Histopathology of De Novo Autoimmune Hepatitis in Children
A Manuyakorn, RS Venick, SV McDiarmid, CR Lassman. Siriraj Hospital, Bangkok, Thailand; UCLA, Los Angeles
Background: De novo autoimmune hepatitis (d-AIH) is a well-recognized complication of pediatric liver transplantation (LTx). The diagnosis is often based on elevated liver function tests (LFTs) and the presence of autoantibodies (a-Abs). The histology of d-AIH was first described in 1998. We present detailed histologic data from the largest series to date of biopsies in pediatric liver transplant patients with d-AIH.
Design: Between 1984 and 2008, 685 patients <18 y/o underwent 883 liver transplants (LTx). 70 recipients (10.2%) were identified as having developed d-AIH based on clinical parameters and biopsy. Liver biopsies obtained at or near the time of diagnosis were retrieved. Pathologic evaluation included scoring of interface, lobular and perivenular necroinflammatory activity, plasma cells density in each location, rejection activity index, apoptotic bodies, and fibrosis.
Results: Biopsies were available for re-review in 53 of 70 patients. Indication for LTx was biliary atresia (51%), fulminant hepatic failure (24%) and metabolic liver disease (15%). The mean time from LTx to development of d-AIH was 6.7 years. The majority of patients had strongly positive a-Ab titers and 43% had multiple positive a-Abs (ANA, dsDNA, SMA). 85% of patients had resolution of LFT abnormalities following treatment. In 38 biopsies (72%) the predominant pattern of injury was hepatitis. Pure lobular hepatitis was present in 7 (18%), pure interface hepatitis in 2 (5%), and pure perivenular hepatitis in only 1 (3%). Mixed interface/lobular hepatis was present in 8 (21%), mixed lobular/perivenular in 4 (11%), mixed interface/perivenular in 2 (5%) and mixed interface/lobular/perivenular in 14 (36%). Severe necroinflammatory activity was present in 7 (18%). In 7 biopsies (13%) convincing features of acute rejection in addition to hepatitis were present. In 2 (4%) there was ductopenia and in 5 (9%) there was minimal non-specific infiltrate. While perivenulitis was seen in 21 (40%), central vein endotheliitis was seen in only 3 (6%). Dense plasma cell infiltrates were seen in 30% of biopsies. 54% of patients had stage 2/4 or 3/4 fibrosis at presentation.
Conclusions: The dominant histologic pattern in biopsies of patients with a diagnosis of d-AIH is lobular hepatitis with or without interface and perivenular hepatitis. Plasma cell infiltrates were observed in all zones. Rejection histology was seen in only 13 % of cases. More than half of the patients had at least stage 2 fibrosis at presentation.
Category: Liver & Pancreas
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 149, Tuesday Morning