Budd-Chiari syndrome

Budd-Chiari syndrome (BCS) is a rare condition characterized by hepatic vein obstruction that manifests with hepatomegaly, ascites, and abdominal discomfort. BCS is most commonly caused by thrombotic occlusion secondary to a chronic myeloproliferative neoplasm (e.g., polycythemia vera). Blood flow obstruction causes liver congestion and subsequent liver cell damage. If left untreated, patients may develop liver failure. Diagnosis is confirmed based on cross-sectional imaging (e.g., Doppler ultrasound). Management should be specialist-guided and include a strategy for restoring hepatic venous outflow with anticoagulation with or without invasive therapy (e.g., balloon angioplasty, or TIPS). Liver transplant should be considered if other treatments are unsuccessful. Additionally, underlying causes and complications (e.g., portal hypertension, variceal bleeding) should be managed.

BCS is characterized by hepatic vein obstruction, which is idiopathic in approx. 20% of cases or occurs secondary to: ^[1]

• Conditions associated with hypercoagulability (most common) ^[1][2]
  • Myeloproliferative neoplasms, e.g.:
    • Polycythemia vera (most common cause)
    • Essential thrombocythemia
  • Antiphospholipid syndrome
  • Paroxysmal nocturnal hemoglobinuria
  • Paraneoplastic thrombocytosis
  • Pregnancy and postpartum period
  • Inherited clotting disorders (e.g., factor V Leiden thrombophilia)
  • Chronic inflammatory diseases (e.g., Behcet disease)
  • Adverse effect of medication (e.g., hormonal contraception)
• Invasion or compression of the hepatic veins
  • Hepatocellular carcinoma (HCC)
  • Renal cell carcinoma
  • Chronic infections (e.g., amebiasis, aspergillosis, syphilis, tuberculosis)
  • Hepatic lesions

• Obstruction (e.g., due to thrombosis or compression) of hepatic veins → ↓ blood outflow → hepatic venous congestion → increased sinusoidal pressure, cellular hypoxia, centrilobular necrosis → congestive hepatopathy
• May develop into “nutmeg liver”: Because of ischemia and fatty degeneration, the tissue appears speckled with dark spots.
• Clinical symptoms depend on the extent of hepatic injury and portal hypertension.

References: ^[3]

• Abdominal pain
• Tender hepatomegaly
• Ascites and abdominal distention
• Jaundice
• Signs of increased perfusion of portocaval anastomoses (e.g., esophageal varices, or caput medusae)
• In severe cases: ankle edema, splenomegaly, and renal impairment

In contrast to congestive heart failure, which can also cause hepatic congestion, Budd-Chiari syndrome does not lead to jugular venous distension.

References: ^[4]

General principles ^[5][6]

Consider BCS in all patients with unexplained acute liver failure or chronic liver disease. ^[5]

• Diagnosis is confirmed by hepatic venous flow obstruction on imaging studies.
• Hepatic venography and liver biopsy are not usually required for diagnostic confirmation.
• Further studies are needed to evaluate for underlying causes, e.g., thrombophilia.
• Consult hepatology and/or hematology as needed in cases of diagnostic uncertainty.

BCS presentations are highly variable (i.e., acute, chronic, or acute-on-chronic), and clinical and laboratory findings are nonspecific. ^[1][6]

Imaging studies ^[5][6]

• Doppler ultrasound ^[5]
  • Obtain for all patients with suspected BCS (preferred initial test).
  • Findings of hepatic venous obstruction include: ^[5][6]
    • Presence of a thrombus
    • Nonvisible hepatic vein ^[6]
    • Collateral veins
    • Enlarged caudate vein diameter (> 3 mm)
    • Caudate lobe hypertrophy
  • Additional findings may include adenomas, nodular hyperplasia, or signs of HCC.
• CT with contrast or MRI scan is indicated for: ^[5]
  • Further characterization of lesions, including:
    • Thrombus on Doppler ultrasound ^[5]
    • Indeterminate hepatic nodules ^[6]
  • Inconclusive Doppler ultrasound in patients with high clinical suspicion ^[5]
  • Therapeutic assessment to determine response to anticoagulation therapy

Laboratory studies ^[5][6]

• Liver disease workup (findings are nonspecific)
  • Blood tests ^[6]
    • Elevated transaminases ^[1]
    • ↑ Bilirubin
    • ↓ Albumin and ↓ total protein
    • ↑ Prothrombin time (↑ INR) in advanced cases
    • Hyponatremia
  • Ascites fluid analysis ^[7][8]
    • High SAAG ascites
    • ↑ Protein levels > 2.5 g/dL in early BCS (may be low in later stages of the disease) ^[8]
• Thrombophilia workup: for all patients with confirmed BCS ^[6]
  • Consult hematology.
  • Obtain workup for hereditary thrombophilia and acquired thrombophilia (see “Etiology” for most common causes).
  • Additional factors should be investigated even if a single causal factor is identified.

General principles ^[1][5]

• Restoration of the hepatic venous outflow (e.g., using anticoagulation or invasive methods)
• Management of the underlying cause (e.g., thrombophilia)
• Management of complications (e.g., portal hypertension; , variceal bleeding, ascites, acute liver failure)
• Consult hepatology, hematology, and other specialties as needed.

A stepwise treatment approach from least invasive (e.g., anticoagulation) to most invasive (e.g., liver transplant) is usually recommended. ^[5]

Noninvasive therapy ^[5][6]

• Long-term anticoagulant therapy: initial treatment of choice ^[5][6]
  • Recommended for all patients regardless of the underlying cause ^[6]
  • Gastroesophageal varices are not a contraindication for anticoagulant use. ^[5]
  • Recommended regimen: initial therapy with LMWH, followed by VKA ^[6]
• Treatment of portal hypertension (as indicated for patients with cirrhosis): e.g., diuretics, nonselective beta blockers for prophylaxis of variceal bleeding ^[1][5]

Invasive therapy ^[5][6]

Invasive therapy is usually indicated if noninvasive approaches have been unsuccessful. ^[5][6]

• Recanalization of obstructed vessels, including:
  • Balloon angioplasty ± stenting of the hepatic vein: most effective for short-segment hepatic vein obstruction
  • Localized thrombolysis (low success rate) : may be useful for acute stent or TIPS thrombosis ^[5]
• Shunts: to decompress the hepatic sinusoids: i.e., TIPS, direct intrahepatic portosystemic shunts , or surgical portosystemic shunts ^[6]
• Liver transplant
  • For patients with liver failure or if less invasive approaches are unsuccessful
  • Curative for selected prothrombotic diseases, e.g., protein C deficiency or protein S deficiency ^[1]

• Portal hypertension
• Acute liver failure
• Cirrhosis
• Hepatocellular carcinoma (HCC) ^[9]

We list the most important complications. The selection is not exhaustive.