What tests are used to diagnose hepatosplenomegaly?

Diagnostic Tests for Hepatosplenomegaly

The most effective diagnostic approach for hepatosplenomegaly begins with abdominal ultrasound, followed by complete blood count, liver function tests, and specialized testing based on initial findings. 1

Initial Diagnostic Tests

• Abdominal ultrasound is the first-line imaging test to confirm and characterize hepatosplenomegaly, assess liver morphology, identify focal lesions, and detect signs of portal hypertension 1, 2
• Complete blood count (CBC) is essential to assess for cytopenias, particularly thrombocytopenia, which may indicate portal hypertension or hematologic disorders 1, 3
• Liver function tests help evaluate hepatic involvement and guide further diagnostic workup 1, 4
• Lipid profile can identify mixed dyslipidemia with decreased HDL, which is common in storage disorders like acid sphingomyelinase deficiency (ASMD) 1, 3

Specialized Imaging Tests

• Doppler ultrasonography provides valuable information about portal blood flow and can detect portal hypertension by identifying reduced portal blood flow velocity, loss of respiratory changes in portal flow, or portal blood flow reversal 5
• Computed tomography (CT) or MRI can provide detailed assessment of liver and spleen morphology and detect portosystemic shunting (recanalization of umbilical vein, esophageal varices, gastric varices, spleen-kidney shunt) 5
• Chest X-ray or CT should be considered to evaluate for pulmonary involvement, especially if storage disorders are suspected 1, 5

Advanced Diagnostic Tests

• Vibration-controlled transient elastography (VCTE) can assess liver stiffness and has excellent diagnostic performance for clinically significant portal hypertension with a hierarchical summary AUC of 0.90 5
• LSPS score (combining liver stiffness, spleen size, and platelet count) improves diagnostic accuracy for portal hypertension 5
• Hepatic venous pressure gradient (HVPG) measurement is the gold standard for assessing portal hypertension but is invasive and limited to specialized centers 5
• Genetic testing, particularly for the SMPD1 gene, should be considered if there is clinical suspicion of ASMD 1, 6
• Bone marrow biopsy may be necessary if hematologic disorders are suspected or to identify storage cells 1, 7
• Liver biopsy can be helpful in cases where non-invasive tests are inconclusive, but should be avoided in suspected hereditary hemorrhagic telangiectasia due to bleeding risk 5

Diagnostic Algorithm Based on Clinical Presentation

1. For all patients with suspected hepatosplenomegaly:

   • Begin with abdominal ultrasound to confirm organomegaly 1
   • Perform CBC, liver function tests, and lipid profile 1, 4

2. If portal hypertension is suspected:

   • Add Doppler ultrasound to assess portal blood flow 5
   • Consider VCTE if available (values >20-25 kPa suggest clinically significant portal hypertension) 5

3. If storage disorder is suspected:

   • Genetic testing for SMPD1 (ASMD), GBA (Gaucher), NPC1/NPC2 (Niemann-Pick C) 1, 6
   • Consider bone marrow biopsy to identify storage cells 1

4. If infectious cause is suspected:

   • Add appropriate serological tests for viral, bacterial, or parasitic infections 4, 8
   • Consider blood cultures if fever is present 2

Important Clinical Considerations

• Splenomegaly in storage disorders like ASMD can be massive (>10x normal size) and may precede hepatomegaly 2
• Liver biopsy should be avoided in suspected hereditary hemorrhagic telangiectasia as it carries significant bleeding risk and provides less information than imaging studies 5
• Serum markers alone (APRI, FIB-4, Forns index, Lok score) have limitations in evaluating portal hypertension and should be combined with imaging findings 5
• In young adults with unexplained hepatosplenomegaly, consider ASMD which often has a 4+ year delay in diagnosis due to its rarity 1, 5