How to diagnose hepatic vein thrombosis?

Diagnosis of Hepatic Vein Thrombosis

Doppler ultrasonography by an experienced examiner is the first-line diagnostic test for hepatic vein thrombosis, with MRI or CT scan as alternatives when experienced sonographers are unavailable. 1

Clinical Presentation

Hepatic vein thrombosis (Budd-Chiari syndrome) presents with a spectrum of symptoms ranging from asymptomatic to fulminant hepatic failure:

• Common clinical manifestations:

  • Ascites (83% of cases) 1
  • Hepatomegaly (67% of cases) 1
  • Abdominal pain (61% of cases) 1
  • Esophageal varices (58% of cases) 1
  • Gastrointestinal bleeding (5% of cases) 1
  • Extensive subcutaneous veins on the trunk (specific for IVC obstruction) 1

• Clinical suspicion should be raised when:

  • Acute or chronic illness with upper abdominal pain, ascites, or liver enlargement
  • Liver disease in a patient with known thrombotic risk factors
  • Liver disease with extensive subcutaneous veins of the trunk
  • Unexplained liver disease after excluding common causes 1

Diagnostic Algorithm

1. First-line imaging: Doppler ultrasonography

   • Specific findings on color Doppler and pulse Doppler:
     • Large hepatic vein with absent, reversed, or turbulent flow
     • Large intrahepatic/subcapsular collaterals connecting hepatic veins or diaphragmatic/intercostal veins
     • Spider-web appearance near hepatic vein ostia with absence of normal hepatic vein
     • Absent/flat hepatic vein waveform without fluttering
     • Hyperechoic cord replacing normal vein 1

2. Second-line imaging (if Doppler is inconclusive or unavailable):

   • MRI with gadolinium enhancement
   • CT with contrast enhancement
   • These can visualize obstructed hepatic veins, IVC, intrahepatic collaterals, and spider-web patterns 1

3. X-ray venography (if diagnosis remains uncertain):

   • Considered the gold standard
   • Specific patterns include:
     • Fine "spider-web" network without filling of venous radicals
     • Coarse network of collateral veins arching outward from catheter tip
     • Patent vein upstream from a stricture 1

4. Liver biopsy:

   • Only when obstructed hepatic venous outflow tract has not been demonstrated with non-invasive imaging
   • Findings include congestion, liver cell loss, and fibrosis in the centrilobular area
   • Only means to diagnose rare forms of BCS involving small hepatic veins with patent large veins 1

Additional Diagnostic Workup

Once hepatic vein thrombosis is confirmed, investigate for underlying prothrombotic factors:

• Thrombophilia screening:

  • Protein S, protein C, and antithrombin levels
  • Factor V Leiden mutation
  • Prothrombin G20210A gene variant
  • Anti-phospholipid antibodies (repeat after 12 weeks if positive) 1

• Myeloproliferative neoplasm testing:

  • JAK2V617F mutation (present in 20-40% of patients with splanchnic vein thrombosis) 1
  • If JAK2V617F negative, test for calreticulin mutation
  • Consider bone marrow histology if both are negative 1

• Other tests:

  • Paroxysmal nocturnal hemoglobinuria (PNH) screening
  • Autoimmune disorder evaluation
  • Assessment for local factors (intra-abdominal inflammatory conditions, malignancies) 1

• Laboratory testing:

  • Complete blood count with platelet count and differential
  • PT, aPTT
  • Basic metabolic profile
  • Hepatic profile
  • Serum lactate 1

Diagnostic Pitfalls and Caveats

1. Imaging interpretation challenges:

   • Caudate lobe hypertrophy (found in 75% of patients) can cause narrowing of the IVC at its intrahepatic portion, mimicking obstruction 1
   • Macroregenerative nodules enhancing at arterial phase should not be mistaken for hepatocellular carcinoma without additional supporting evidence 1

2. Liver biopsy limitations:

   • Considerable sample variation
   • Risk of bleeding may delay anticoagulation therapy
   • Not useful for prognostication or therapeutic indications 1

3. Differential diagnosis considerations:

   • Heart failure
   • Constrictive pericarditis
   • Circulatory failure
   • Sinusoidal obstruction syndrome 1

4. Timing considerations:

   • Consider renal toxicity of iodinated contrast agents when planning invasive diagnostic procedures
   • Account for possible need for rapid anticoagulation following diagnostic procedures 1

By following this diagnostic approach, hepatic vein thrombosis can be accurately diagnosed, allowing for prompt initiation of appropriate treatment to improve outcomes and reduce mortality.