Does Cyclosporine Cause Deranged LFT?
Yes, cyclosporine commonly causes mild elevations in liver function tests, particularly alkaline phosphatase and bilirubin, occurring in approximately 32-58% of patients, though these abnormalities are typically mild, transient, and self-limited. 1, 2
Incidence and Pattern of Liver Function Abnormalities
Biochemical liver abnormalities occur in 32-58% of cyclosporine-treated patients, with the most common pattern being mild cholestatic injury characterized by elevated alkaline phosphatase and bilirubin. 2
The British Association of Dermatologists guidelines specifically note that cyclosporine therapy often induces small increases in serum bilirubin as part of its expected biochemical effects, which only occasionally cause clinical concern. 1
In transplant populations, hepatotoxicity manifested by elevations of hepatic enzymes and bilirubin was reported in 4% of renal transplant patients, 7% of cardiac transplant patients, and 4% of liver transplant patients in clinical trials. 3
Characteristics of Cyclosporine-Induced Liver Injury
Peak alkaline phosphatase levels typically range from 125 to 243 units/liter and can persist from seven days to 48 months, though most cases are self-limited and asymptomatic. 2
The liver enzyme elevations usually occur during the first month of therapy when high doses are used and typically decrease with dose reduction. 3
The pattern is predominantly cholestatic rather than hepatocellular, with alkaline phosphatase and bilirubin being more commonly affected than transaminases. 2
Clinical Significance and Monitoring
The American Academy of Dermatology and British Association of Dermatologists both recommend baseline liver function tests before initiating cyclosporine, followed by monthly monitoring during treatment. 1
These abnormalities may cause diagnostic difficulty if preexisting liver disease is present, as the mild elevations can be confused with progression of underlying hepatic pathology. 2
The FDA drug label warns that cases of hepatotoxicity and liver injury including cholestasis, jaundice, hepatitis and liver failure have been reported, though most cases involved patients with significant comorbidities and confounding factors, with some fatal outcomes reported mainly in transplant patients. 3
Special Populations at Higher Risk
Patients with preexisting liver disease may experience more severe hepatotoxicity with cyclosporine, though the evidence is mixed. One study found no significant difference in hepatobiliary dysfunction between patients receiving cyclosporine versus those not receiving it when both groups were on total parenteral nutrition. 4
Patients with severe liver disease may have significantly reduced cyclosporine clearance, necessitating dose reduction to maintain blood concentrations within the recommended target range. 3
Comparison with Other Calcineurin Inhibitors
- Tacrolimus may actually have higher risk of inducing liver injury compared to cyclosporine in patients with a history of liver disease, with one study showing tacrolimus-treated patients had ALT levels of 153 IU/L versus 65 IU/L in cyclosporine-treated patients with liver disease history. 5
Clinical Management Approach
When liver enzyme elevations occur, dose reduction is the primary management strategy, as the chemistry elevations usually decrease with dosage adjustment. 3
Monitoring should include assessment of alkaline phosphatase, bilirubin, and transaminases, with particular attention to the cholestatic pattern of injury. 1
The abnormalities typically resolve once cyclosporine is discontinued or the dose is reduced, confirming the reversible nature of cyclosporine-induced hepatotoxicity in most cases. 2
Important Caveats
The hepatotoxicity is usually mild and does not require discontinuation of therapy in most patients, distinguishing it from the more serious nephrotoxicity that cyclosporine can cause. 2
Severe hepatotoxicity with clinical consequences is rare in dermatologic and rheumatologic patients, with most serious cases occurring in transplant populations with multiple confounding factors. 3
Drug interactions through the cytochrome P450 3A4 system can alter cyclosporine metabolism and potentially affect liver enzyme patterns, requiring careful review of concomitant medications. 1