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In Children With Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis Is Associated With Advanced Fibrosis.
Clin Gastroenterol Hepatol. 2018 03; 16(3):438-446.e1.CG

Abstract

BACKGROUND & AIMS

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.

METHODS

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.

RESULTS

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).

CONCLUSIONS

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+Show Affiliations

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.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.Department of Pathology, Washington University, St. Louis, Missouri.Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla, California.Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla, California.Clinical and Translational Research Institute, University of California San Diego School of Medicine, La Jolla, California.Clinical and Translational Research Institute, University of California San Diego School of Medicine, La Jolla, California.Johns Hopkins University, Baltimore, Maryland.Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.Department of Pediatrics, Columbia University, New York, New York.Department of Pediatrics, Indiana University, Indianapolis, Indiana; James Whitcomb Riley Hospital, Indianapolis, Indiana.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.Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.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.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

28286193

Citation

Africa, Jonathan A., et al. "In Children With Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis Is Associated With Advanced Fibrosis." Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association, vol. 16, no. 3, 2018, pp. 438-446.e1.
Africa JA, Behling CA, Brunt EM, et al. In Children With Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis Is Associated With Advanced Fibrosis. Clin Gastroenterol Hepatol. 2018;16(3):438-446.e1.
Africa, J. A., Behling, C. A., Brunt, E. M., Zhang, N., Luo, Y., Wells, A., Hou, J., Belt, P. H., Kohil, R., Lavine, J. E., Molleston, J. P., Newton, K. P., Whitington, P. F., & Schwimmer, J. B. (2018). In Children With Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis Is Associated With Advanced Fibrosis. Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association, 16(3), 438-e1. https://doi.org/10.1016/j.cgh.2017.02.030
Africa JA, et al. In Children With Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis Is Associated With Advanced Fibrosis. Clin Gastroenterol Hepatol. 2018;16(3):438-446.e1. PubMed PMID: 28286193.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In Children With Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis Is Associated With Advanced Fibrosis. AU - Africa,Jonathan A, AU - Behling,Cynthia A, AU - Brunt,Elizabeth M, AU - Zhang,Nan, AU - Luo,Yunjun, AU - Wells,Alan, AU - Hou,Jiayi, AU - Belt,Patricia H, AU - Kohil,Rohit, AU - Lavine,Joel E, AU - Molleston,Jean P, AU - Newton,Kimberly P, AU - Whitington,Peter F, AU - Schwimmer,Jeffrey B, AU - ,, Y1 - 2017/03/07/ PY - 2016/09/08/received PY - 2017/01/26/revised PY - 2017/02/14/accepted PY - 2017/3/14/pubmed PY - 2019/11/7/medline PY - 2017/3/14/entrez KW - Disease Progression KW - NASH KW - Obesity KW - Pediatric SP - 438 EP - 446.e1 JF - Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association JO - Clin. Gastroenterol. Hepatol. VL - 16 IS - 3 N2 - BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. SN - 1542-7714 UR - https://www.unboundmedicine.com/medline/citation/28286193/In_Children_With_Nonalcoholic_Fatty_Liver_Disease_Zone_1_Steatosis_Is_Associated_With_Advanced_Fibrosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1542-3565(17)30261-6 DB - PRIME DP - Unbound Medicine ER -