CENTRAL VENULITIS IN PEDIATRIC LIVER TRANSPLANTATION

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Alyssa M. Krasinskas, M.D.,1 Eduardo D. Ruchelli, M.D.,2 Elizabeth B. Rand, M.D.,3 Jesse L. Chittams, M.S.,4 Emma E. Furth, M.D.1

1Department of Anatomic Pathology and 4Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Medical Center, Philadelphia, PA. 2Department of Anatomic Pathology and 3Division of Pediatric Gastroenterology, Children's Hospital of Philadelphia, Philadelphia, PA.


Background: Central venulitis (CV), a distinct histologic lesion described in adult liver transplants, can occur with acute portal tract rejection or in isolation (isolated central venulitis, ICV). The etiology of ICV is uncertain: is it a result of immunosuppressive drug toxicity, acute cellular rejection, viral hepatitis or recurrent disease? Biopsy material and clinical data were collected on pediatric liver recipients to characterize CV in patients who generally do not develop viral hepatitis or recurrent disease.
Design: 45 of 59 children who received orthotopic liver transplants had 127 post-transplant liver biopsies available for review. Only four liver transplants were performed for potentially recurrent diseases (ie, primary sclerosing cholangitis) and none were performed for viral hepatitis. 44 of the 45 children received tacrolimus-based immunosuppression.
Results: ICV was identified in 12 of 127 post-transplant biopsies and in 7 of 45 allograft recipients. Acute portal tract rejection was first detected in allograft biopsies at a mean±SEM of 12.9±2.8 days post-transplantation, while ICV develop at 65.1±26.9 days. The finding of CV was not correlated with elevation of tacrolimus levels, reason for transplant, donor/recipient CMV status or blood type, cold ischemic times or the incidence of outflow obstruction. The responses of CV to therapy were variable and although the majority of cases resolved, several episodes persisted or recurred.
Conclusions: ICV occurred in 16% of pediatric post-transplant liver recipients and 9% of post-transplant liver biopsies. Since ICV was not associated with elevated tacrolimus levels, viral hepatitis or recurrent disease, since it developed later than acute portal-based rejection, and since it was responsive to anti-rejection therapy, ICV may be a variant of cellular rejection.


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