What can cause elevation of Liver Function Tests (LFTs) after starting systemic corticosteroids (steroids)?

Causes of LFT Elevation After Starting Systemic Steroids

Systemic corticosteroids themselves can directly cause liver function test elevations through multiple mechanisms, including drug-induced liver injury, immune-mediated hepatitis, and metabolic effects.

Primary Mechanisms of Steroid-Induced LFT Elevation

1. Direct Drug-Induced Liver Injury (DILI)

• Corticosteroids can cause hepatotoxicity, though this is relatively rare compared to other medications 1
• Presentation typically occurs within 1-6 weeks after starting therapy 1
• Can manifest as:
  • Elevated transaminases (AST/ALT)
  • Cholestatic pattern with elevated alkaline phosphatase
  • Rarely, acute liver failure 2

2. Immune-Mediated Mechanisms

• Paradoxical autoimmune-like hepatitis triggered by steroids 1
• Methylprednisolone has been specifically associated with drug-induced autoimmune-like hepatitis 1
• May present with:
  • Marked transaminase elevation
  • Positive autoantibodies in some cases
  • Liver biopsy showing lymphocytic infiltration

3. Metabolic Effects

• Steroids can cause or exacerbate fatty liver disease through:
  • Insulin resistance
  • Weight gain
  • Dyslipidemia
  • Altered hepatic lipid metabolism 1

Confounding Factors When Evaluating LFT Elevation

1. Underlying Disease Activity

• The condition being treated with steroids may itself cause LFT abnormalities
• Autoimmune conditions like inflammatory bowel disease can have hepatic manifestations 1
• Immune checkpoint inhibitor therapy often requires steroids and can independently cause hepatitis 1

2. Concomitant Medications

• Many patients on steroids are taking multiple medications
• Drug interactions may potentiate hepatotoxicity
• Altered metabolism of other medications due to steroid effects 3

3. Exercise-Induced Transaminase Elevation

• Intense physical activity can elevate AST/ALT without true hepatic dysfunction
• Important to check gamma-glutamyltranspeptidase (GGT) and creatine kinase (CK) 4
• GGT remains normal in exercise-induced transaminase elevation but rises in true hepatitis

Diagnostic Approach for LFT Elevation After Starting Steroids

1. Assess pattern of LFT abnormality:

   • Hepatocellular (predominant AST/ALT elevation)
   • Cholestatic (predominant alkaline phosphatase/GGT elevation)
   • Mixed pattern

2. Rule out other common causes:

   • Viral hepatitis (test for hepatitis A, B, C, E)
   • Alcohol consumption
   • Other hepatotoxic medications
   • Underlying liver disease progression 5

3. Specific tests to consider:

   • Complete blood count with platelets
   • Comprehensive metabolic panel
   • GGT and creatine kinase to differentiate muscle injury from liver injury
   • Autoimmune markers (ANA, ASMA) if autoimmune hepatitis suspected 1
   • Hepatobiliary imaging to rule out biliary obstruction 1

Management Recommendations

1. For mild elevations (< 3× ULN):

   • Continue monitoring LFTs every 1-2 weeks 5
   • Consider dose reduction if clinically appropriate

2. For moderate elevations (3-5× ULN):

   • Consider temporary dose reduction
   • More frequent monitoring (weekly)
   • Evaluate for alternative causes 5

3. For severe elevations (> 5× ULN) or symptoms:

   • Discontinue steroids if possible or reduce to lowest effective dose
   • Consider hepatology consultation
   • Rule out other causes of acute liver injury 1

Special Considerations

• Steroid metabolism in liver disease: Patients with active liver disease may have impaired conversion of prednisone to prednisolone (the active form) and altered plasma protein binding, resulting in different levels of biologically active corticosteroids 3

• Rechallenge considerations: If steroids must be restarted after LFT normalization, consider using a different corticosteroid preparation or lower dose with close monitoring 1

• Anabolic steroids: These cause more severe hepatotoxicity than therapeutic corticosteroids, particularly 17-α-alkylated derivatives, which can cause cholestatic injury, vascular injury, and tumors 6

Remember that while corticosteroid-induced liver injury is possible, it's relatively uncommon compared to other medications, and alternative causes should always be thoroughly investigated before attributing LFT elevations solely to steroid therapy.