How to manage psoriasis in a patient with transaminitis (elevated liver enzymes)?

Managing Psoriasis with Transaminitis

In patients with psoriasis and elevated liver enzymes, prioritize biologics (TNF-alpha inhibitors, IL-12/23 inhibitors, or IL-17 inhibitors) over traditional systemic agents like methotrexate, acitretin, or cyclosporine, as biologics have minimal hepatotoxic potential and recent evidence shows they may actually improve liver function tests over time. 1, 2

Initial Assessment and Risk Stratification

Before selecting therapy, determine the underlying cause and severity of transaminitis:

• Identify the etiology of elevated liver enzymes: Common causes in psoriasis patients include non-alcoholic fatty liver disease (NAFLD) (22% of cases), drug-induced hepatitis (57% of cases), alcohol consumption, viral hepatitis, or autoimmune liver disease 3, 4
• Assess metabolic comorbidities: Obesity, diabetes mellitus, dyslipidemia, and metabolic syndrome significantly increase risk of liver disease in psoriasis patients 3, 4
• Quantify the degree of elevation: Mild transaminase elevations (1-2x upper normal limit) versus moderate-severe elevations (>2-3x upper normal limit) guide treatment selection 5
• Calculate FIB-4 score to assess for underlying fibrosis risk, particularly if NAFLD is suspected 2
• Screen for viral hepatitis B and C, alcohol use history, and review all current medications for hepatotoxic potential 6, 3

Treatment Selection Algorithm

First-Line: Biologic Therapy

Biologics are the preferred systemic treatment for psoriasis patients with transaminitis because they lack direct hepatotoxic effects and do not require intensive liver monitoring 1, 2:

• TNF-alpha inhibitors (adalimumab, etanercept): No known deleterious effects on liver function, no drug interactions affecting hepatic metabolism, and no impact on renal function or blood pressure 1
• IL-12/23 inhibitors (ustekinumab, risankizumab): Excellent safety profile in patients with baseline liver abnormalities 1, 7
• IL-17 inhibitors (secukinumab, ixekizumab): Recent real-world evidence demonstrates these agents do not worsen liver function and may allow improvement in elevated transaminases over 3-6 months 2

Key evidence: A 2025 real-world study of 278 patients showed that those with elevated baseline liver enzymes experienced significant decreases in AST, ALT, and GGT during treatment with secukinumab, ixekizumab, adalimumab, or apremilast, with no increase in FIB-4 scores 2. This directly contradicts the traditional concern about avoiding systemic therapy in patients with liver abnormalities.

Agents to Avoid or Use with Extreme Caution

Methotrexate is relatively contraindicated in patients with pre-existing transaminitis:

• The FDA label explicitly states "special caution is indicated in the presence of preexisting liver damage or impaired hepatic function" 5
• Methotrexate causes both acute hepatotoxicity (elevated transaminases) and chronic hepatotoxicity (fibrosis and cirrhosis after cumulative doses >1.5 grams) 5
• If methotrexate must be used: Obtain baseline liver biopsy in patients with pre-existing liver abnormalities, perform weekly liver function tests initially, then every 1-2 months if stable 1, 6, 5
• Persistent liver function test abnormalities mandate liver biopsy or drug discontinuation 5

Acitretin (retinoids) should be avoided:

• Up to 16% of acitretin-treated patients develop serum transaminase elevations 1
• 25-50% develop triglyceride elevations, compounding metabolic liver disease risk 1
• These effects are dose-dependent and particularly problematic in patients with obesity, diabetes, or baseline NAFLD 1

Cyclosporine has significant limitations:

• While not directly hepatotoxic, cyclosporine has numerous drug interactions via cytochrome P450 3A4 that can affect liver metabolism 1
• Should be reserved as short-term "rescue" therapy only (maximum 1 year continuous use) 1
• Particularly problematic in patients with metabolic syndrome comorbidities common in those with NAFLD 1

Second-Line: Phototherapy

Narrowband UVB phototherapy is a reasonable option for patients with transaminitis who cannot access biologics:

• No hepatotoxic effects and does not require liver function monitoring 7
• Can be administered 2-3 times weekly with appropriate baseline skin cancer screening 7
• Less effective than biologics but safer than traditional systemic agents in the setting of liver disease 1, 7

Monitoring Strategy

For patients on biologic therapy with baseline transaminitis:

• Recheck liver enzymes at 3 and 6 months: Evidence shows improvement rather than worsening in most cases 2
• Monitor for infection risk: Biologics increase opportunistic infection risk, though not specifically liver-related 1
• Continue monitoring metabolic parameters: Address underlying NAFLD through weight loss, diabetes control, and lipid management 3, 4

For patients requiring methotrexate despite transaminitis (rare circumstances):

• Weekly monitoring initially: Full blood count, liver function tests, serum creatinine 1, 6
• Baseline liver biopsy strongly recommended before initiating therapy 1, 5
• Repeat biopsy at cumulative dose of 1.5 grams, then every additional 1-1.5 grams 5
• Discontinue if persistent abnormalities or if biopsy shows moderate-severe changes (Roenigk grade IIIb or IV) 5

Critical Pitfalls to Avoid

• Do not reflexively avoid systemic therapy: Elevated liver enzymes in psoriasis patients often reflect disease severity and metabolic comorbidities rather than contraindications to treatment 2, 4
• Do not assume drug causation: In severe psoriasis flares, 36% of patients have elevated liver enzymes, with specific psoriatic inflammation (particularly in pustular psoriasis) contributing independently of medications 4
• Do not use systemic corticosteroids: These can precipitate erythrodermic or pustular psoriasis and worsen metabolic syndrome 6
• Avoid alcohol and hepatotoxic drug combinations: Methotrexate interactions with NSAIDs, alcohol, trimethoprim, and other agents can cause severe hepatotoxicity 1, 5

Special Populations

Women of childbearing potential with transaminitis:

• Acitretin is absolutely contraindicated due to 3-year teratogenic risk and high likelihood of worsening liver function 1
• Methotrexate requires reliable contraception and is generally avoided 7
• Biologics remain the safest option, though pregnancy planning requires individual agent consideration 1, 7