What is the recommended treatment for a patient with psoriasis and elevated liver enzymes?

Treatment of Psoriasis in a Patient with Elevated Liver Enzymes

For a patient with psoriasis and significantly elevated liver enzymes (ALT 314, AST 104), biologic therapy, particularly an IL-17 or IL-23 inhibitor, is the recommended treatment option as these medications have minimal hepatotoxic effects and can effectively manage psoriasis while allowing liver enzyme normalization. 1, 2

Assessment of Liver Function

The patient's liver enzyme elevations (ALT 314, AST 104) represent a significant abnormality that requires careful consideration when selecting psoriasis treatment. These values are more than 3-fold above the upper limit of normal, indicating substantial liver inflammation that could be due to:

• Psoriasis itself (associated with increased risk of NAFLD)
• Metabolic factors (obesity, diabetes, dyslipidemia)
• Alcohol consumption
• Previous medications
• Other liver conditions

Liver Disease in Psoriasis Patients

Patients with psoriasis have a significantly higher risk of liver abnormalities:

• 65.6% of psoriasis patients may have NAFLD compared to 35% of controls 2
• Psoriasis patients receiving systemic therapy have nearly twice the risk (aHR 1.97) of developing NAFLD compared to the general population 2
• The incidence of hepatic fibrosis in psoriasis patients receiving methotrexate is twice that of rheumatoid arthritis patients on the same medication 2

Treatment Options Analysis

Traditional Systemic Agents to AVOID:

1. Methotrexate:

   • Contraindicated due to significant hepatotoxicity risk
   • With ALT >3x upper limit of normal, guidelines recommend close monitoring and dose reduction 2
   • Persistent elevations require GI consultation and possible liver biopsy 2
   • Patients with psoriasis have higher risk of methotrexate-induced hepatotoxicity than those with rheumatoid arthritis 2

2. Acitretin:

   • Can cause liver enzyme elevations in up to 16% of patients 2
   • Not recommended with pre-existing liver dysfunction 2

3. Leflunomide:

   • Associated with severe liver injury
   • Most cases occur within 6 months of therapy 2

4. Cyclosporine:

   • While not primarily hepatotoxic, it has significant nephrotoxicity
   • Typically used only as short-term "rescue" therapy 2

RECOMMENDED TREATMENTS:

1. Biologic Therapies:

   • IL-17 inhibitors (ixekizumab, secukinumab) or IL-23 inhibitors (guselkumab, risankizumab):
     • Minimal impact on liver function
     • Real-world evidence shows that patients with elevated baseline LFTs experienced significant improvement in liver enzymes after treatment with biologics 3
     • High efficacy for psoriasis with PASI 90 achievement in many patients 1

2. Apremilast:

   • Small molecule with minimal hepatotoxicity
   • Real-world data shows no significant impact on liver function tests 3
   • Less efficacious than biologics but safer for liver concerns

Treatment Algorithm

1. First-line (for moderate-severe psoriasis with elevated liver enzymes):

   • IL-23 inhibitor (risankizumab or guselkumab) or IL-17 inhibitor (ixekizumab or secukinumab)
   • These have shown improvement in liver enzymes in patients with baseline elevations 3

2. Second-line:

   • Apremilast (if biologics are contraindicated or unavailable)
   • Targeted phototherapy (excimer laser or NB-UVB) for localized disease 2

3. Monitoring:

   • Baseline liver function tests, complete blood count
   • Follow-up liver function tests at 3 months and 6 months
   • Consider FIB-4 index calculation to assess fibrosis risk 2
   • Gastroenterology consultation if liver enzymes remain elevated after 3 months

Important Considerations

• Avoid alcohol consumption completely until liver enzymes normalize
• Address metabolic comorbidities (weight management, diabetes control, dyslipidemia treatment)
• Consider non-invasive fibrosis assessment (FIB-4, Fibroscan) to evaluate for advanced liver disease 2
• Avoid NSAIDs which may exacerbate liver inflammation

Common Pitfalls to Avoid

1. Delaying systemic therapy due to liver concerns - recent evidence suggests that appropriate systemic therapy may actually improve liver function in psoriasis patients 3

2. Using methotrexate despite elevated liver enzymes - this significantly increases the risk of progressive liver fibrosis and cirrhosis 2

3. Failing to investigate the cause of liver enzyme elevation - workup should include screening for viral hepatitis, autoimmune hepatitis, and imaging to assess for NAFLD

4. Overlooking drug interactions - some medications used to treat comorbidities may interact with psoriasis treatments and further impact liver function

By following this approach, the patient can receive effective psoriasis treatment while minimizing the risk of further liver damage and potentially allowing liver enzyme normalization.