hurtado Monroy R, Sansores García L, Labardini-Méndez J. The incidence of protein C deficiency in thrombosis-related portal hypertension. Am J Gastroenterol 1996; 91:976.
- Bourlière M, Le Treut YP, Arnoux D, et al. Acute Budd-Chiari syndrome with hepatic failure and obstruction of the inferior vena cava as presenting manifestations of hereditary protein C deficiency. Gut 1990; 31:949.
- Valla D, Dhumeaux D, Babany G, et al. Hepatic vein thrombosis in paroxysmal nocturnal hemoglobinuria. A spectrum from asymptomatic occlusion of hepatic venules to fatal Budd-Chiari syndrome. Gastroenterology 1987; 93:569.
- Janssen HL, Meinardi JR, Vleggaar FP, 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; 96:2364.
- Mohanty D, Shetty S, Ghosh K, et al. Hereditary thrombophilia as a cause of Budd-Chiari syndrome: a study from Western India. Hepatology 2001; 34:666.
- Qi X, De Stefano V, Wang J, et al. Prevalence of inherited antithrombin, protein C, and protein S deficiencies in portal vein system thrombosis and Budd-Chiari syndrome: a systematic review and meta-analysis of observational studies. J Gastroenterol Hepatol 2013; 28:432.
- Deltenre P, Denninger MH, Hillaire S, et al. Factor V Leiden related Budd-Chiari syndrome. Gut 2001; 48:264.
- Denninger MH, Chaït Y, Casadevall N, et al. Cause of portal or hepatic venous thrombosis in adults: the role of multiple concurrent factors. Hepatology 2000; 31:587.
- Schafer AI. Hypercoagulable states: molecular genetics to clinical practice. Lancet 1994; 344:1739.
- Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996; 88:3698.
- Chamouard P, Pencreach E, Maloisel F, et al. Frequent factor II G20210A mutation in idiopathic portal vein thrombosis. Gastroenterology 1999; 116:144.
- Margaglione M, Brancaccio V, Giuliani N, et al. Increased risk for venous thrombosis in carriers of the prothrombin G-->A20210 gene variant. Ann Intern Med 1998; 129:89.
- Meijers JC, Tekelenburg WL, Bouma BN, et al. High levels of coagulation factor XI as a risk factor for venous thrombosis. N Engl J Med 2000; 342:696.
- Hoekstra J, Guimarães AH, Leebeek FW, et al. Impaired fibrinolysis as a risk factor for Budd-Chiari syndrome. Blood 2010; 115:388.
- Bayraktar Y, Balkanci F, Bayraktar M, Calguneri M. Budd-Chiari syndrome: a common complication of Behçet's disease. Am J Gastroenterol 1997; 92:858.
- Rector WG Jr, Xu YH, Goldstein L, et al. Membranous obstruction of the inferior vena cava in the United States. Medicine (Baltimore) 1985; 64:134.
- Simson IW. Membranous obstruction of the inferior vena cava and hepatocellular carcinoma in South Africa. Gastroenterology 1982; 82:171.
- Wang ZG. Management of Budd-Chiari syndrome: experience from 430 cases. Asian J Surg 1996; 19:23.
- Sevenet F, Deramond H, Hadengue A, et al. Membranous obstruction of the inferior vena cava associated with a myeloproliferative disorder: a clue to membrane formation? Gastroenterology 1989; 97:1019.
- Gwon D 2nd, Ko GY, Yoon HK, et al. Hepatocellular carcinoma associated with membranous obstruction of the inferior vena cava: incidence, characteristics, and risk factors and clinical efficacy of TACE. Radiology 2010; 254:617.
- Lu CL, Chou YH, Hwang SJ, et al. Membranous obstruction of inferior vena cava in Taiwan. J Gastroenterol Hepatol 1995; 10:287.
- Matsui S, Ichida T, Watanabe M, et al. Clinical features and etiology of hepatocellular carcinoma arising in patients with membranous obstruction of the inferior vena cava: in reference to hepatitis viral infection. J Gastroenterol Hepatol 2000; 15:1205.
- Valla D, Hadengue A, el Younsi M, et al. Hepatic venous outflow block caused by short-length hepatic vein stenoses. Hepatology 1997; 25:814.
- Young ID, Clark RN, Manley PN, et al. Response to steroids in Budd-Chiari syndrome caused by idiopathic granulomatous venulitis. Gastroenterology 1988; 94:503.
- Hernández-Guerra M, López E, Bellot P, et al. Systemic hemodynamics, vasoactive systems, and plasma volume in patients with severe Budd-Chiari syndrome. Hepatology 2006; 43:27.