Low Hepatic Tissue Copper in Pediatric Nonalcoholic Fatty Liver Disease.

• Type of Material: Article
• Authors: Michael Mendoza, University of Louisville School of Medicine; Shelley A. Caltharp, Emory University; Ming Song, Emory University; Lindsay Collin, Emory University; Juna V. Konomi, Emory University; Craig J McClain, University of Louisville School of Medicine; Miriam Benedicta Vos, Emory University
• Language: English
• Date: 2017-07-01
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: Copyright © ESPGHAN and NASPGHAN. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1097/MPG.0000000000001571
• Title of Journal or Parent Work: Journal of Pediatric Gastroenterology and Nutrition
• ISSN: 0277-2116
• Volume: 65
• Issue: 1
• Start Page: 89
• End Page: 92
• Grant/Funding Information: The study was funded, in part, from grants from the National Institutes of NIH R03 DK096157 (MBV) and NIH K23 DK080953-05 (MBV).
• Keywords: Liver; Trace Elements; Humans; Child, Preschool; Copper; Biomarkers; Young Adult; Retrospective Studies; Male; Child; Female; Adolescent; Case-Control Studies; Non-alcoholic Fatty Liver Disease; Severity of Illness Index
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

OBJECTIVE: Animal models and studies in adults have demonstrated that copper restriction increases severity of liver injury in nonalcoholic fatty liver disease (NAFLD). This has not been studied in children. We aimed to determine if lower tissue copper is associated with increased NAFLD severity in children. METHODS: This was a retrospective study of pediatric patients who had a liver biopsy including a hepatic copper quantitation. The primary outcome compared hepatic copper concentration in NAFLD versus non-NAFLD. Secondary outcomes compared hepatic copper levels against steatosis, fibrosis, lobular inflammation, balloon degeneration, and NAFLD activity score (NAS). RESULTS: The study analysis included 150 pediatric subjects (102 with NAFLD and 48 non-NAFLD). After adjusting for age, body mass index z score, gamma glutamyl transferase, alanine aminotransferase, and total bilirubin, NAFLD subjects had lower levels of hepatic copper than non-NAFLD (P = 0.005). In addition, tissue copper concentration decreased as steatosis severity increased (P < 0.001). Copper levels were not associated with degree of fibrosis, lobular inflammation, portal inflammation, or balloon degeneration. CONCLUSIONS: In this cohort of pediatric subjects with NAFLD, we observed decreased tissue copper levels in subjects with NAFLD when compared with non-NAFLD subjects. In addition, tissue copper levels were lower in subjects with nonalcoholic steatohepatitis, a more severe form of the disease, when compared with steatosis alone. Further studies are needed to explore the relationship between copper levels and NAFLD progression.