studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 1051A
1728
Serum autoantibodies are associated with chronic hepatitis
and graft fibrosis after pediatric liver transplantation
Jeremy K. Rajanayagam 1 , Wolfram Haller 1 , Dominique Debray 2 ,
Henkjan J. Verkade 3 , Valerie A. McLin 4 , Helen M. Evans 5 , Etienne
M. Sokal 6 , Ekkehard Sturm 7 , Rene Scheenstra 3 , Annette S. Gouw 8 ,
Vladimir Cousin 4 , Sharat Varma 9 , Steffen Hartleif 7 , James Hodson
10 , Deirdre A. Kelly 1 ; 1 The Liver Unit, BIrmingham Children’s
Hospital, Birmingham, United Kingdom; 2 Clinique chirurgicale
Infantile, Necker Hospital, Paris, France; 3 Paediatric Hepatology,
Beatrix Children’s Hospital, University Medical Center Groningen,
Groningen, Netherlands; 4 Paediatrics, University Hospitals
Geneva, Geneva, Switzerland; 5 Hepatology, Starship Children’s
Hospital, Auckland, New Zealand; 6 Paediatric Hepatology and
Cell Therapy Lab, Université Catholique de Louvain, Louvain,
Belgium; 7 Paediatric Gastroenterology & Hepatology, University
Children’s Hospital, Tuebingen, Germany; 8 Pathology and Medical
Biology, University Medical Center Groningen, Groningen,
Netherlands; 9 Cliniques universitaires St Luc, Brussels, Belgium;
10 University Hospitals Birmingham, Birmingham, United Kingdom
Background: Chronic hepatitis (CH) and fibrosis are frequent
features of protocol liver biopsies after pediatric liver transplantation
(LT). Previously reported associations with positive autoantibodies
(AuAb) and abnormal immunoglobulins (Ig) suggest
immunologic mechanisms of graft injury. Aim: To evaluate the
role of AuAbs and Igs in the etiology of CH and fibrosis. Methods:
International, multicenter, retrospective analysis of pediatric
LT recipients with 5 and/or 10 yr protocol liver biopsies
(normal aminotransaminases), paired serum AuAbs (ANA or
SMA titre>1:40) and Ig levels, excluding those with pre-LT autoimmune
liver disease, or other causes of graft injury. Results:
467 children, from 7 centres underwent LT between 1985-
2010, predominantly for biliary atresia (n=274), metabolic
disease (n=58), other cholestatic disorders (n=53), acute liver
failure (n=44), cryptogenic cirrhosis (n=20) and malignancy
(n=7). CH was seen in 119/279 (43%) biopsies at 5yrs,
and 121/229 (53%) biopsies at 10yrs. Fibrosis was present
in 163/301 (54%) at 5yrs (mild=36%; moderate=12%;
severe=6%) and 178/226 (79%) at 10yrs (mild=46%;, moderate=20%;
and severe=13%). Children positive vs negative
for AuAbs were more likely to exhibit not only CH (5yrs: 59%
vs 34%, p