What are the causes of hepatomegaly and spleenomegaly?

Causes of Hepatomegaly and Splenomegaly

Hepatomegaly and splenomegaly are most commonly caused by metabolic storage disorders, infectious diseases, hematologic disorders, and hepatic diseases with portal hypertension, requiring systematic evaluation to determine the underlying etiology. 1, 2

Metabolic Storage Disorders

• Glycogen storage diseases (GSDs) frequently present with hepatomegaly, with some types also causing splenomegaly 3

  • GSD I: Hepatomegaly with hypoglycemia, hyperlactatemia, hyperuricemia, and elevated AST/ALT 3
  • GSD III: Hepatomegaly with fasting hypoglycemia, elevated AST/ALT, hyperlipidemia, and muscle involvement with elevated CK in GSD IIIa 3
  • GSD IV: Hepatomegaly with elevated AST/ALT, prolonged PT, and low albumin in advanced stages 3
  • GSD VI and IX: Hepatomegaly with fasting hypoglycemia, elevated AST/ALT, and hyperlipidemia 3

• Lysosomal storage diseases commonly present with both hepatomegaly and splenomegaly 1, 2, 4

  • Niemann-Pick disease: Significant hepatosplenomegaly, growth failure, hyperlipidemia, and characteristic storage cells 3, 2
  • Gaucher disease: Hepatosplenomegaly with bone and pulmonary involvement 2, 4
  • Acid sphingomyelinase deficiency (ASMD): Can present with massive splenomegaly (>10x normal size) 1, 5
  • Lysosomal acid lipase deficiency (LALD): Hepatosplenomegaly with dyslipidemia 2, 5

Hepatic Diseases

• Wilson disease: Can present with isolated splenomegaly due to clinically inapparent cirrhosis with portal hypertension 3, 2

  • May present with Kayser-Fleischer rings, neurological or psychiatric symptoms 3
  • Various hepatic presentations from asymptomatic hepatomegaly to fulminant hepatic failure 3

• Cirrhosis with portal hypertension: Common cause of splenomegaly regardless of etiology 2

  • Often associated with thrombocytopenia and other signs of portal hypertension 2

• Cystic fibrosis hepatobiliary involvement: Can present with hepatosplenomegaly 3, 5

  • Annual screening with labs and physical examination recommended 3
  • Abdominal ultrasound recommended at least every 2 years in children with CF 3

• Primary liver diseases: Hepatitis, α-1-antitrypsin deficiency present with hepatomegaly and elevated liver enzymes 3

Infectious Causes

• Parasitic infections: Malaria and schistosomiasis are common causes of splenomegaly in tropical regions 2
• Cytomegalovirus infection: Can cause tropical splenomegaly syndrome with massive splenomegaly, hypersplenism, and moderate hepatomegaly 6
• Endocarditis: Can lead to splenic abscess and splenomegaly 1

Hematologic Disorders

• Leukemia and lymphoma: Can present with hepatosplenomegaly 5, 7
  • Acute myeloid leukemia can present with hepatosplenomegaly and infiltration of the liver and spleen 7
• Myeloproliferative disorders: Particularly myelofibrosis, associated with massive splenomegaly 1
• Autoimmune disorders: Including rheumatoid arthritis with Felty syndrome 2

Diagnostic Approach

• Initial laboratory evaluation should include 5:

  • Complete blood count to assess for cytopenias (particularly thrombocytopenia)
  • Liver function tests (total bilirubin, AST, ALT, alkaline phosphatase, GGT)
  • Lipid profile to identify mixed dyslipidemia in storage disorders
  • Blood glucose, lactate, and uric acid levels (especially if GSD suspected) 3

• Imaging studies 3, 5:

  • Abdominal ultrasound to confirm hepatosplenomegaly and assess for other abdominal pathology
  • Liver elastography to assess for fibrosis if available
  • Chest X-ray or CT to evaluate for pulmonary involvement in certain disorders

• Specialized testing based on clinical suspicion 5, 8:

  • Genetic testing for suspected storage disorders
  • Enzymatic analysis on liver biopsy samples for suspected GSD 3
  • Bone marrow biopsy if hematologic disorders are suspected

Clinical Pearls

• Splenomegaly with portal hypertension is often associated with thrombocytopenia 2
• In young adults with unexplained hepatosplenomegaly, lysosomal storage diseases should be considered 5, 4
• Autoimmune hepatitis can present with hepatosplenomegaly, elevated transaminases, and high serum gammaglobulin levels 9
• Hepatomegaly often leads gastroenterologists to perform a liver biopsy, but genetic sequencing may be more appropriate when storage disorders are suspected 3