What are the risk factors and symptoms of Budd-Chiari syndrome?

Risk Factors and Symptoms of Budd-Chiari Syndrome

Budd-Chiari syndrome (BCS) is primarily caused by underlying prothrombotic disorders, with myeloproliferative neoplasms being the most common etiology, present in approximately 49% of patients. 1

Definition and Pathophysiology

Budd-Chiari syndrome is defined as obstruction of hepatic venous outflow that can be located anywhere from the small hepatic venules up to the entrance of the inferior vena cava (IVC) into the right atrium. This definition excludes hepatic outflow obstruction related to cardiac disease, pericardial disease, or sinusoidal obstruction syndrome. 2

The pathophysiological consequences include:

• Venous obstruction leading to sinusoidal congestion
• Hepatic ischemia
• Hepatocellular necrosis
• Potential progression to centrilobular fibrosis, nodular regenerative hyperplasia, and/or cirrhosis 2

Risk Factors

Prothrombotic Disorders

• Myeloproliferative neoplasms (MPNs): Most common cause (49% of cases), including polycythemia vera and essential thrombocytosis 1, 2
• Inherited thrombophilias:
  • Factor V Leiden mutation (accounts for 25% of cases) 2
  • Protein C deficiency 2
  • Protein S deficiency 2
  • Antithrombin deficiency 2
  • Prothrombin G20210A gene variant 2

Other Risk Factors

• Multiple risk factors: Up to 46% of patients have more than one prothrombotic risk factor 1
• Malignancies: Account for approximately 10% of cases through compression or direct invasion of hepatic veins or vena cava 2
• Paroxysmal nocturnal hemoglobinuria 2
• Antiphospholipid antibodies 2
• Intra-abdominal inflammatory conditions 2

Clinical Presentation and Symptoms

The clinical presentation of BCS is heterogeneous, ranging from asymptomatic to fulminant hepatic failure. 2

Common Symptoms and Signs

• Ascites: Present in 83% of patients at diagnosis 2
• Hepatomegaly: Present in 67% of patients 2
• Abdominal pain: Common presenting symptom 2, 3
• Intractable ascites: Particularly common in chronic forms 2
• Rapidly progressive liver failure: In acute presentations 2

Disease Course Patterns

• Asymptomatic presentation: Often associated with large hepatic venous collaterals 2
• Acute presentation: Rapid onset with severe symptoms and potential fulminant hepatic failure 2
• Chronic presentation: More common than acute presentations, with indolent symptoms 4
• Fulminant presentation: Rare but life-threatening 2

Diagnostic Approach

Diagnosis requires a high index of suspicion, especially in patients with unexplained portal hypertension or risk factors for thrombosis. 4, 5

Imaging Studies

• Doppler ultrasound: First-line investigation with diagnostic sensitivity >75% 2
• MRI/CT: Used for diagnostic confirmation when ultrasound is inconclusive 2
• Venography: Recommended when diagnosis remains uncertain or for characterizing anatomy prior to treatment 2
• Liver biopsy: May be used if imaging fails to demonstrate obstruction of large veins 2

Laboratory Evaluation

• Thrombophilia screening: Should include protein S, protein C, antithrombin levels, Factor V Leiden mutation, prothrombin G20210A gene variant, and antiphospholipid antibodies 2
• Testing for myeloproliferative neoplasms: JAK2V617F mutation testing is essential, even in patients with normal blood counts 2
• Calreticulin mutation screening: Should be performed in JAK2V617F-negative patients 2
• Bone marrow histology: Should be considered if both JAK2V617F and calreticulin mutations are negative 2

Management Considerations

Treatment of BCS follows a stepwise approach based on disease severity and response to therapy. 6, 2

Medical Management

• Anticoagulation: Should be started as soon as possible and continued indefinitely to reduce risk of clot extension and new thrombotic episodes 2
• Treatment of underlying conditions: Particularly important for myeloproliferative disorders 2

Invasive Interventions

• Angioplasty/stenting: For accessible venous stenoses 2
• Transjugular intrahepatic portosystemic shunts (TIPS): For patients not responding to medical therapy or angioplasty 2
• Liver transplantation: For patients with progressive end-stage liver disease or fulminant presentation 2

Prognosis

With contemporary management using a stepwise approach, survival rates are approximately 87% at 1 year and 82% at 2 years. 1, 6

Special Considerations

• Recurrence risk: Long-term monitoring is essential as disease can recur 3
• Progression of underlying disorders: Particularly myeloproliferative neoplasms 3
• Post-transplant complications: Including potential development of lymphoma in transplant patients 3