Budd–Chiari Syndrome in Pediatrics

Definition

• Thrombotic or nonthrombotic postsinusoidal hepatic venous outflow obstruction.
• Occurs anywhere from small hepatic venules to the right atrium.
• Excludes cardiac, pericardial, or intrinsic sinusoidal disorders.

Epidemiology

• Accounts for approximately 2–5% of liver-failure cases in children and adults.
• Only about 5% of all BCS diagnoses occur in patients ≤12 years old.
• Estimated pediatric incidence: <0.5 per million children per year.

Pathogenesis

1. Primary (Venous)

• Acquired thrombophilias
  • Myeloproliferative disorders (30–50% of cases), often with JAK2 V617F mutation.
  • Antiphospholipid syndrome, paroxysmal nocturnal hemoglobinuria, nephrotic syndrome.
  • Hormonal factors: oral contraceptives, pregnancy.
• Inherited thrombophilias
  • Factor V Leiden mutation
  • Prothrombin G20210A mutation
  • Protein C, protein S, and antithrombin-III deficiencies

2. Secondary (Extravascular)

• Compression or invasion of hepatic veins/IVC by tumors (e.g., hepatoblastoma), cysts, abscesses, or vascular malformations.

Clinical Presentation

Temporal Patterns

• Fulminant (<2 weeks; 5%): RUQ pain, ascites, jaundice, encephalopathy.
• Acute non-fulminant (weeks; 20%): Ascites and pain without encephalopathy.
• Subacute/chronic (insidious; 60%): Progressive ascites, hepatomegaly, portal hypertension.
• Asymptomatic in ~15% at diagnosis.

Signs & Symptoms

• Right upper quadrant pain and hepatomegaly.
• Rapidly developing ascites and abdominal distention.
• Portal hypertension sequelae: splenomegaly, variceal bleeding.
• Variable jaundice; renal dysfunction in severe cases.

Laboratory Findings

• Elevated AST and ALT.
• Hyperbilirubinemia (cholestatic or mixed pattern).
• Prolonged INR and low albumin.
• Serum-ascites albumin gradient ≥1.1 g/dL.
• Thrombocytopenia or leukopenia from hypersplenism.

Diagnosis

Imaging

• Doppler Ultrasound: First-line—absent or reversed hepatic vein flow; caudate-lobe hypertrophy; collateral circulation.
• Triphasic CT & MRI: Segmental enhancement defects; thrombus characterization; collateral pathways.
• Venography: Direct or transjugular retrograde study for equivocal cases.

Thrombophilia Evaluation

• JAK2 V617F mutation analysis.
• Antiphospholipid antibody panel.
• Protein C, protein S, antithrombin-III levels.
• Factor V Leiden and prothrombin gene testing.
• Flow cytometry for paroxysmal nocturnal hemoglobinuria.

Management

1. Supportive Care

• Sodium restriction and diuretics for ascites.
• Therapeutic paracentesis with albumin replacement.
• Variceal screening and prophylaxis (endoscopic band ligation).
• Correction of coagulopathy and hepatic encephalopathy.

2. Anticoagulation

• Lifelong anticoagulation unless contraindicated.
• LMWH transitioning to warfarin (target INR 2–3).
• Consider direct oral anticoagulants in older adolescents.

3. Recanalization & Shunt Procedures

• Angioplasty ± stenting for short-segment venous occlusions.
• Transjugular intrahepatic portosystemic shunt (TIPS) for refractory ascites or variceal bleeding; bridge to transplant if needed.

4. Liver Transplantation

• Indications: fulminant hepatic failure unresponsive to intervention; decompensated cirrhosis; persistent portal hypertension complications.
• Pediatric 5-year post-transplant survival >80%.

5. Treat Underlying Etiology

• Cytoreductive therapy for myeloproliferative disorders (e.g., hydroxyurea).
• Immunomodulation for antiphospholipid syndrome or PNH (e.g., eculizumab).

Prognosis

• With anticoagulation and interventional therapy, 5-year transplant-free survival is 60–70%.
• Poor prognostic factors: fulminant onset, renal dysfunction, high bilirubin, low albumin, failed recanalization.

Key Points

• Suspect BCS in any child with unexplained ascites, hepatomegaly, or portal hypertension.
• Doppler ultrasound is diagnostic in most cases; advanced imaging guides intervention.
• Stepwise management—anticoagulation, recanalization, TIPS, transplant—optimizes outcomes.
• Multidisciplinary care is essential, involving hepatology, radiology, hematology, and transplant surgery.