{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T06:34:43Z","timestamp":1773815683417,"version":"3.50.1"},"reference-count":123,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Iuliu Ha\u021bieganu University of Medicine and Pharmacy","award":["771\/60\/11.01.2023"],"award-info":[{"award-number":["771\/60\/11.01.2023"]}]},{"name":"Iuliu Ha\u021bieganu University of Medicine and Pharmacy","award":["647\/53\/11.01.2024"],"award-info":[{"award-number":["647\/53\/11.01.2024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cholestasis in children is characterized by impaired bile flow that disrupts hepatic metabolism, nutrient homeostasis, and effects trace element balance. This narrative review summarizes current evidence on the metabolism, biological functions, and clinical implications of key trace elements\u2014zinc, selenium, copper, and manganese\u2014in pediatric cholestatic liver disease. The liver regulates trace element absorption, intracellular trafficking, storage, and biliary excretion; cholestasis alters these processes, leading to deficiencies or toxic accumulation. Zinc and selenium deficiencies are common and contribute to impaired growth, immune dysfunction, oxidative stress, and delayed hepatic regeneration. Conversely, reduced biliary excretion promotes copper and manganese accumulation, potentially exacerbating liver injury and causing manganese-related neurotoxicity. Recent advances in understanding metal-specific hepatic transporters and trafficking pathways have provided mechanistic insight into these alterations. Management strategies emphasize individualized supplementation, monitoring during enteral and parenteral nutrition, and prevention of deficiency and toxicity. Precision-based nutritional approaches may improve outcomes in pediatric cholestatic liver disease.<\/jats:p>","DOI":"10.3390\/ijms27062710","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T09:35:57Z","timestamp":1773740157000},"page":"2710","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dysregulation of Trace Elements in Pediatric Cholestasis: From Pathophysiology to Nutritional Approaches"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2074-0714","authenticated-orcid":false,"given":"Sorina","family":"Adam","sequence":"first","affiliation":[{"name":"\u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alina","family":"Grama","sequence":"additional","affiliation":[{"name":"2nd Pediatric Discipline, Department of Mother and Child, Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"},{"name":"2nd Pediatric Clinic, Emergency Clinical Hospital for Children, 400124 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0955-4486","authenticated-orcid":false,"given":"Alexandra","family":"Mititelu","sequence":"additional","affiliation":[{"name":"2nd Pediatric Discipline, Department of Mother and Child, Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"},{"name":"2nd Pediatric Clinic, Emergency Clinical Hospital for Children, 400124 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2099-8379","authenticated-orcid":false,"given":"Gabriel","family":"Ben\u0163a","sequence":"additional","affiliation":[{"name":"2nd Pediatric Discipline, Department of Mother and Child, Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"},{"name":"2nd Pediatric Clinic, Emergency Clinical Hospital for Children, 400124 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4931-1219","authenticated-orcid":false,"given":"Tudor Lucian","family":"Pop","sequence":"additional","affiliation":[{"name":"2nd Pediatric Discipline, Department of Mother and Child, Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"},{"name":"2nd Pediatric Clinic, Emergency Clinical Hospital for Children, 400124 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.jinorgbio.2019.03.013","article-title":"The Essential Metals for Humans: A Brief Overview","volume":"195","author":"Zoroddu","year":"2019","journal-title":"J. Inorg. Biochem."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Himoto, T., and Masaki, T. (2020). Current Trends of Essential Trace Elements in Patients with Chronic Liver Diseases. Nutrients, 12.","DOI":"10.3390\/nu12072084"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s42269-019-0166-y","article-title":"Zinc Status in Infants and Children with Cholestatic Liver Diseases and Its Effect on Growth","volume":"43","author":"Abdelhamid","year":"2019","journal-title":"Bull. Natl. Res. Cent."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1097\/MOG.0b013e328321b395","article-title":"Zinc Deficiency","volume":"25","author":"Tuerk","year":"2009","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1146\/annurev-nutr-033009-083312","article-title":"Mammalian Zinc Transporters: Nutritional and Physiologic Regulation","volume":"29","author":"Lichten","year":"2009","journal-title":"Annu. Rev. Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.clnesp.2024.04.007","article-title":"LLL 44-1 Micronutrients in Clinical Nutrition: Trace Elements","volume":"61","author":"Shenkin","year":"2024","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ullah, M.I., Alameen, A.A.M., Al-Oanzi, Z.H., Eltayeb, L.B., Atif, M., Munir, M.U., and Ejaz, H. (2023). Biological Role of Zinc in Liver Cirrhosis: An Updated Review. Biomedicines, 11.","DOI":"10.3390\/biomedicines11041094"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1016\/j.clnu.2022.02.015","article-title":"ESPEN Micronutrient Guideline","volume":"41","author":"Berger","year":"2022","journal-title":"Clin. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Himoto, T., and Masaki, T. (2018). Associations between Zinc Deficiency and Metabolic Abnormalities in Patients with Chronic Liver Disease. Nutrients, 10.","DOI":"10.3390\/nu10010088"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1177\/0884533611433534","article-title":"Zinc and Liver Disease","volume":"27","author":"Mohommad","year":"2012","journal-title":"Nutr. Clin. Pract."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7","DOI":"10.5604\/16652681.1184191","article-title":"The Role of Zinc in Liver Cirrhosis","volume":"15","author":"Reinhold","year":"2016","journal-title":"Ann. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1007\/s12011-017-1119-7","article-title":"Zinc Metabolism and Metallothioneins","volume":"183","author":"Baltaci","year":"2018","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kimura, T., and Kambe, T. (2016). The Functions of Metallothionein and ZIP and ZnT Transporters: An Overview and Perspective. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17030336"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1111\/jvh.12845","article-title":"The Antiviral Role of Zinc and Metallothioneins in Hepatitis C Infection","volume":"25","author":"Read","year":"2018","journal-title":"J. Viral Hepat."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1007\/s10930-017-9737-7","article-title":"Induction of Metallothionein in Rat Liver by Zinc Exposure: A Dose and Time Dependent Study","volume":"36","author":"Garla","year":"2017","journal-title":"Protein J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"100105","DOI":"10.1016\/j.metop.2021.100105","article-title":"The Role of Zinc in the Prevention and Treatment of Nonalcoholic Fatty Liver Disease","volume":"11","author":"Barbara","year":"2021","journal-title":"Metabol. Open"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.jaad.2013.04.028","article-title":"Zinc Deficiency and Its Management in the Pediatric Population: A Literature Review and Proposed Etiologic Classification","volume":"69","author":"Corbo","year":"2013","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"43","DOI":"10.4103\/prcm.prcm_4_25","article-title":"Zinc Deficiency in the Pediatric Population and Its Impact on Respiratory Health: A Review","volume":"9","author":"Wong","year":"2025","journal-title":"Pediatr. Respirol. Crit. Care Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1017\/S0954422421000342","article-title":"Dietary Zn Deficiency, the Current Situation and Potential Solutions","volume":"36","author":"Knez","year":"2023","journal-title":"Nutr. Res. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kare, A.P., Assefa, T., Desalegn, B.B., and Astatkie, A. (2025). Prevalence and Factors Associated with Zinc Deficiency among Preschool-Age Children in Rural Districts of Sidama Region, Ethiopia: A Community-Based Cross-Sectional Study. PLoS Glob. Public Health, 5.","DOI":"10.1371\/journal.pgph.0005356"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"73","DOI":"10.4103\/ejim.ejim_49_18","article-title":"Zinc Deficiency Correlates to Spontaneous Bacterial Peritonitis in Patients with Cirrhotic Ascites","volume":"31","author":"Hanna","year":"2019","journal-title":"Egypt. J. Intern. Med."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Gammoh, N.Z., and Rink, L. (2017). Zinc in Infection and Inflammation. Nutrients, 9.","DOI":"10.20944\/preprints201705.0176.v1"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4315140","DOI":"10.1155\/2018\/4315140","article-title":"Essential Role of Zinc and Zinc Transporters in Myeloid Cell Function and Host Defense against Infection","volume":"2018","author":"Sapkota","year":"2018","journal-title":"J. Immunol. Res."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Escobedo Monge, M.F., Barrado, E., Vicente, C.A., Redondo Del R\u00edo, M.P., and Marug\u00e1n de Miguelsanz, J.M. (2019). Zinc Nutritional Status in Patients with Cystic Fibrosis. Nutrients, 11.","DOI":"10.3390\/nu11010150"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1053\/j.gastro.2012.02.046","article-title":"The Zinc Transporter Zip14 Influences C-Met Phosphorylation and Hepatocyte Proliferation during Liver Regeneration in Mice","volume":"142","author":"Aydemir","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"602","DOI":"10.3390\/pediatric16030051","article-title":"Acquired and Inherited Zinc Deficiency-Related Diseases in Children: A Case Series and a Narrative Review","volume":"16","author":"Bellini","year":"2024","journal-title":"Pediatr. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1111\/j.1440-1746.2009.06003.x","article-title":"High Incidence of Zinc Deficiency among Filipino Children with Compensated and Decompensated Liver Disease","volume":"25","author":"Gregorio","year":"2010","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Lin, Y., He, F., Lian, S., Xie, B., Liu, T., He, J., and Liu, C. (2022). Selenium Status in Patients with Chronic Liver Disease: A Systematic Review and Meta-Analysis. Nutrients, 14.","DOI":"10.3390\/nu14050952"},{"key":"ref_29","first-page":"35","article-title":"Zinc Deficiency-Associated Dermatitis in Infants During a Nationwide Shortage of Injectable Zinc-Washington, DC, and Houston, Texas, 2012\u20132013","volume":"63","author":"Ruktanonchai","year":"2014","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1007\/s12263-014-0436-0","article-title":"Zinc Proteome Interaction Network as a Model to Identify Nutrient-Affected Pathways in Human Pathologies","volume":"9","author":"Leoni","year":"2014","journal-title":"Genes Nutr."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Dobrzy\u0144ska, M., Kaczmarek, K., Przys\u0142awski, J., and Drzyma\u0142a-Czy\u017c, S. (2023). Selenium in Infants and Preschool Children Nutrition: A Literature Review. Nutrients, 15.","DOI":"10.3390\/nu15214668"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/j.nut.2007.08.001","article-title":"Clinical Features of Selenium Deficiency in Infants Receiving Long-Term Nutritional Support","volume":"23","author":"Masumoto","year":"2007","journal-title":"Nutrition"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1111\/ppl.12144","article-title":"Dietary Mineral Supplies in Africa","volume":"151","author":"Joy","year":"2014","journal-title":"Physiol. Plant."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Awasthi, S., Kumar, D., Mahdi, A.A., Agarwal, G.G., Pandey, A.K., Parveen, H., Singh, S., Awasthi, R., Pande, H., and Anish, T.S. (2022). Prevalence of Specific Micronutrient Deficiencies in Urban School Going Children and Adolescence of India: A Multicenter Cross-Sectional Study. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0267003"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"E73","DOI":"10.1097\/MPG.0000000000003174","article-title":"Factors Affecting Selenium Status in Infants on Parenteral Nutrition Therapy","volume":"73","author":"Rao","year":"2021","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_36","first-page":"913","article-title":"Selenium in the Environment: Essential or Toxic to Human Health?","volume":"15","author":"Preda","year":"2016","journal-title":"Environ. Eng. Manag. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1089\/ars.2010.3275","article-title":"Selenium in human health and disease","volume":"14","author":"Bao","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3292","DOI":"10.3390\/molecules18033292","article-title":"Selenium in the Environment, Metabolism and Involvement in Body Functions","volume":"18","author":"Mehdi","year":"2013","journal-title":"Molecules"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1166\/jnn.2019.16287","article-title":"The Functions of Selenium and Selenoproteins Relating to the Liver Diseases","volume":"19","author":"Shang","year":"2018","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.bionut.2014.01.006","article-title":"Selenium Nutrition: How Important Is It?","volume":"4","author":"Priyadarsini","year":"2014","journal-title":"Biomed. Prev. Nutr."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Bai, S., Zhang, M., Tang, S., Li, M., Wu, R., Wan, S., Chen, L., Wei, X., and Feng, S. (2025). Effects and Impact of Selenium on Human Health, A Review. Molecules, 30.","DOI":"10.3390\/molecules30010050"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1042\/BJ20100368","article-title":"Selenium Compounds Are Substrates for Glutaredoxins: A Novel Pathway for Selenium Metabolism and a Potential Mechanism for Selenium-Mediated Cytotoxicity","volume":"429","author":"Wallenberg","year":"2010","journal-title":"Biochem. J."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Zhu, K., Yang, S., Li, T., Huang, X., Dong, Y., Wang, P., and Huang, J. (2022). Advances in the Study of the Mechanism by Which Selenium and Selenoproteins Boost Immunity to Prevent Food Allergies. Nutrients, 14.","DOI":"10.3390\/nu14153133"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Wang, F., Li, C., Li, S., Cui, L., Zhao, J., and Liao, L. (2023). Selenium and Thyroid Diseases. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1133000"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"952","DOI":"10.3803\/EnM.2021.1198","article-title":"Deiodinases and the Three Types of Thyroid Hormone Deiodination Reactions","volume":"36","author":"Sabatino","year":"2021","journal-title":"Endocrinol. Metab."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Sadler, R.A., Mallard, B.A., Shandilya, U.K., Hachemi, M.A., and Karrow, N.A. (2024). The Immunomodulatory Effects of Selenium: A Journey from the Environment to the Human Immune System. Nutrients, 16.","DOI":"10.3390\/nu16193324"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.neuro.2023.08.003","article-title":"Potential Role of Selenium in Modifying the Effect of Maternal Methylmercury Exposure on Child Neurodevelopment\u2014A Review","volume":"99","author":"Wesolowska","year":"2023","journal-title":"Neurotoxicology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1039\/C3MT00185G","article-title":"Selenium Biochemistry and Its Role for Human Health","volume":"6","author":"Roman","year":"2014","journal-title":"Metallomics"},{"key":"ref_49","first-page":"849","article-title":"Selenium in biology: Facts and medical perspectives","volume":"381","author":"Meyer","year":"2000","journal-title":"Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Saito, Y. (2021). Selenium Transport Mechanism via Selenoprotein P\u2014Its Physiological Role and Related Diseases. Front. Nutr., 8.","DOI":"10.3389\/fnut.2021.685517"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Liang, Q., Huang, R., Peng, Z., and Zou, M. (2024). Impact of Dietary Selenium and Blood Concentration on Liver Function: A Population-Based Study. Front. Nutr., 11.","DOI":"10.3389\/fnut.2024.1415288"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Batyrova, G., Taskozhina, G., Umarova, G., Umarov, Y., Morenko, M., Iriskulov, B., Kudabayeva, K., and Bazargaliyev, Y. (2025). Unveiling the Role of Selenium in Child Development: Impacts on Growth, Neurodevelopment and Immunity. J. Clin. Med., 14.","DOI":"10.3390\/jcm14041274"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s12937-016-0155-z","article-title":"Stunting, Selenium Deficiency and Anemia Are Associated with Poor Cognitive Performance in Preschool Children from Rural Ethiopia","volume":"15","author":"Gashu","year":"2016","journal-title":"Nutr. J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/s13312-025-00028-2","article-title":"Oral Selenium as an Adjunct in the Treatment of Acute Lower Respiratory Tract Infections in Children: A Double-Blind Randomized Controlled Trial","volume":"62","author":"Shaikh","year":"2025","journal-title":"Indian Pediatr."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.clnesp.2021.11.007","article-title":"Association of Selenium Status with Endothelial Activation during Acute Systemic Inflammation in Children","volume":"47","author":"Leite","year":"2022","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Genchi, G., Lauria, G., Catalano, A., Sinicropi, M.S., and Carocci, A. (2023). Biological Activity of Selenium and Its Impact on Human Health. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032633"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"S199","DOI":"10.1079\/BJN2001315","article-title":"Micronutrient Deficiency in Children","volume":"85","author":"Bhan","year":"2001","journal-title":"Br. J. Nutr."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"G\u00f6rlich, C.L., Sun, Q., Roggenkamp, V., Hackler, J., Mehl, S., Minich, W.B., Kaindl, A.M., and Schomburg, L. (2022). Selenium Status in Paediatric Patients with Neurodevelopmental Diseases. Nutrients, 14.","DOI":"10.3390\/nu14122375"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.freeradbiomed.2024.05.001","article-title":"Maternal Selenium Deficiency during Pregnancy in Association with Autism and ADHD Traits in Children: The Odense Child Cohort","volume":"220","author":"Demircan","year":"2024","journal-title":"Free Radic. Biol. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"352","DOI":"10.4103\/jiaps.JIAPS_143_19","article-title":"Evaluation of Serum Levels of Trace Elements in Children with Biliary Atresia and Their Correlation with Liver Histopathology","volume":"25","author":"Solanki","year":"2020","journal-title":"J. Indian Assoc. Pediatr. Surg."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"75","DOI":"10.2217\/14750708.6.1.75","article-title":"Management of Neonatal Cholestasis","volume":"6","author":"Best","year":"2009","journal-title":"Therapy"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1111\/apt.18179","article-title":"Prevalence and Prognostic Value of Zinc and Selenium Deficiency in Advanced Chronic Liver Disease","volume":"60","author":"Dominik","year":"2024","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_63","first-page":"642","article-title":"Copper Metabolism and Pediatric Cholestasis","volume":"14","author":"Corkins","year":"2011","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1111\/j.1753-4887.2009.00250.x","article-title":"New Developments in the Regulation of Intestinal Copper Absorptionn","volume":"67","author":"Klomp","year":"2009","journal-title":"Nutr. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1093\/jn\/134.5.1003","article-title":"Intracellular Copper Transport in Mammals 1,2","volume":"134","author":"Prohaska","year":"2004","journal-title":"J. Nutr."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1007\/s00424-020-02412-2","article-title":"The Molecular Mechanisms of Copper Metabolism and Its Roles in Human Diseases","volume":"472","author":"Chen","year":"2020","journal-title":"Pflug. Arch."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"13302","DOI":"10.1074\/jbc.M300034200","article-title":"The Role of the Invariant His-1069 in Folding and Function of the Wilson\u2019s Disease Protein, the Human Copper-Transporting ATPase ATP7B","volume":"278","author":"Tsivkovskii","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_68","unstructured":"National Research Council (2000). Copper in Drinking Water, National Academies Press."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/B978-0-12-821848-8.00183-9","article-title":"Copper","volume":"Volumes 1\u20134","author":"Aggett","year":"2023","journal-title":"Encyclopedia of Human Nutrition"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/0016-5085(78)90473-0","article-title":"Liver Copper Levels in Intrahepatic Cholestasis of Childhood","volume":"75","author":"Evans","year":"1978","journal-title":"Gastroenterology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1111\/his.13314","article-title":"Copper, Copper-Binding Protein and Cytokeratin 7 in Biliary Disorders","volume":"71","author":"Quaglia","year":"2017","journal-title":"Histopathology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ajg.2018.02.010","article-title":"Copper Concentrations in Egyptian Infants with Cholestasis: A Single Center Study","volume":"19","author":"Fouad","year":"2018","journal-title":"Arab J. Gastroenterol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1039\/c8mt00362a","article-title":"Body Distribution of Stable Copper Isotopes during the Progression of Cholestatic Liver Disease Induced by Common Bile Duct Ligation in Mice","volume":"11","author":"Hastuti","year":"2019","journal-title":"Metallomics"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0076-6879(90)86093-B","article-title":"Role of Free Radicals and Catalytic Metal Ions in Human Disease\u2014An Overview","volume":"186","author":"Halliwell","year":"1990","journal-title":"Methods Enzym."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/0014-5793(92)80911-Y","article-title":"Biologically Relevant Metal Ion-Dependent Hydroxyl Radical Generation An Update","volume":"307","author":"Halliwell","year":"1992","journal-title":"FEBS Lett."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1021\/acs.molpharmaceut.7b00841","article-title":"The Pivotal Role of Copper in Neurodegeneration: A New Strategy for the Therapy of Neurodegenerative Disorders","volume":"15","author":"Giampietro","year":"2018","journal-title":"Mol. Pharm."},{"key":"ref_77","first-page":"715","article-title":"The significance of variations in the distribution of copper in liver disease","volume":"99","author":"Goldfischer","year":"1980","journal-title":"Am. J. Pathol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1177\/0148607112443069","article-title":"Copper Levels in Cholestatic Infants on Parenteral Nutrition","volume":"37","author":"Corkins","year":"2013","journal-title":"J. Parenter. Enter. Nutr."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1002\/hep.22261","article-title":"Diagnosis and Treatment of Wilson Disease: An Update","volume":"47","author":"Roberts","year":"2008","journal-title":"Hepatology"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e477","DOI":"10.1016\/j.jns.2015.09.220","article-title":"Environmental Factors and Movement Disorders","volume":"357","author":"Youdim","year":"2015","journal-title":"J. Neurol. Sci."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Gollan, J.L., and Hewlett, A.T. (2012). Wilson Disease and Related Disorders. Handbook of Liver Disease, Elsevier Inc.","DOI":"10.1016\/B978-1-4377-1725-9.10017-6"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1620\/tjem.207.271","article-title":"Concentrations of Copper and Zinc in Liver and Serum Samples in Biliary Atresia Patients at Different Stages of Traditional Surgeries","volume":"207","author":"Sato","year":"2005","journal-title":"Tohoku J. Exp. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s12011-015-0237-3","article-title":"Study of Trace Elements in Liver Cirrhosis Patients and Their Role in Prognosis of Disease","volume":"165","author":"Nangliya","year":"2015","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.4254\/wjh.v13.i11.1552","article-title":"Chelation Therapy in Liver Diseases of Childhood: Current Status and Response","volume":"13","author":"Seetharaman","year":"2021","journal-title":"World J. Hepatol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.dld.2006.12.095","article-title":"Wilson Disease-A Practical Approach to Diagnosis, Treatment and Follow-Up","volume":"39","author":"Medici","year":"2007","journal-title":"Dig. Liver Dis."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"5451","DOI":"10.3748\/wjg.v23.i30.5451","article-title":"Wilson\u2019s Disease: Prospective Developments towards New Therapies","volume":"23","author":"Ranucci","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41572-018-0018-3","article-title":"Wilson Disease","volume":"4","author":"Litwin","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1111\/j.1365-2559.1981.tb01802.x","article-title":"Alpha-1-Antitrypsin and Copper in the Liver","volume":"5","author":"Callea","year":"1981","journal-title":"Histopathology"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/0016-5085(85)90326-9","article-title":"Abnormalities in Tests of Copper Metabolism in Primary Sclerosing Cholangitis","volume":"89","author":"Gross","year":"1985","journal-title":"Gastroenterology"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1136\/jcp.34.10.1071","article-title":"Is Copper Hepatotoxic in Primary Biliary Cirrhosis?","volume":"34","author":"Arborgh","year":"1981","journal-title":"J. Clin. Pathol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.yexcr.2008.10.022","article-title":"Niemann-Pick C1 Protein Transports Copper to the Secretory Compartment from Late Endosomes Where ATP7B Resides","volume":"315","author":"Yanagimoto","year":"2009","journal-title":"Exp. Cell Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1111\/j.1872-034X.2011.00788.x","article-title":"Copper Incorporation into Ceruloplasmin Is Regulated by Niemann-Pick C1 Protein","volume":"41","author":"Yanagimoto","year":"2011","journal-title":"Hepatol. Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1039\/C4MT00056K","article-title":"Hepatic Metabolic Response to Restricted Copper Intake in a Niemann-Pick C Murine Model","volume":"6","author":"Martinez","year":"2014","journal-title":"Metallomics"},{"key":"ref_94","unstructured":"Chen, P., Bornhorst, J., and Aschner, A.M. (2018). Manganese Metabolism in Humans, Universit\u00e4t Potsdam."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2","DOI":"10.4103\/ijpvm.IJPVM_48_19","article-title":"Trace Elements in Human Nutrition (II)\u2014An Update","volume":"11","author":"Mehri","year":"2020","journal-title":"Int. J. Prev. Med."},{"key":"ref_96","first-page":"199","article-title":"Manganese in Health and Disease","volume":"13","author":"Avila","year":"2013","journal-title":"Met. Ions Life Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1039\/C7MT00079K","article-title":"Influence of Iron Metabolism on Manganese Transport and Toxicity","volume":"9","author":"Ye","year":"2017","journal-title":"Metallomics"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Winslow, J.W.W., Limesand, K.H., and Zhao, N. (2020). The Functions of ZIP8, ZIP14, and ZnT10 in the Regulation of Systemic Manganese Homeostasis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21093304"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2332","DOI":"10.1016\/j.csbj.2023.03.039","article-title":"Recent Progress toward Understanding the Role of ZIP14 in Regulating Systemic Manganese Homeostasis","volume":"21","author":"McCabe","year":"2023","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1016\/B978-0-12-809954-4.00061-X","article-title":"Trace Metal Absorption and Transport","volume":"Volume 2","author":"Cousins","year":"2018","journal-title":"Physiology of the Gastrointestinal Tract"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.jphs.2021.10.011","article-title":"Manganese Transport in Mammals by Zinc Transporter Family Proteins, ZNT and ZIP","volume":"148","author":"Fujishiro","year":"2022","journal-title":"J. Pharmacol. Sci."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Pajarillo, E., Nyarko-Danquah, I., Digman, A., Multani, H.K., Kim, S., Gaspard, P., Aschner, M., and Lee, E. (2022). Mechanisms of Manganese-Induced Neurotoxicity and the Pursuit of Neurotherapeutic Strategies. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1011947"},{"key":"ref_103","first-page":"524","article-title":"The interpretation of trace element analysis in body fluids","volume":"128","author":"Guidotti","year":"2008","journal-title":"Indian J. Med. Res."},{"key":"ref_104","first-page":"475","article-title":"Recent Studies on Non-Invasive Biomarkers Useful in Biliary Atresia\u2014A Literature Review","volume":"70","year":"2023","journal-title":"Acta Biochim. Pol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/bs.ant.2020.11.003","article-title":"Neurotoxicity Mechanisms of Manganese in the Central Nervous System","volume":"Volume 5","author":"Pajarillo","year":"2021","journal-title":"Advances in Neurotoxicology"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1097\/MOP.0b013e32835e906b","article-title":"Manganese Exposure: Cognitive, Motor and Behavioral Effects on Children: A Review of Recent Findings","volume":"25","author":"Zoni","year":"2013","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/j.1651-2227.2001.tb01356.x","article-title":"Manganese intake and cholestatic jaundice in neonates receiving parenteral nutrition: A randomized controlled study","volume":"90","author":"Fok","year":"2001","journal-title":"Acta Paediatr."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Zemrani, B., McCallum, Z., and Bines, J.E. (2018). Trace Element Provision in Parenteral Nutrition in Children: One Size Does Not Fit All. Nutrients, 10.","DOI":"10.3390\/nu10111819"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2354","DOI":"10.1016\/j.clnu.2018.06.949","article-title":"ESPGHAN\/ESPEN\/ESPR\/CSPEN Guidelines on Pediatric Parenteral Nutrition: Iron and Trace Minerals","volume":"37","author":"Szitanyi","year":"2018","journal-title":"Clin. Nutr."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1177\/0884533612446706","article-title":"A.S.P.E.N. Position Paper: Recommendations for Changes in Commercially Available Parenteral Multivitamin and Multi-Trace Element Products","volume":"27","author":"Vanek","year":"2012","journal-title":"Nutr. Clin. Pract."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Mazzoni, B.P., Lessa, B.V., and Zamberlan, P. (2022). Metabolic and Nutritional Repercussions of Liver Disease on Children: How to Minimize Them?. Rev. Paul. Pediatr., 40.","DOI":"10.1590\/1984-0462\/2022\/40\/2020149"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1542\/pir.35.11.493","article-title":"Nutritional Considerations in Pediatric Liver Disease","volume":"35","author":"Cameron","year":"2014","journal-title":"Pediatr. Rev."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"3533","DOI":"10.1016\/j.clnu.2020.09.001","article-title":"ESPEN Practical Guideline: Clinical Nutrition in Liver Disease","volume":"39","author":"Bischoff","year":"2020","journal-title":"Clin. Nutr."},{"key":"ref_114","first-page":"OC25","article-title":"Correlation of Trace Elements in Patients of Chronic Liver Disease with Respect to Child- Turcotte-Pugh Scoring System","volume":"11","author":"Agarwal","year":"2017","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Taylor, A.J., Jones, L.J., and Osborn, D.A. (2017). Zinc Supplementation of Parenteral Nutrition in Newborn Infants. Cochrane Database Syst. Rev., 2017.","DOI":"10.1002\/14651858.CD012561"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1097\/MPG.0000000000003642","article-title":"Enteral Nutrition in Preterm Infants (2022): A Position Paper from the ESPGHAN Committee on Nutrition and Invited Experts","volume":"76","author":"Embleton","year":"2023","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"100295","DOI":"10.1016\/j.advnut.2024.100295","article-title":"Tracing Zinc\u2019s Role in Preterm Infants\u2019 Health: A Narrative Review","volume":"15","author":"Consales","year":"2024","journal-title":"Adv. Nutr."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"S61","DOI":"10.1053\/j.gastro.2009.07.071","article-title":"Selenium in Intravenous Nutrition","volume":"137","author":"Shenkin","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.jceh.2016.05.003","article-title":"Progressive Familial Intrahepatic Cholestasis (PFIC) in Indian Children: Clinical Spectrum and Outcome","volume":"6","author":"Agarwal","year":"2016","journal-title":"J. Clin. Exp. Hepatol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/S0946-672X(11)80007-6","article-title":"Hepatic Concentrations of Zinc, Copper and Manganese in Infants with Extrahepatic Biliary Atresia","volume":"9","author":"Bayliss","year":"1995","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.cca.2011.12.005","article-title":"Pediatric Reference Intervals for Serum Copper and Zinc","volume":"413","author":"Lin","year":"2012","journal-title":"Clin. Chim. Acta"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.envres.2013.05.006","article-title":"Relationship between Blood Manganese Levels and Children\u2019s Attention, Cognition, Behavior, and Academic Performance\u2014A Nationwide Cross-Sectional Study","volume":"126","author":"Bhang","year":"2013","journal-title":"Environ. Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1002\/lt.24640","article-title":"Biliary Atresia: Indications and Timing of Liver Transplantation and Optimization of Pretransplant Care","volume":"23","author":"Sundaram","year":"2017","journal-title":"Liver Transplant."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/6\/2710\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T05:38:48Z","timestamp":1773812328000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/6\/2710"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,16]]},"references-count":123,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ijms27062710"],"URL":"https:\/\/doi.org\/10.3390\/ijms27062710","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,16]]}}}