Are oral ulcers (mouth ulcers) related to abnormal Liver Function Tests (LFTs)?

Relationship Between Oral Ulcers and Liver Function Tests

Oral ulcers can be associated with abnormal liver function tests (LFTs) in several clinical contexts, particularly in patients with underlying liver disease, immune-related conditions, or as a side effect of medications used to treat liver conditions.

Connection Between Oral Ulcers and Liver Disease

Oral ulcers may be related to abnormal liver function tests through several mechanisms:

Direct Associations:

1. Manifestation of Underlying Conditions

   • Oral ulcers can be a manifestation of immune-mediated disorders that also affect the liver 1
   • In inflammatory bowel disease (IBD), which is associated with primary sclerosing cholangitis (PSC), oral ulcers may occur as an extraintestinal manifestation 1

2. Medication-Induced

   • Immunosuppressive medications used for liver transplantation or autoimmune liver diseases can cause oral ulcers
   • Tacrolimus can cause oral ulcers at higher doses, with resolution occurring when doses are reduced 2
   • Mycophenolate mofetil (MMF), used in liver transplant patients, has been documented to cause oral ulcers that resolve after medication discontinuation 3

3. Immune Checkpoint Inhibitor Therapy

   • In patients receiving immune checkpoint inhibitors that can cause hepatitis, mouth ulcers may be associated with enterocolitis as part of immune-related adverse events 1

4. Advanced Liver Disease

   • In patients with cirrhosis, oral mucosal lesions including ulcers are common (74% in one pediatric study) 4
   • More advanced liver disease (Child-Pugh class B/C) is associated with higher rates of oral manifestations compared to less severe disease (Child-Pugh class A) 4

Clinical Implications and Management

Assessment of Patients with Oral Ulcers:

1. Liver Function Evaluation

   • Consider checking LFTs in patients with persistent oral ulcers, especially when:
     • There are other systemic symptoms
     • The patient is on hepatotoxic medications
     • There is a history of autoimmune disease
     • The ulcers are recurrent or non-healing 1, 5

2. Medication Review

   • Review all medications that could affect both liver function and oral mucosa
   • Consider dose adjustment of immunosuppressants if they are suspected to cause oral ulcers 2

Management of Patients with Abnormal LFTs and Oral Ulcers:

1. Identify Underlying Cause

   • Perform a thorough evaluation to determine if both the oral ulcers and abnormal LFTs stem from the same underlying condition 1
   • Consider autoimmune conditions, viral infections, and drug reactions

2. Medication Adjustment

   • For medication-induced oral ulcers in patients with liver disease:
     • Consider reducing the dose of the suspected medication if possible 2
     • Switch to alternative medications with less impact on oral mucosa

3. Symptomatic Treatment

   • Topical treatments for oral ulcers (e.g., benzocaine 20%) can provide symptomatic relief 5
   • Address both the oral manifestations and the underlying liver condition

Special Considerations

Immune Checkpoint Inhibitor Therapy:

• In patients receiving immunotherapy who develop both hepatitis and oral ulcers, this may indicate immune-related adverse events affecting multiple organ systems 1
• Management typically involves withholding the immunotherapy and initiating corticosteroids 1

Liver Transplant Recipients:

• Oral ulcers in liver transplant recipients may be due to:
  • Immunosuppressive medications (particularly tacrolimus and MMF) 2, 3
  • Opportunistic infections due to immunosuppression
  • Recurrence of the underlying disease that led to transplantation

When to Refer

• Persistent oral ulcers (>2 weeks) should prompt referral to an oral medicine specialist or oral and maxillofacial surgeon 5
• Patients with abnormal LFTs and oral ulcers may need evaluation by both hepatology and oral medicine specialists
• Any suspicious oral lesions should be biopsied to rule out malignancy, particularly in patients with chronic liver disease 5

Conclusion

While not all oral ulcers indicate liver dysfunction, their presence—especially when persistent or recurrent—should prompt consideration of underlying systemic conditions, including liver disease. Conversely, patients with known liver disease who develop oral ulcers should have careful evaluation to determine whether the ulcers are related to their liver condition, medications, or represent a separate issue requiring specific management.