Chronic liver allograft rejection in a population treated primarily with tacrolimus as baseline immunosuppression - Long-term follow-up and evaluation of features for histopathological staging

Background, Predisposing factors, long-term occurrence, and histopathologic al changes associated with recovery or progression to allograft failure fro m chronic rejection (CR) were studied in adult patients treated primarily w ith tacrolimus. Methods. CR cases were identified using stringent criteria applied to a ret rospective review of computerized clinicopathological data and slides. Results, After 1973 days median follow-up, 35 (3.3%) of 1049 primary liver allograft recipients first developed CR between 16 and 2532 (median 242) da ys. The most significant risk factors for CR were the number (P<0.001) and histological severity (P<0.005) of acute rejection episodes and donor age > 40 years (P<0.03). Other demographic and matching parameters were not assoc iated with CR in this cohort, Ten patients died with, but not of, CR, Eight required retransplantation because of CR at a median of 268 days. Ten reso lved either histologically or by normalization of liver injury tests over a median of 548 days. CR persisted for 340 to 2116 days in the remaining sev en patients. More extensive bile duct loss (P<0.01), small arterial loss (P <0.03), foam cell clusters (P<0.01) and higher total bilirubin (P<0.02) and aspartate aminotransferase (P<0.03) were associated with allograft failure from CR. Conclusions. Early chronic liver allograft rejection is potentially reversi ble and a combination of histological, clinical, and laboratory data can be used to stage CR. Unique immunological and regenerative properties of live r allografts, which lead to a low incidence and reversibility of early CB, can provide insights into transplantation biology.