title: Nonalcoholic steatohepatitis in children: a multicenter clinicopathological study.
abstract: Nonalcoholic fatty liver disease (NAFLD) may have distinct histological features in children and adults, but to date limited data are available on the spectrum and significance of histological lesions in pediatric patients. We conducted a multicenter study of children with well-characterized, biopsy-proven NAFLD to (1) assess the presence and significance of a constellation of histological lesions and (2) identify clinical and laboratory predictors of disease severity. One hundred thirty children with NAFLD seen from 1995 to 2007 in five centers in the United States and Canada were studied. Clinical and laboratory data were collected. Slides stained with hematoxylin-eosin and trichrome were evaluated by two liver pathologists. The NAFLD activity score (NAS) and the pattern of liver injury (type 1 or adult versus type 2 or pediatric nonalcoholic steatohepatitis [NASH]) were recorded. Fibrosis was staged using a published 7-point scale. The median age was 12 years (range, 4-18 years); 63% were boys, and 52% were Caucasian. Fibrosis was present in 87% of patients; of these, stage 3 (bridging fibrosis) was present in 20%. No patient had cirrhosis. The median NAS was 4. Overlapping features of both type 1 (adult pattern) and type 2 (pediatric pattern) NASH were found in 82% of patients. Compared with patients with no or mild fibrosis, those with significant fibrosis were more likely to have higher lobular and portal inflammation scores (P < 0.01), perisinusoidal fibrosis (P < 0.001), and NAS > or =5 (P < 0.005). Serum aspartate aminotransferase levels were the only clinical or laboratory data that independently predicted severity of fibrosis (P = 0.003).
  
  
  CONCLUSIONS
  Our results highlight the limitations of published proposals to classify pediatric NAFLD, and identified histological lesions associated with progressive disease.
authors.affiliation: Department of Pediatric Gastroenterology and Nutrition, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Carter-Kent
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Yerian
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Brunt
authors.forename: Paul
authors.initials: P
authors.lastname: Angulo
authors.forename: Rohit
authors.initials: R
authors.lastname: Kohli
authors.forename: Simon C
authors.initials: SC
authors.lastname: Ling
authors.forename: Stavra A
authors.initials: SA
authors.lastname: Xanthakos
authors.forename: Peter F
authors.initials: PF
authors.lastname: Whitington
authors.forename: Phunchai
authors.initials: P
authors.lastname: Charatcharoenwitthaya
authors.forename: Jason
authors.initials: J
authors.lastname: Yap
authors.forename: Rocio
authors.initials: R
authors.lastname: Lopez
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: McCullough
authors.forename: Ariel E
authors.initials: AE
authors.lastname: Feldstein
mesh_terms: D000293:Adolescent; D001219:Aspartate Aminotransferases / Q000097:blood; D001706:Biopsy; D002170:Canada; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018450:Disease Progression; D005234:Fatty Liver / Q000097:blood / Q000175:diagnosis / Q000473:pathology*; D005260:Female; D006801:Humans; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000473:pathology; D008297:Male; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D012720:Severity of Illness Index; D014481:United States
chemical_list: D001219:Aspartate Aminotransferases