Prognostic implications of centrilobular necrosis in pediatric liver transplant recipients

We have observed centrilobular necrosis (CLN) in several liver allograft biopsies in our pediatric liver transplant population. The aims of this study were to describe the associated pathologic and clinical features of post-orthotopic liver transplantation CLN and determine its prognostic implications.

CLN was identified and characterized in 44 allografts from 40 patients (17 males and 23 females) among our 443 pediatric recipients. Twenty episodes were associated with cellular rejection, either in the same biopsy (n=15) or within the week prior (n=5), and five were associated with ductopenic rejection. Twelve were associated with vascular thrombosis. No clear etiology was identified in seven episodes, but two also had cholangitis lenta. Of the remaining five biopsies, three showed only centrilobular dropout, suggesting a resolution of some previous insult. The outcome of 40 patients following an initial episode of CLN was poor, with graft failure in 33, chronic poor function in 2, and normal recovery in only 5 patients. The results of retransplantation for graft failure due to CLN were equally poor, with 14 deaths, 3 patients with ductopenic rejection, and only 5 with normal recovery. CLN recurred in four grafts. Overall patient outcome was very poor: 25 deaths; 3 ductopenic rejections; 2 chronic poorly functioning livers; and 10 patients alive and well.

We conclude that CLN in pediatric orthotopic liver transplantation recipients is associated with cellular rejection, ductopenic rejection, or acute vessel thrombosis in the majority cases. The prognostic implications of CLN are grave, with high rates of graft failure requiring retransplantation and death.