What is Mast Cell Activation Syndrome (MCAS) related liver dysfunction?

Mast Cell Activation Syndrome (MCAS) Related Liver Dysfunction

Mast Cell Activation Syndrome (MCAS) related liver dysfunction is characterized primarily by elevated cholesterol levels (75% of cases), elevated transaminases (40%), elevated bilirubin (36%), and hepatomegaly or morphological hepatic alterations (34%) resulting from inappropriate release of inflammatory mediators from mast cells affecting liver function. 1

Pathophysiology of MCAS-Related Liver Dysfunction

• MCAS is defined as a primary clinical condition with spontaneous episodic signs and symptoms affecting at least 2 organ systems resulting from secreted mast cell mediators 2
• Mast cells release inflammatory mediators including histamine, prostaglandin D2, and leukotriene C4, which can affect multiple organ systems including the liver 2
• Liver dysfunction in MCAS appears to be related to Kupffer cell activation in the liver, though chitotriosidase levels (a surrogate marker) remain unchanged in blood 1
• Mast cells in MCAS patients show downregulated chitotriosidase expression at the mRNA level, which may be a marker of mast cell activation affecting liver function 1

Clinical Manifestations of MCAS-Related Liver Dysfunction

• Hypercholesterolemia is the most common liver-related finding (75% of cases) 1
• Elevated liver enzymes (transaminases) occur in approximately 40% of MCAS patients 1
• Elevated bilirubin levels are present in 36% of cases 1
• Hepatomegaly or morphological hepatic alterations are observed in 34% of patients 1
• These liver abnormalities may occur alongside other systemic manifestations of MCAS affecting cardiovascular, dermatologic, respiratory, and gastrointestinal systems 2

Diagnostic Approach for MCAS-Related Liver Dysfunction

• Diagnosis requires documentation of:
  • Recurrent episodes of systemic symptoms affecting at least 2 organ systems 2
  • Elevated levels of mast cell mediators during symptomatic episodes 2
  • Response to medications targeting mast cell mediators 2
• Laboratory evaluation should include:
  • Comprehensive metabolic panel with liver function tests (LFTs) 2
  • Serum tryptase level (baseline and during acute episodes) 2
  • Urine N-methylhistamine, 11β-PGF2α, and LTE4 levels 2
• Liver-specific evaluation:
  • Cholesterol profile 1
  • Transaminases and bilirubin 1
  • Imaging studies (CT/MRI or ultrasound) to assess hepatomegaly 2

Differential Diagnosis

• Primary MCAS must be distinguished from:
  • Secondary MCAS (allergies, drugs, infections) 2
  • Systemic mastocytosis (requires bone marrow biopsy) 2
  • Hereditary alpha-tryptasemia 2
  • Metabolic dysfunction-associated steatotic liver disease (MASLD) 2
  • Other causes of liver enzyme elevation 2

Management of MCAS-Related Liver Dysfunction

• Treatment focuses on controlling mast cell activation with:
  • H1 and H2 histamine receptor antagonists 2
  • Mast cell stabilizers 2
  • Leukotriene receptor antagonists 2
  • COX inhibitors to decrease prostaglandin production 2
• Specific management of liver dysfunction:
  • Monitor liver function tests regularly 1
  • Address hypercholesterolemia if present 1
  • Avoid hepatotoxic medications when possible 3
• Multidisciplinary approach involving hepatology and allergy/immunology specialists 2

Prognosis and Complications

• Liver abnormalities in MCAS are typically chronic but may fluctuate with disease activity 1
• Early recognition of MCAS as a cause of liver dysfunction can prevent unnecessary invasive procedures 1
• Untreated MCAS-related liver dysfunction may contribute to long-term hepatic complications, though specific long-term outcomes are not well-documented 1

Clinical Pearls and Pitfalls

• MCAS should be considered as a possible cause of unexplained liver abnormalities, particularly when accompanied by symptoms in other organ systems 1
• Hypercholesterolemia without other obvious causes may be an early indicator of MCAS-related liver dysfunction 1
• Avoid misdiagnosing MCAS in patients with other conditions that may explain liver dysfunction 4
• Patients with MCAS undergoing procedures or surgery require special anesthetic considerations to prevent mast cell activation 5
• Research is still needed to fully understand the mechanisms and optimal management of MCAS-related liver dysfunction 6