Hepatic Dry Copper Weight in Pediatric Autoimmune Liver Disease.
Journal
Journal of pediatric gastroenterology and nutrition
ISSN: 1536-4801
Titre abrégé: J Pediatr Gastroenterol Nutr
Pays: United States
ID NLM: 8211545
Informations de publication
Date de publication:
01 02 2023
01 02 2023
Historique:
pubmed:
5
11
2022
medline:
1
2
2023
entrez:
4
11
2022
Statut:
ppublish
Résumé
Elevated hepatic dry copper weight is recognized in adults with autoimmune liver disease (AILD) and chronic cholestasis. We aim to review hepatic dry copper weight in pediatric AILD. Retrospective review of pediatric AILD managed at our institution from 1999 to 2018, and 104 patients with hepatic dry copper weight assessment were included. Median age at presentation was 13.4 years (interquartile range, IQR, 11.7-14.9), 60% female, 54% autoimmune hepatitis, 42% autoimmune sclerosing cholangitis, and 4% primary sclerosing cholangitis. Histological features of advanced liver fibrosis in 68%. Median hepatic dry copper weight was 51.1 µg/g dry weight (IQR, 28.0-103.8). Elevated hepatic dry copper weight (>50 µg/g dry weight) was present in 51%, and was not associated with AILD subtype ( P = 0.83), age at presentation ( P = 0.68), or advanced fibrosis ( P = 0.53). Liver transplantation (LT) was performed in 10%, who had higher hepatic dry copper weight (148.5 µg/g dry weight [IQR, 39.5-257.3] vs 47.5 [IQR, 27.8-91.5], P = 0.04); however this was not associated with LT on multivariate analysis (hazard ratio 1.002, 95% CI 0.999-1.005, P = 0.23). In 8 (7.7%) patients ATP7B was sequenced and potentially disease causing variants were identified in 2 patients, both who required LT. Elevations in hepatic dry copper weight are common in pediatric AILD. Unlike in adults, it is not associated with AILD subtypes with cholestasis. Higher dry copper weight was detected in patients who required LT. While further work is needed to identify the significance of copper deposition in pediatric AILD, we recommend close monitoring of patients with elevated levels for progressive liver disease.
Identifiants
pubmed: 36332083
doi: 10.1097/MPG.0000000000003654
pii: 00005176-202302000-00008
doi:
Substances chimiques
Copper
789U1901C5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e21-e26Informations de copyright
Copyright © 2022 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest.
Références
Mieli-Vergani G, Vergani D, Baumann U, et al. Diagnosis and management of pediatric autoimmune liver disease: ESPGHAN Hepatology Committee Position Statement. J Pediatr Gastroenterol Nutr. 2018;66:345–60.
Roberts EA, Schilsky ML, American Association for Study of Liver Diseases (AASLD). Diagnosis and treatment of Wilson disease: an update. Hepatology. 2008;47:2089–111.
European Association for the Study of the Liver. EASL clinical practice guidelines: Wilson’s disease. J Hepatol. 2012;56:671–85.
Socha P, Janczyk W, Dhawan A, et al. Wilson’s disease in children: a position paper by the Hepatology Committee of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2018;66:334–44.
Smallwood RA, Williams HA, Rosenoer VM, et al. Liver-copper levels in liver disease: studies using neutron activation analysis. Lancet. 1968;292:1310–3.
Kowdley KV, Knox TA, Kaplan MM. Hepatic copper content is normal in early primary biliary cirrhosis and primary sclerosing cholangitis. Dig Dis Sci. 1994;39:2416–20.
Gross Jr JB, Ludwig J, Wiesner RH, McCall JT, LaRusso NF. Abnormalities in tests of copper metabolism in primary sclerosing cholangitis. Gastroenterology. 1985;89:272–8.
Yang X, Tang XP, Zhang YH, et al. Prospective evaluation of the diagnostic accuracy of hepatic copper content, as determined using the entire core of a liver biopsy sample. Hepatology. 2015;62:1731–41.
Wiesner RH, LaRusso NF. Clinicopathologic features of the syndrome of primary sclerosing cholangitis. Gastroenterology. 1980;79:200–6.
Gregorio GV, Portmann B, Karani J, et al. Autoimmune hepatitis/sclerosing cholangitis overlap syndrome in childhood: a 16-year prospective study. Hepatology. 2001;33:544–53.
Ludwig J, Barham SS, Larusso NF, Elveback LR, Wiesner RH, McCall JT. Morphologic features of chronic hepatitis associated with primary sclerosing cholangitis and chronic ulcerative colitis. Hepatology. 1981;1:632–40.
Aaseth J, Thomassen Y, Aadland E, Fausa O, Schrumpf E. Hepatic retention of copper and selenium in primary sclerosing cholangitis. Scand J Gastroenterol. 1995;30:1200–3.
Mounajjed T, Oxentenko AS, Qureshi H, Smyrk TC. Revisiting the topic of histochemically detectable copper in various liver diseases with special focus on venous outflow impairment. Am J Clin Pathol. 2013;139:79–86.
Sipponen P, Salaspuro MP, Makkonen HM. Orcein positive hepatocellular material in histological diagnosis of primary biliary cirrhosis. Ann Clin Res. 1975;7:273–7.
Jain S, Scheuer PJ, Archer BA, Newman SP, Sherlock S. Histological demonstration of copper and copper-associated protein in chronic liver diseases. J Clin Pathol. 1978;31:784–90.
Deneau MR, El-Matary W, Valentino PL, et al. The natural history of primary sclerosing cholangitis in 781 children: a multicenter, international collaboration. Hepatology. 2017;66:518–27.
Shneider BL. ABCB4 disease presenting with cirrhosis and copper overload-potential confusion with Wilson disease. J Clin Exp Hepatol. 2011;1:115–7.
Stättermayer AF, Halilbasic E, Wrba F, Ferenci P, Trauner M. Variants in ABCB4 (MDR3) across the spectrum of cholestatic liver diseases in adults. J Hepatol. 2020;73:651–63.
Sticova E, Neroldova M, Kotalova R, Subhanova I, Jirsa M. ABCB4 disease mimicking morbus Wilson: a potential diagnostic pitfall. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2020;164:121–5.
Nayagam JS, Williamson C, Joshi D, Thompson RJ. Liver disease in adults with variants in the cholestasis-related genes ABCB11, ABCB4 and ATP8B1. Aliment Pharmacol Ther. 2020;52:1628–39.
Karlsen TH, Chung BK. Genetic risk and the development of autoimmune liver disease. Dig Dis. 2015;33:13–24.
Sintusek P, Dhawan A. Liver copper estimation: does liver biopsy size really matter? Hepatology. 2016;64:1381–2.