title: In Children With Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis Is Associated With Advanced Fibrosis.
abstract: Focal zone 1 steatosis, although rare in adults with nonalcoholic fatty liver disease (NAFLD), does occur in children with NAFLD. We investigated whether focal zone 1 steatosis and focal zone 3 steatosis are distinct subphenotypes of pediatric NAFLD. We aimed to determine associations between the zonality of steatosis and demographic, clinical, and histologic features in children with NAFLD.
  
  
  
  We performed a cross-sectional study of baseline data from 813 children (age <18 years; mean age, 12.8 ± 2.7 years). The subjects had biopsy-proven NAFLD and were enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network. Liver histology was reviewed using the Nonalcoholic Steatohepatitis Clinical Research Network scoring system.
  
  
  
  Zone 1 steatosis was present in 18% of children with NAFLD (n = 146) and zone 3 steatosis was present in 32% (n = 244). Children with zone 1 steatosis were significantly younger (10 vs 14 years; P < .001) and a significantly higher proportion had any fibrosis (81% vs 51%; P < .001) or advanced fibrosis (13% vs 5%; P < .001) compared with children with zone 3 steatosis. In contrast, children with zone 3 steatosis were significantly more likely to have steatohepatitis (30% vs 6% in children with zone 1 steatosis; P < .001).
  
  
  
  Children with zone 1 or zone 3 distribution of steatosis have an important subphenotype of pediatric NAFLD. Children with zone 1 steatosis are more likely to have advanced fibrosis and children with zone 3 steatosis are more likely to have steatohepatitis. To achieve a comprehensive understanding of pediatric NAFLD, studies of pathophysiology, natural history, and response to treatment should account for the zonality of steatosis.
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla, California; Department of Gastroenterology, Rady Children's Hospital San Diego, San Diego, California.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Africa
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla, California; Department of Pathology, Sharp Memorial Hospital, San Diego, California.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Behling
authors.affiliation: Department of Pathology, Washington University, St. Louis, Missouri.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Brunt
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla, California.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla, California.
authors.forename: Yunjun
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Clinical and Translational Research Institute, University of California San Diego School of Medicine, La Jolla, California.
authors.forename: Alan
authors.initials: A
authors.lastname: Wells
authors.affiliation: Clinical and Translational Research Institute, University of California San Diego School of Medicine, La Jolla, California.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Hou
authors.affiliation: Johns Hopkins University, Baltimore, Maryland.
authors.forename: Patricia H
authors.initials: PH
authors.lastname: Belt
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Rohit
authors.initials: R
authors.lastname: Kohil
authors.affiliation: Department of Pediatrics, Columbia University, New York, New York.
authors.forename: Joel E
authors.initials: JE
authors.lastname: Lavine
authors.affiliation: Department of Pediatrics, Indiana University, Indianapolis, Indiana; James Whitcomb Riley Hospital, Indianapolis, Indiana.
authors.forename: Jean P
authors.initials: JP
authors.lastname: Molleston
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla, California; Department of Gastroenterology, Rady Children's Hospital San Diego, San Diego, California.
authors.forename: Kimberly P
authors.initials: KP
authors.lastname: Newton
authors.affiliation: Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Whitington
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla, California; Department of Gastroenterology, Rady Children's Hospital San Diego, San Diego, California. Electronic address: jschwimmer@ucsd.edu.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Schwimmer
mesh_terms: D000293:Adolescent; D001706:Biopsy; D002648:Child; D003430:Cross-Sectional Studies; D005234:Fatty Liver / Q000209:etiology* / Q000473:pathology*; D005260:Female; D006526:Hepatitis C; D006651:Histocytochemistry; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications* / Q000473:pathology*; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications*
keywords: Disease Progression; NASH; Obesity; Pediatric