Management of Abnormal LFTs in Post-Renal Transplant Patient on Tacrolimus and Azathioprine
Immediately check tacrolimus trough levels (target 4-8 ng/mL), obtain a complete viral hepatitis panel (CMV PCR, EBV PCR, hepatitis A IgM, hepatitis B surface antigen and core antibody, hepatitis C antibody and RNA), perform a complete blood count to assess for azathioprine-induced bone marrow suppression, and strongly consider discontinuing azathioprine given the cholestatic pattern of liver injury (elevated ALP with modest transaminase elevation) which is characteristic of azathioprine hepatotoxicity. 1
Immediate Diagnostic Workup
The cholestatic pattern (ALP 349 with direct bilirubin 1.0 and modest SGOT 60) raises strong suspicion for azathioprine-induced cholestatic hepatitis, which is dose-dependent and associated with high 6-methylmercaptopurine metabolite levels. 1 However, viral etiologies must be excluded first:
Obtain tacrolimus trough level immediately - target range should be 4-8 ng/mL in this patient who is more than 12 months post-transplant. 1, 2 Given his creatinine of 1.19, tacrolimus nephrotoxicity may be contributing to both renal and hepatic issues.
Complete viral hepatitis panel is mandatory including CMV PCR, EBV PCR, hepatitis A IgM, hepatitis B surface antigen and core antibody, hepatitis C antibody and RNA. 1 The history of food consumption followed by gastrointestinal symptoms raises concern for viral hepatitis acquisition.
Check complete blood count to assess for leucopenia or thrombocytopenia, which would indicate azathioprine-induced bone marrow suppression. 1 This is critical as azathioprine toxicity can manifest with both hepatic and hematologic abnormalities.
Azathioprine Management Decision
If viral serologies are negative and CBC shows no contraindication, discontinue azathioprine immediately. 1 The cholestatic pattern strongly suggests azathioprine hepatotoxicity, which is a well-recognized complication:
Azathioprine causes cholestatic hepatitis that is dose-dependent, and this patient is on 200 mg daily (100 mg twice daily), which is a substantial dose. 1
The temporal relationship (symptoms starting one month ago with persistent LFT abnormalities) fits the pattern of drug-induced liver injury.
Continuation of azathioprine in the setting of suspected hepatotoxicity risks progression to more severe liver injury.
Immunosuppression Adjustment After Azathioprine Withdrawal
Add mycophenolate mofetil 500-1000 mg twice daily to replace azathioprine, and reduce tacrolimus target trough to 3-5 ng/mL. 1 This approach maintains adequate immunosuppression while removing the hepatotoxic agent:
Increase tacrolimus monitoring frequency after azathioprine withdrawal to ensure therapeutic levels are maintained. 1
The combination of mycophenolate mofetil with reduced tacrolimus dosing provides effective immunosuppression while minimizing both hepatotoxicity and nephrotoxicity. 1
Avoid NSAIDs and other nephrotoxic drugs that could potentiate tacrolimus-induced nephrotoxicity, especially given the baseline creatinine of 1.19. 1
Monitoring for Rejection
Monitor closely for signs of rejection after medication changes including:
- Rising creatinine above baseline of 1.19 1
- New onset proteinuria 1
- Declining graft function 1
- Screen for donor-specific antibodies as de novo DSAs indicate subclinical rejection risk 1
Follow-up LFT Monitoring
- Repeat LFTs in 1-2 weeks after azathioprine discontinuation to confirm improvement
- If LFTs worsen or fail to improve after azathioprine withdrawal, consider liver biopsy to evaluate for other etiologies including viral hepatitis, drug-induced liver injury from tacrolimus, or de novo liver disease
Critical Pitfall to Avoid
Do not continue azathioprine while "monitoring" LFTs - the cholestatic pattern with this dose of azathioprine (200 mg daily) in the setting of normal imaging strongly suggests drug-induced injury that will not resolve without medication discontinuation. 1 The risk of continued hepatotoxicity outweighs the theoretical risk of rejection during the transition to mycophenolate mofetil, especially in a patient who is 12 years post-transplant with stable graft function.