A 45-year-old woman presents to the emergency department complaining of nausea and extreme abdominal pain on her right side. She notes that symptoms came on suddenly 2 days before. The patient works as a personal fitness trainer and exercises daily. She drinks an occasional glass of red wine and takes hydrochlorothiazide 25 mg/d for hypertension.
On physical examination, the patient has a low-grade fever and slight chill (Table). Her abdomen is soft, with shifting dullness consistent with an enlarged liver and moderate ascites. Tenderness and guarding over the right lower quadrant are noted. The spleen is palpable in the left upper quadrant, and bowel sounds are hyperactive. Costovertebral angle tenderness is absent. Neurologic and extremity examinations are normal.
Computed tomographic (CT) imaging of the abdomen shows hepatomegaly (16 cm) and moderate ascites suggestive of cirrhosis and end-stage liver disease. During the course of her visit, the patient’s symptoms worsen to include vomiting, right lower quadrant abdominal pain, dizziness, and diaphoresis.
The patient is immediately admitted to the intensive care unit and treated for sepsis. The following day, she develops fulminant liver failure. After transfer to a specialist center, the patient’s symptoms progress to shock, ascites, jaundice, acute kidney injury, acute respiratory failure, and metabolic acidosis.
Two days later, she undergoes further studies that include Doppler ultrasound, CT of the abdomen with contrast, CT-guided paracentesis, and echocardiogram. The diagnosis of Budd-Chiari syndrome (BCS) is made based on a combination of physical findings and ultrasound and CT evidence of hepatic vein occlusion. Liver biopsy reveals that the patient’s liver is 60% necrotic, with no evidence of inflammation or chronic liver disease.
Although most clinicians may not recognize BCS, understanding the trio of symptoms — abdominal pain, hepatomegaly, and ascites — can improve the likelihood of an accurate diagnosis and facilitate optimal treatment.
George Budd first described the clinical picture of BCS in 1845 and Hans Chiari described the underlying histopathology half a century later.1 A multifactorial disease process characterized by hepatic venous outflow obstruction, BCS occurs in approximately 1.4 million people in the United States.2,3 An underlying disorder can be identified in more than 80% of these patients.2
Causes of BCS include myeloproliferative syndromes (MPS), malignancy, infection, Behҫet syndrome, as well as miscellaneous other conditions and idiopathic causes. The American Association for the Study of Liver Diseases, therefore, recommends evaluating individuals with BCS for lesions or malignant tumors, thrombosis, and systemic diseases.4
BCS often is the initial presentation of an MPS, and approximately 50% of BCS cases may be due to an underlying MPS, such as essential thrombocytopenia, primary myelofibrosis, agnogenic myeloid metaplasia, and the most common MPS, polycythemia vera.2 In one study, bone marrow biopsy showed that 78% of patients diagnosed with idiopathic BCS had a primary MPS.5
Malignancies are implicated in the etiology of BCS in nearly 10% of cases.6 Hepatocellular carcinoma is the most frequent malignancy, followed by malignancies of the adrenal gland, kidney, lung, pancreas, and stomach, as well as sarcomas of the right atrium, inferior vena cava, or hepatic veins.7 Invasion of vascular structures coupled with the hypercoagulable state associated with malignancy can result in venous thrombosis and/or obstruction.
Systemic diseases associated with BCS include autoimmune diseases (such as systemic lupus erythematosus), mixed connective tissue disease, and Sjögren syndrome. Inflammatory bowel disease, sarcoidosis, minimal change nephrotic syndrome, neurofibromatosis, trauma, torsion of the liver, and rare familial clusters also have been identified as being associated with BCS.
Infections and benign lesions account for another 10% of BCS cases.6 Women who are pregnant, use oral contraceptives, or are postpartum account for nearly 20% of BCS cases. Well-defined risk factors for thrombosis include factor V Leiden mutation, factor II gene mutation, antiphospholipid syndrome, antithrombin deficiency, protein C and S deficiencies, and paroxysmal nocturnal hemoglobinuria.7 There is no known underlying cause of BCS in up to 20% of cases.2