Budd-Chiari syndrome is associated with a wide range of etiologies. On the basis of underlying cause Budd- Chairi syndrome can be primary (75%) caused by thrombosis of the hepatic vein or secondary (25%) caused by invasion/compression of the hepatic vein by an outside structure such as a tumor, abscess or cysts. Causes include myeloproliferative disorders, malignancy, paroxysmal nocturnal hemoglobinuria, antiphospholipid syndrome, factor V leiden mutation, infections and benign liver lesions, oral contraceptives and pregnancy, hypercoagulable states, Behçet’s syndrome, membranous webs.

• Budd-Chiari syndrome is associated with a wide range of etiologies.^[1][2][3][4]
• On the basis of underlying cause Budd- Chairi can be:
  • Primary (75%): thrombosis of the hepatic vein
  • Secondary (25%): invasion/compression of the hepatic vein by an outside structure like(e.g. a tumor, abscess or cysts)

Causes include:

• Myeloproliferative disorders:
  • Myeloproliferative and other hemotologic abnormalities are one of the most common causes of Budd Chiari Syndrome.
  • V617F mutation in Janus tyrosine kinase-2 (JAK2) is found in 80% of patients with polycythemia vera and 50% of patients with essential thrombocythemia or idiopathic myelofibrosis. Budd Chiari syndrome patients that test negative for this mutation should have bone marrow biopsy performed.
  • Other associated hematologic causes include:
    • Paroxysmal nocturnal hemoglobinuria
    • Antiphospholipid syndrome
    • factor V leiden mutation
    • prothrombin gene mutation
    • methylene tetrahydrofolate reductase gene mutation

• Malignancy
  • Malignancy is commonly associated with compression or invasion of vessels and hypercoagulable state.
  • Budd-Chiari is commonly associated with
    • hepatocellular carcinoma(associated with membranous obstruction of inferior vena cava)
    • adrenal gland or renal malignancy
    • right atrial sarcoma
    • pancreatic cancer
    • lung carcinoma
    • gastric carcinoma

• Infections and benign liver lesions
  • Cause extrinsic compression of inferior vena cava. May be associated with hypercoagulable state. These lesions include:
    • hepatic cysts and abscesses
    • hepatic adenoma
    • hepatic mucinous cystic neoplasm (cystadenoma)
    • syphilitic gumma
    • invasive aspergillosis
    • zygomycosis (mucormycosis)
    • aortic aneurysm

• Oral contraceptives and pregnancy
  • Hypercoagulable state in women using oral contraceptives (for more than two weeks), pregnant , or those who have delivered a child within the previous two months accounts for nearly 20 percent of cases of the Budd-Chiari syndrome

• Other hypercoagulable states

Hypercoagulable conditions associated with Budd-Chiari include:

• • G1691A factor V (Leiden) gene mutation associated with activated protein C resistance
  • G20210A factor II gene mutation
  • Antiphospholipid syndrome
  • Antithrombin deficiency
  • Protein C deficiency
  • Protein S deficiency
  • Paroxysmal nocturnal hemoglobinuria

• Behçet’s syndrome
  • Vasculitis in Behçet’s syndrome can predispose to thrombosis.
• Membranous webs are usually are found near the entrance of the right hepatic vein into the inferior vena cava, may be due to a congenital anomaly or a myeloproliferative disease.
• More common in patients from South Africa, India, and Asia. Potentially treatable cause of Budd-chiari.
• Miscellaneous:
  • Miscellaneous causes of the Budd-Chiari syndrome include:
    • Systemic lupus erythematosus
    • Mixed-connective tissue disease
    • Sjögren’s syndrome
    • Inflammatory bowel disease
    • Hypereosinophilic syndrome
    • Idiopathic granulomatous venulitis
    • Sarcoidosis
    • Protein-losing enteropathy
    • Minimal change disease
    • Neurofibromatosis
    • Alpha-1 antitrypsin deficiency
    • Trauma
• Idiopathic:
  • Upto 20 percent of cases of the Budd-Chiari syndrome are idiopathic.