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. 2017 Jul;65(1):89-92.
doi: 10.1097/MPG.0000000000001571.

Low Hepatic Tissue Copper in Pediatric Nonalcoholic Fatty Liver Disease

Michael Mendoza  1 , Shelley Caltharp, Ming Song, Lindsay Collin, Juna V Konomi, Craig J McClain, Miriam B Vos
Affiliations

Low Hepatic Tissue Copper in Pediatric Nonalcoholic Fatty Liver Disease

Michael Mendoza et al. J Pediatr Gastroenterol Nutr. 2017 Jul.

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.

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Conflict of interest statement

Conflicts of Interest/Financial Disclosure: Dr. Vos reports paid and unpaid consulting for pediatric NAFLD: Aegerion, Allegan, Intercept, Shire, Immuron and Target Pharmasolutions; and money or inkind research services: AMRA, Resonance Health and Target Pharmasolutions. All other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Comparison of mean hepatic copper (μg/g) in NAFLD (n=102) versus non-NAFLD (n=48). NAFLD subjects had lower mean tissue copper than non-NAFLD subjects (16.03 vs. 21.79, p=0.005).
Figure 2
Figure 2
Relationship between mean hepatic copper (μg/g) against severity of steatosis (n=150). Steatosis severity increases as hepatic copper decreases, p<0.001. Steatosis grade is based on criteria set by the NASH CRN, Grade 0: <5%, Grade 1: 5–33%, Grade 2: 34–66%, Grade 3: >66% steatosis.
See this image and copyright information in PMC

References

    1. Welsh JA, Karpen S, Vos MB. Increasing prevalence of nonalcoholic fatty liver disease among United States adolescents, 1988–1994 to 2007–2010. J Peds. 2013;162:496–500. - PMC - PubMed
    1. Zatulovskaia YA, Ilyechova EY, Puchkova LV. The Features of Copper Metabolism in the Rat Liver during Development. PLoS One. 2015;10:e0140797. - PMC - PubMed
    1. Tapiero H, Townsend DM, Tew KD. Trace elements in human physiology and pathology. Copper Biomed Pharmacother. 2003;57:386–98. - PMC - PubMed
    1. Hordyjewska A, Popiolek L, Kocot J. The many “faces” of copper in medicine and treatment. Biometals. 2014;27:611–21. - PMC - PubMed
    1. Rubino JT, Franz KJ. Coordination chemistry of copper proteins: how nature handles a toxic cargo for essential function. J Inorg Biochem. 2012;107:129–43. - PubMed