• Information
  1. Characteristics
  2. Etiology (Table 1)
  3. Pathophysiology
  4. Diagnosis
  5. Treatment

A. Characteristics

1. Group of disorders of hepatic venous outflow obstruction
2. Outflow obstruction may occur at any of several levels
   1. Hepatic venules
   2. Large hepatic veins
   3. Inferior vena cava (IVC)
   4. Right atrium
3. Obstruction leads to portal hypertension and eventually ascites
4. Hepatocyte necrosis can occur
5. Presentation can be fulminant, acute, subacute or chronic
   1. Nearly all patients have abdominal pain, hepatomegaly, ascites
   2. Nausea, vomiting, mild jaundice in fulminant and acute forms
   3. Splenomegaly and esophageal varices often present in chronic forms
   4. Pedel edema may be prominent with IVC occlusion
6. Relief of obstruction improves liver function

B. Etiology (Table 1, Ref [1])

1. Many predisposing factors, particularly coagulopathies [2]
2. Hypercoagulable States (~75%)
   1. Both inherited and acquired conditions
   2. Inherited factor deficiency: antithrombin, protein C, protein S deficiency
   3. Abnormal coagulation proteins: Factor V Leiden, prothrombin mutation
3. Acquired Hypercoagulable States
   1. Myeloproliferative disorders (common)
   2. Paroxysmal nocturnal hemoglobinuria (PNH)
   3. Antiphospholipid syndrome (APLS)
   4. Cancer
   5. Pregnancy
   6. Oral contraceptives (OCP)
4. Myeloproliferative Disorders
   1. Involved in ~50% of Budd-Chiari Cases
   2. Polycythemia vera
   3. Essential thrombocythemia
5. Uncommon Causes
   1. Neoplastic invasion: hepatocellular, renal, adrenal carcinomas
   2. Aspergillosis infection (invasion)
   3. Inflammation: Behcet's Syndrome, inflammatory bowel disease
   4. Inferior vena caval webs
   5. Dacarbazine
6. Idiopathic

C. Pathophysiology

1. Blockade of hepatic venous outflow increases hepatic sinusoidal pressures
2. Portal hypertension (HTN) ensues and portal venous perfusion of liver is reduced
3. Reduced portal perfusion leads to stasis and can result in portal venous thrombosis
4. Hepatic Venous (Venular) Stasis Causes:
   1. Damage to adjacent hepatic parenchymal cells
   2. Release of free radicals and oxidative injury to hepatocytes
   3. Hepocyte necrosis in centrilobular regions occur
   4. Centrilobular fibrosis is followed by nodular regenerative hyperlasia
   5. Nodular regenerative hyperplasia with fibrosis is hepatic cirrhosis
5. Reduction of hepatic sinusoidal pressure can lead to improvement in liver function

D. Diagnosis

1. Serum Chemistries
   1. Asparate (AST, SGOT) and alanine (ALT, SGPT) aminotransferase elevations (up to 5X)
   2. Serum alkaline phosphatase and bilirubin also increase
   3. Serum albumin levels reduced dependent on loss of synthetic function
2. Ascites is transudative
   1. High serum-ascitic fluid level gradient
   2. Total protein level in ascitic fluid usually >2.5gm/dL
3. Doppler Ultrasound of Liver
   1. Primary modality for suspected BCS
   2. Sensitivity and specificity ~85%
4. Computerized tomography (CT) visualizes necrotic area of liver
5. Magnetic resonance imaging (MRI) is very accurate, particularly in IVC related disease
6. Cardiac echocardiography can be used to evaluate right atrial disease
7. Diagnosis confirmation is required: hepatic venography shows spiderweb pattern

E. Treatment

1. Both medical and invasive therapies are usually required
2. Medical Management
   1. Reduce further development of ascites - aldosterone blockers, diuretics
   2. Anticoagulation therapy to prevent extension of venous thrombosis
   3. Large volume paracentesis (with albumin infusions) useful in tense or refractory ascites
   4. Long term anticoagulation prevents recurrences
3. Relief of Hepatic Venous Outflow Obstruction
   1. Thromblytic therapy - mainly for acute BCS; urokinase or tissue plasminogen activator
   2. Angioplasty of localized segments of hepatic vein or IVC may be considered
   3. Transjugular intrahepatic portosystemic shunt (TIPSS) - good chronic therapy
   4. Peritoneovenous shunts placed surgically
4. Liver transplantation - good long term survival

References

1. Menon KVN, Shah V, Kamath PS. 2004. NEJM. 350(6):578
2. Chung RT, Iafrate AJ, Amrein PC, et al. 2006. NEJM. 354(20):2166 (Case Record)