Immunosuppression, Acute and Chronic Rejection, and Transplant Immunology
The immune problem
The liver is unusually tolerogenic - HLA matching is not required, and some recipients can eventually withdraw immunosuppression - but most need lifelong therapy. Standard maintenance is a calcineurin inhibitor (tacrolimus first-line) plus an antimetabolite (mycophenolate), with steroids tapered over weeks to months. Induction with basiliximab (IL-2 receptor antagonist) or antithymocyte globulin is used for renal-sparing or high-immunologic-risk patients. mTOR inhibitors (sirolimus, everolimus) are avoided in the first month because of hepatic artery thrombosis and wound-healing complications.
Acute cellular rejection occurs in 20-30% of patients, mostly within the first 3 months. Biopsy shows the triad of mixed portal inflammation, bile duct injury, and subendothelial venulitis (Banff criteria). First-line treatment is high-dose methylprednisolone; steroid-resistant rejection gets antithymocyte globulin. Chronic rejection (ductopenic rejection) shows vanishing bile ducts and foam-cell arteriopathy and is usually irreversible; prevention is adequate maintenance immunosuppression and adherence.
Traps: do not treat a rising alkaline phosphatase with empirical steroids - biopsy first. Do not diagnose rejection when the patient has a biliary stricture, hepatic artery thrombosis, or recurrent disease. Tacrolimus toxicity includes nephrotoxicity, tremor, and hyperkalemia; it is a CYP3A4 substrate, so azoles raise levels and rifampin lowers them.
Rule of thumb: biopsy-proven rejection before escalating - and always check a tacrolimus trough and Doppler ultrasound first.