Immunosuppression, Rejection, and Post-Transplant Complications
Immunosuppression
Most pediatric liver recipients receive a calcineurin inhibitor (tacrolimus or cyclosporine), often with mycophenolate and a steroid taper. Tacrolimus is monitored by trough levels; goal levels decline over time. Induction may use basiliximab or corticosteroids. Mycophenolate is teratogenic and causes GI and marrow toxicity; mTOR inhibitors impair wound healing and can cause hyperlipidemia and proteinuria.
Rejection
Acute cellular rejection typically occurs in the first months and presents with fever, malaise, rising transaminases or bilirubin, and biopsy findings of mixed portal inflammation, bile duct injury, and endothelialitis. Treat with pulse corticosteroids and adjust maintenance; steroid-resistant rejection may require antithymocyte globulin. Antibody-mediated rejection is less common and may need plasmapheresis and IVIG. Chronic rejection shows ductopenia and arteriopathy and often leads to graft loss.
Complications and traps
Distinguish rejection from infection, biliary stricture, vascular thrombosis, recurrent disease, and drug toxicity. Rejection can be asymptomatic; do not treat a rising level alone without evaluation. Tacrolimus nephrotoxicity and neurotoxicity are common. EBV viremia and PTLD require reducing immunosuppression. Adherence is the major cause of late rejection.
Worked example
A 12-year-old 8 months post-transplant has ALT 240 U/L, AST 180 U/L, bilirubin 1.8 mg/dL, and tacrolimus trough 3 ng/mL with target 5 to 8. Check EBV and CMV, Doppler, and biliary imaging; then biopsy. If biopsy shows acute cellular rejection, give steroid pulse, restore target immunosuppression, and investigate nonadherence.
Rule of thumb: biopsy before treating rejection unless the patient is unstable.