**11. Rejection**

Acute cellular rejection (ACR), usually mediated by T-cells, has decreased in recent years with the use of improved potent immunosuppressants, but still ranges from 15 to 25% and usually occurs 7–14 days after surgery [94]. Hyperacute liver rejection is controversial, but undoubtedly early accelerated rejection occurs in the first 7 days and is associated with preformed antibodies. Risk factors include adequacy, type, and level of immunosuppression, underlying immune disease, biliary complications, certain transplant-related features such as donor-negative recipient-positive CMV mismatch, sex mismatch with a female donor. ACR is not significantly associated with long-term graft failure unless it concerns HCV-positive patients in which case it may result in corticosteroid-resistant rejection and graft loss. Early ACR is associated with better graft outcomes [95]. It is even hypothesized that such activation of the immune system may be beneficial and may induce a degree of tolerance. Manifestations of ACR include elevated levels of aminotransferase, alkaline phosphatase, bilirubin, and fever in later stages. Hepatic artery or portal vein thrombosis, biliary leak, CMV infection, and delayed graft function should be excluded. Diagnosis is finally confirmed by percutaneous liver biopsy prior to initiation of treatment, which depends on patient severity and current immunosuppression [94]. Cyclosporine is converted to tacrolimus or the sub-therapeutic levels of tacrolimus are increased and/or mycophenolate mofetil is added. In moderate to severe ACR, high doses of corticosteroids, usually methylprednizolone, are administered as a first-line medicine in a dose ranging from 500 to 1000 mg for 1–3 days depending on the center protocol [94].
