What is Budd-Chiari syndrome in an asymptomatic adult with mildly elevated red blood cell parameters and potential polycythemia vera?

What is Budd-Chiari Syndrome?

Budd-Chiari syndrome is a rare but potentially life-threatening disorder caused by obstruction of hepatic venous outflow, occurring anywhere from the small hepatic venules to the entrance of the inferior vena cava into the right atrium. 1

Pathophysiology

The venous obstruction in Budd-Chiari syndrome leads to a cascade of hepatic injury 1:

• Sinusoidal congestion develops as blood cannot drain properly from the liver 1
• Hepatic ischemia occurs due to impaired blood flow 1
• Hepatocellular necrosis results from the ischemic injury 1
• Progressive fibrosis can develop, leading to centrilobular fibrosis, nodular regenerative hyperplasia, and potentially cirrhosis 1

The syndrome represents post-sinusoidal (post-hepatic) portal hypertension, which distinguishes it from cirrhotic portal hypertension that is primarily sinusoidal 1. Importantly, the liver parenchyma may initially remain relatively preserved despite severe portal hypertension 1.

Clinical Presentation

The clinical manifestations are highly variable, ranging from completely asymptomatic cases to fulminant hepatic failure 1. This heterogeneity makes diagnosis challenging and requires a high index of suspicion 2.

Common presenting features include 1:

• Ascites (present in 83% of patients at diagnosis)
• Hepatomegaly (present in 67% of patients)
• Abdominal pain
• Intractable ascites in more severe cases
• Rapidly progressive liver failure in fulminant presentations

Up to 20% of cases are asymptomatic, indicating chronic onset with formation of large hepatic vein collaterals 3.

Underlying Causes and Risk Factors

Myeloproliferative Neoplasms

Myeloproliferative neoplasms are the most common cause, accounting for approximately 49% of Budd-Chiari syndrome cases 1. This is particularly relevant to your context of potential polycythemia vera:

• Polycythemia vera is a major causative disorder 1
• Essential thrombocytosis also contributes 1
• JAK2V617F mutation testing and bone marrow histology are crucial diagnostic steps 1
• In young women with polycythemia vera, Budd-Chiari syndrome can represent an aggressive form of myeloproliferative disorder requiring immediate recognition and multidisciplinary management 4

Inherited Thrombophilias

Multiple inherited coagulation disorders increase risk 1:

• Factor V Leiden mutation
• Protein C deficiency
• Protein S deficiency
• Antithrombin deficiency
• Prothrombin G20210A gene variant

Other Risk Factors

Additional causes include 1:

• Malignancies
• Paroxysmal nocturnal hemoglobinuria
• Antiphospholipid antibodies
• Intra-abdominal inflammatory conditions

In up to 25% of patients, no underlying disorder is identified 5.

Diagnostic Approach

Doppler ultrasound is the first-line and definitive radiographic study, with diagnostic sensitivity exceeding 75% when performed by an experienced operator 6. The American College of Radiology confirms that Doppler ultrasound by an experienced operator is sufficient to establish or rule out Budd-Chiari syndrome in most patients 6.

Distinctive Ultrasound Features 6:

• Absence of visualization or tortuosity of hepatic veins
• Intrahepatic or subcapsular hepatic venous collaterals (found in >80% of cases)
• Caudate lobe enlargement

Second-Line Imaging

• MRI with hepato-specific contrast agents is useful for detecting hypervascular liver nodules prior to treatment 6
• MRI is less effective than ultrasound for demonstrating intrahepatic collaterals but more accurate than venacavography for characterizing solid endoluminal material 6
• CT scan has significant limitations, including high false positive rates (~50%), radiation exposure, and potential renal toxicity 6

Third-Line Investigation

Direct X-ray venography (hepatic venography) is needed for establishing diagnosis in difficult cases and is essential for precise delineation of obstructive lesions before planning treatment 6.

Laboratory Workup

Comprehensive thrombophilia screening is essential 1:

• Protein S, protein C, and antithrombin levels
• Factor V Leiden mutation
• Prothrombin G20210A gene variant
• Antiphospholipid antibodies
• JAK2V617F mutation testing (critical for myeloproliferative neoplasms)
• Calreticulin mutation screening
• Bone marrow histology when myeloproliferative disorder suspected

Management Principles

All patients with Budd-Chiari syndrome must be managed in specialized centers with expertise in hepatology, interventional radiology, and access to liver transplantation 7.

Immediate Anticoagulation

Anticoagulation should be initiated as soon as possible and continued indefinitely to reduce the risk of clot extension and new thrombotic episodes 7. The protocol includes 7:

• Low molecular weight heparin (LMWH) for at least 5-7 days initially
• Transition to oral vitamin K antagonists (VKA) with target INR 2-3
• Lifelong anticoagulation unless major contraindications exist

Treatment Algorithm

The European Association for the Study of the Liver recommends a sequential, stepwise approach 7:

1. Immediate anticoagulation for all patients
2. Angioplasty/stenting for focal stenoses (effective in 60% of IVC obstruction cases and 25-30% of hepatic vein obstruction cases)
3. TIPS (transjugular intrahepatic portosystemic shunt) for refractory cases or when angioplasty fails, with symptom resolution exceeding 70% and 5-year survival rates exceeding 70%
4. Liver transplantation as salvage therapy for patients who fail all other options

Special Considerations

• Treatment of underlying myeloproliferative disorders should be initiated concurrently with anticoagulation 7
• Management of portal hypertension complications (ascites and varices) follows the same guidelines as for cirrhosis 7
• Regular Doppler ultrasound monitoring every 6 months is recommended to detect thrombosis or dysfunction after treatment 6

Prognosis

The clinical course ranges from insidious progression with ascites to hyperacute presentation with liver failure 8. With appropriate management in specialized centers, 5-year survival rates can exceed 70% following TIPS placement 7. However, patients presenting with fulminant hepatic failure require urgent consideration for TIPS and potential liver transplantation 7.