What is the effect of cyclosporine on liver function tests (LFTs)?

Effect of Cyclosporine on Liver Function Tests (LFTs)

Cyclosporine commonly causes mild, transient elevations in liver function tests, primarily manifesting as hyperbilirubinemia and increased alkaline phosphatase, indicating a cholestatic pattern of liver injury. 1

Specific Effects on LFTs

Common LFT Abnormalities

• Hyperbilirubinemia - Listed as a known toxicity in dermatology guidelines 2
• Elevated alkaline phosphatase - Most common abnormality, with levels typically ranging from 125-243 units/liter 1
• Mild elevations in aminotransferases - Less common than alkaline phosphatase elevations 1

Frequency and Severity

• Approximately 58% of patients develop at least one LFT abnormality during cyclosporine treatment 1
• 32% of patients exhibit prolonged patterns of LFT abnormalities 1
• In transplant patients, hepatotoxicity manifested by elevations in hepatic enzymes and bilirubin was reported in:
  • 4% of renal transplant patients
  • 7% of cardiac transplant patients
  • 4% of liver transplant patients 3

Monitoring Recommendations

The British Association of Dermatologists and American Academy of Dermatology both recommend:

• Baseline assessment: Complete liver function tests before starting therapy 2
• Regular monitoring: Monthly LFTs during treatment 2
• Early monitoring: More frequent monitoring during the first 2-3 months of therapy 2

Management of LFT Abnormalities

When to Adjust Dosage

• If LFTs show abnormalities of clinical concern, reduce cyclosporine dosage by 25-50% 3
• LFT abnormalities typically occur during the first month of therapy when high doses are used 3
• Elevations usually decrease with dose reduction 3

Risk Factors for Hepatotoxicity

• Pre-existing liver disease increases risk of cyclosporine-induced liver injury 1
• Concomitant use of other hepatotoxic medications 3
• High-dose therapy, particularly in the early treatment phase 3

Mechanism of Liver Injury

Cyclosporine-induced liver injury typically presents as:

• Mild cholestatic pattern (elevated alkaline phosphatase and bilirubin) 1
• Histologic changes in liver biopsies associated with elevated cyclosporine levels include:
  • Hypertrophy of bile ductal epithelium with cytoplasmic vacuoles
  • Presence of "foamy" material within hepatic sinusoids 4

Clinical Implications

• Most cyclosporine-induced LFT abnormalities are self-limited and asymptomatic 1
• Cases of hepatotoxicity including cholestasis, jaundice, hepatitis, and liver failure have been reported, though most patients had significant comorbidities or other confounding factors 3
• In some transplant patients, fatal outcomes have been reported, though these are rare 3

Important Considerations

• Drug interactions can significantly affect cyclosporine metabolism and potentially worsen hepatotoxicity 5
• Cyclosporine is extensively metabolized by cytochrome P450 3A4, making it susceptible to numerous drug interactions 5, 3
• Avoid grapefruit juice completely while on cyclosporine as it can inhibit cytochrome P450 3A4 and increase cyclosporine blood levels 2
• St. John's wort and other herbal remedies can interact with cyclosporine and affect its metabolism 2

By understanding cyclosporine's effects on liver function and implementing appropriate monitoring, clinicians can minimize the risk of significant hepatotoxicity while maintaining therapeutic efficacy.