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

• DOI: 10.1016/j.cgh.2017.02.030
• Publication Date: 2017-03-07T20:01:02Z
• Authors: 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 P. Molleston; Kimberly P. Newton; Peter F. Whitington; Jeffrey B. Schwimmer; Stephanie H. Abrams; Sarah Barlow; Ryan Himes; Rajesh Krisnamurthy; Leanel Maldonado; Rory Mahabir; April Carr; Kimberlee Bernstein; Kristin Bramlage; Kim Cecil; Stephanie DeVore; Rohit Kohli; Kathleen Lake; Daniel Podberesky; Alex Towbin; Stavra Xanthakos; Gerald Behr; Joel E. Lavine; Jay H. Lefkowitch; Ali Mencin; Elena Reynoso; Adina Alazraki; Rebecca Cleeton; Maria Cordero; Albert Hernandez; Saul Karpen; Jessica Cruz Munos; Nicholas Raviele; Miriam Vos; Molly Bozic; Oscar W. Cummings; Ann Klipsch; Jean P. Molleston; Emily Ragozzino; Kumar Sandrasegaran; Girish Subbarao; Laura Walker; Kimberly Kafka; Ann Scheimann; Joy Ito; Mark H. Fishbein; Saeed Mohammad; Cynthia Rigsby; Lisa Sharda; Peter F. Whitington; Sarah Barlow; Theresa Cattoor; Jose Derdoy; Janet Freebersyser; Ajay Jain; Debra King; Jinping Lai; Pat Osmack; Joan Siegner; Susan Stewart; Susan Torretta; Kristina Wriston; Susan S. Baker; Diana Lopez–Graham; Sonja Williams; Lixin Zhu; Jonathan Africa; Hannah Awai; Cynthia Behling; Craig Bross; Jennifer Collins; Janis Durelle; Kathryn Harlow; Michael Middleton; Kimberly Newton; Melissa Paiz; Jeffrey B. Schwimmer; Claude Sirlin; Patricia Ugalde-N...; Mariana Dominguez...; Bradley Aouizerat; Jesse Courtier; Linda D. Ferrell; Natasha Feier; Ryan Gill; Camille Langlois; Emily Rothbaum Pe...; Philip Rosenthal; Patrika Tsai; Kara Cooper; Simon Horslen; Evelyn Hsu; Karen Murray; Randolph Otto; Matthew Yeh; Melissa Young; Elizabeth M. Brunt; Kathryn Fowler
• Keywords: Liver Cirrhosis; Male; Adolescent; Biopsy; Clinical Sciences; Chronic Liver Disease and Cirrhosis; Hepatitis; disease progression; Clinical Research; Non-alcoholic Fatty Liver Disease; 616; Humans; Obesity; 14. Life underwater; Child; Pediatric; Biomedical and Clinical Sciences; Gastroenterology & Hepatology; Histocytochemistry; Liver Disease; NASH; 15. Life on land; Hepatitis C; 3. Good health; Fatty Liver; pediatric; Good Health and Well Being; Cross-Sectional Studies; Disease Progression; Nonalcoholic Steatohepatitis Clinical Research Network; Female; Digestive Diseases

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.