Cellular rejection is a common event in orthotopic liver transplantation, leading to significant morbidity and mortality. Late acute cellular rejection, which occurs at least 3 months post-transplant, affects 8-32% of pediatric liver transplant recipients. The histopathology and clinical outcome of patients affected by late cellular rejection are incompletely understood. The aims of this study were 1) to characterize late cellular rejection in the pediatric liver transplant population and describe the histopathology of late cellular rejection, with specific attention to centrilobular injury, including necrosis, inflammation, and endothelialitis and 2) to characterize the long-term outcome of pediatric liver transplant recipients with centrilobular injury, including necrosis, inflammation, and endothelialitis. All liver biopsies performed from August 1997 to August 2002 on pediatric patients at least 6 months post-transplant were reviewed, scored for rejection by Banff criteria and examined for centrilobular inflammatory changes. Histology was then correlated with clinical outcomes. Fifteen percent of biopsies had late cellular rejection by Banff criteria. Centrilobular inflammation, necrosis and central vein endothelialitis were common in these biopsies. In patients with similar centrilobular changes, but not meeting Banff criteria for rejection, 29% were treated for rejection and responded well clinically. The long-term outcome of patients with isolated centrilobular injury is similar to that of patients with centrilobular changes associated with portal based rejection. In conclusion, the presence of centrilobular inflammation, necrosis, or central vein endothelialitis should prompt consideration of late cellular rejection.
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