In Children With Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis Is Associated With Advanced Fibrosis

Nonalcoholic Steatohepatitis Clinical Research Network

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)438-446.e1
JournalClinical Gastroenterology and Hepatology
Volume16
Issue number3
DOIs
StatePublished - Mar 1 2018

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Fibrosis
Fatty Liver
Pediatrics
Non-alcoholic Fatty Liver Disease
Natural History
Research
Histology
Cross-Sectional Studies
Demography
Biopsy
Liver

Keywords

  • Disease Progression
  • NASH
  • Obesity
  • Pediatric

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

In Children With Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis Is Associated With Advanced Fibrosis. / Nonalcoholic Steatohepatitis Clinical Research Network.

In: Clinical Gastroenterology and Hepatology, Vol. 16, No. 3, 01.03.2018, p. 438-446.e1.

Research output: Contribution to journalArticle

Nonalcoholic Steatohepatitis Clinical Research Network. / In Children With Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis Is Associated With Advanced Fibrosis. In: Clinical Gastroenterology and Hepatology. 2018 ; Vol. 16, No. 3. pp. 438-446.e1.
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title = "In Children With Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis Is Associated With Advanced Fibrosis",
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.",
keywords = "Disease Progression, NASH, Obesity, Pediatric",
author = "{Nonalcoholic Steatohepatitis Clinical Research Network} and Africa, {Jonathan A.} and Behling, {Cynthia A.} and Brunt, {Elizabeth M.} and Nan Zhang and Yunjun Luo and Alan Wells and Jiayi Hou and Belt, {Patricia H.} and Rohit Kohil and Lavine, {Joel E.} and Molleston, {Jean P.} and Newton, {Kimberly P.} and Whitington, {Peter F.} and Schwimmer, {Jeffrey B.} and Abrams, {Stephanie H.} and Sarah Barlow and Ryan Himes and Rajesh Krisnamurthy and Leanel Maldonado and Rory Mahabir and April Carr and Kimberlee Bernstein and Kristin Bramlage and Kim Cecil and Stephanie DeVore and Rohit Kohli and Kathleen Lake and Daniel Podberesky and Alex Towbin and Stavra Xanthakos and Gerald Behr and Lefkowitch, {Jay H.} and Ali Mencin and Elena Reynoso and Adina Alazraki and Rebecca Cleeton and Maria Cordero and Albert Hernandez and Saul Karpen and Munos, {Jessica Cruz} and Nicholas Raviele and Miriam Vos and Molly Bozic and Cummings, {Oscar W.} and Ann Klipsch and Emily Ragozzino and Kumar Sandrasegaran and Girish Subbarao and Laura Walker and Ann Scheimann",
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T1 - In Children With Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis Is Associated With Advanced Fibrosis

AU - Nonalcoholic Steatohepatitis Clinical Research Network

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 - Abrams, Stephanie H.

AU - Barlow, Sarah

AU - Himes, Ryan

AU - Krisnamurthy, Rajesh

AU - Maldonado, Leanel

AU - Mahabir, Rory

AU - Carr, April

AU - Bernstein, Kimberlee

AU - Bramlage, Kristin

AU - Cecil, Kim

AU - DeVore, Stephanie

AU - Kohli, Rohit

AU - Lake, Kathleen

AU - Podberesky, Daniel

AU - Towbin, Alex

AU - Xanthakos, Stavra

AU - Behr, Gerald

AU - Lefkowitch, Jay H.

AU - Mencin, Ali

AU - Reynoso, Elena

AU - Alazraki, Adina

AU - Cleeton, Rebecca

AU - Cordero, Maria

AU - Hernandez, Albert

AU - Karpen, Saul

AU - Munos, Jessica Cruz

AU - Raviele, Nicholas

AU - Vos, Miriam

AU - Bozic, Molly

AU - Cummings, Oscar W.

AU - Klipsch, Ann

AU - Ragozzino, Emily

AU - Sandrasegaran, Kumar

AU - Subbarao, Girish

AU - Walker, Laura

AU - Scheimann, Ann

PY - 2018/3/1

Y1 - 2018/3/1

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.

AB - 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.

KW - Disease Progression

KW - NASH

KW - Obesity

KW - Pediatric

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JO - Clinical Gastroenterology and Hepatology

JF - Clinical Gastroenterology and Hepatology

SN - 1542-3565

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