LATE ACUTE REJECTION OCCURRING IN LIVER ALLOGRAFT RECIPIENTS

To study the effect of immunosuppressive reduction on the incidence an d consequence of late acute rejection (LAR) in liver allograft recipie nts, mean daily prednisone dose, mean cyclosporine A (CsA) trough and nadir levels were retrospectively reviewed for the nearest 12-week per iod preceding six episodes of LAR in five liver allograft recipients ( group 1). Results were compared with those from a cohort of 12 liver a llograft recipients who did not develop LAR (group 2). LAR was defined as acute rejection occurring more than 365 days post-transplantation Median follow-up for both groups was similar (504 days, range 367 to 1 050, versus 511 days, range 365 to 666, not significant). Mean trough CsA levels were lower in patients with LAR compared with those without (224+/-66 ng/mL versus 233+/-49 ng/mL) but th e difference was not st atistically significant. In contrast, mean daily prednisone dose (2.5/-1.6 mg/day versus 6.5+/-2.9 mg/day P=0.007) and CsA nadir values (12 9+/-60 ng/mL versus 186+/-40 ng/mL, P=0.03) were significantly lower i n patients who developed LAR compared with those who did not. Five of six episodes (83%) of LAR occurred in patients receiving less than 5 m g/day of prednisone, versus a single LAR episode in only one of 12 pat ients (8%) receiving prednisone 5 mg/day or more (P=0.004). In all but one instance, LAR responded to pulse methylprednisolone without disce rnible affect of long term graft function. The authors conclude that l iver allograft recipients remain vulnerable to acute rejection beyond the first post-transplant year; and reduction of immunosuppressive the rapy, particularly prednisone, below a critical, albeit low dose, thre shold increases the risk of LAR.