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

Jonathan A. Africa, Cynthia A. Behling, Elizabeth M. Brunt, Nan Zhang, Yunjun Luo, Alan Wells, Jiayi Hou, Patricia H. Belt, Rohit Kohil, Joel E. Lavine, Jean Molleston, Kimberly P. Newton, Peter F. Whitington, Girish Subbarao

Research output: Contribution to journalArticle

18 Citations (Scopus)

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)
JournalClinical Gastroenterology and Hepatology
DOIs
StateAccepted/In press - 2017

Fingerprint

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. / Africa, Jonathan A.; Behling, Cynthia A.; Brunt, Elizabeth M.; Zhang, Nan; Luo, Yunjun; Wells, Alan; Hou, Jiayi; Belt, Patricia H.; Kohil, Rohit; Lavine, Joel E.; Molleston, Jean; Newton, Kimberly P.; Whitington, Peter F.; Subbarao, Girish.

In: Clinical Gastroenterology and Hepatology, 2017.

Research output: Contribution to journalArticle

Africa, JA, Behling, CA, Brunt, EM, Zhang, N, Luo, Y, Wells, A, Hou, J, Belt, PH, Kohil, R, Lavine, JE, Molleston, J, Newton, KP, Whitington, PF & Subbarao, G 2017, 'In Children With Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis Is Associated With Advanced Fibrosis', Clinical Gastroenterology and Hepatology. https://doi.org/10.1016/j.cgh.2017.02.030
Africa, Jonathan A. ; Behling, Cynthia A. ; Brunt, Elizabeth M. ; Zhang, Nan ; Luo, Yunjun ; Wells, Alan ; Hou, Jiayi ; Belt, Patricia H. ; Kohil, Rohit ; Lavine, Joel E. ; Molleston, Jean ; Newton, Kimberly P. ; Whitington, Peter F. ; Subbarao, Girish. / In Children With Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis Is Associated With Advanced Fibrosis. In: Clinical Gastroenterology and Hepatology. 2017.
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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.",
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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

AU - Newton, Kimberly P.

AU - Whitington, Peter F.

AU - Subbarao, Girish

PY - 2017

Y1 - 2017

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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