What is Budd Chiari syndrome?

Budd-Chiari Syndrome: Definition, Diagnosis, and Management

Budd-Chiari syndrome is a rare condition characterized by obstruction of hepatic venous outflow that can occur anywhere from small hepatic venules up to the entrance of the inferior vena cava into the right atrium, excluding cardiac disease, pericardial disease, or sinusoidal obstruction syndrome. 1

Etiology

Budd-Chiari syndrome is primarily caused by:

• Myeloproliferative neoplasms (40-50% of cases) - most common cause in Western countries, often associated with JAK2V617F mutation 1
• Thrombophilic disorders:
  • Factor V Leiden mutation (25% of cases)
  • Prothrombin G20210A gene variant
  • Antiphospholipid syndrome
  • Paroxysmal nocturnal hemoglobinuria
  • Other inherited or acquired thrombophilias 1
• Malignancy-associated hypercoagulability - important to rule out before considering transplantation 2

Clinical Presentation

Budd-Chiari syndrome can present with:

• Abdominal pain
• Hepatomegaly (often striking)
• Ascites
• Jaundice
• Various degrees of liver dysfunction 2, 1

The presentation may be acute, subacute, or chronic. In most cases, chronic indolent presentations are more common than acute ones 3. However, in severe cases, Budd-Chiari syndrome can progress to acute liver failure, which is associated with higher mortality (approximately 60%) 4.

Diagnosis

A high index of suspicion is required, particularly in patients with risk factors for thrombosis 3. The diagnostic approach includes:

1. Doppler ultrasound - first-line diagnostic study with sensitivity >75% 1
2. Advanced imaging - if diagnosis remains uncertain:
   • MRI or CT evaluation
   • Direct venography 1
3. Liver biopsy - when imaging doesn't detect large vein obstruction; shows severe pericentral necrosis in acute cases 1, 4
4. Thrombophilia screening:
   • Protein S, protein C, and antithrombin levels
   • Factor V Leiden mutation
   • Prothrombin G20210A gene variant
   • Antiphospholipid antibodies (repeat after 12 weeks if positive)
   • JAK2V617F mutation testing 1

Treatment

Treatment follows a stepwise approach based on disease severity:

1. Immediate anticoagulation:

   • Start with low molecular weight heparin (LMWH) for 5-7 days
   • Follow with oral vitamin K antagonists (target INR 2-3)
   • Continue anticoagulation indefinitely, especially in patients with myeloproliferative disorders 1

2. Treatment of underlying cause:

   • Management of myeloproliferative disorders
   • Address other prothrombotic conditions 1

3. Interventional procedures (for those who fail medical management):

   • Angioplasty and stenting (for eligible patients)
   • Transjugular intrahepatic portosystemic shunt (TIPS) 1, 5

4. Liver transplantation for:

   • Failed TIPS
   • Fulminant hepatic failure
   • Advanced cirrhosis 2, 1

Prognosis

With advances in diagnosis and treatment, prognosis has significantly improved:

• 1-year survival rate: 87%
• 2-year survival rate: 82% 1
• Modern treatment algorithms have dramatically improved outcomes compared to historical data 5

Special Considerations

• Pregnancy: LMWH is the anticoagulant of choice as vitamin K antagonists are contraindicated due to risk of fetal hemorrhage and teratogenicity 1

• Malignancy screening: Essential before liver transplantation as malignancy-associated hypercoagulability is a potential cause 2

• Chronic disease progression: Untreated Budd-Chiari syndrome can lead to liver cirrhosis with complications like refractory ascites 6

Pitfalls to Avoid

• Delayed diagnosis: Maintain a low threshold for suspicion in patients with risk factors for thrombosis
• Incomplete thrombophilia workup: Always perform comprehensive screening for underlying causes
• Inadequate anticoagulation: This is the cornerstone of treatment and should be initiated promptly
• Missing multiple risk factors: Many patients have more than one underlying prothrombotic condition 7