{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T11:48:10Z","timestamp":1791373690512,"version":"4.3.1"},"reference-count":133,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T00:00:00Z","timestamp":1636502400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Decompensated liver cirrhosis has a dismal prognosis, with patients surviving on average for 2\u20134 years after the first diagnosis of ascites. Albumin is an important tool in the therapy of cirrhotic ascites. By virtue of its oncotic properties, it reduces the risk of cardiovascular dysfunction after paracentesis. Treatment with albumin also counteracts the development of hepatorenal syndrome and spontaneous bacterial peritonitis. More recently, the positive impact of long-term albumin supplementation in liver disease, based on its pleiotropic non-oncotic activities, has been recognized. These include transport of endo- and exogenous substances, anti-inflammatory, antioxidant and immunomodulatory activities, and stabilizing effects on the endothelium. Besides the growing recognition that effective albumin therapy requires adjustment of the plasma level to normal physiological values, the search for substances with adjuvant activities is becoming increasingly important. More than 75% of patients with decompensated liver cirrhosis do not only present with hypoalbuminemia but also with zinc deficiency. There is a close relationship between albumin and the essential trace element zinc. First and foremost, albumin is the main carrier of zinc in plasma, and is hence critical for systemic distribution of zinc. In this review, we discuss important functions of albumin in the context of metabolic, immunological, oxidative, transport, and distribution processes, alongside crucial functions and effects of zinc and their mutual dependencies. In particular, we focus on the major role of chronic inflammatory processes in pathogenesis and progression of liver cirrhosis and how albumin therapy and zinc supplementation may affect these processes.<\/jats:p>","DOI":"10.3390\/nu13114011","type":"journal-article","created":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T23:04:46Z","timestamp":1636671886000},"page":"4011","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Albumin Substitution in Decompensated Liver Cirrhosis: Don\u2019t Forget Zinc"],"prefix":"10.3390","volume":"13","author":[{"given":"Kurt","family":"Gr\u00fcngreiff","sequence":"first","affiliation":[{"name":"Clinic of Gastroenterology, City Hospital Magdeburg GmbH, 39130 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Gottstein","sequence":"additional","affiliation":[{"name":"Clinic of Gastroenterology, City Hospital Magdeburg GmbH, 39130 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6441-9631","authenticated-orcid":false,"given":"Dirk","family":"Reinhold","sequence":"additional","affiliation":[{"name":"Medical Faculty, Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8396-9332","authenticated-orcid":false,"given":"Claudia A.","family":"Blindauer","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1002\/hep.26338","article-title":"Albumin: Pathophysiologic basis of its role in the treatment of cirrhosis and its complications","volume":"58","author":"Caraceni","year":"2013","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"547","DOI":"10.5604\/01.3001.0012.0916","article-title":"New insights about albumin and liver disease","volume":"17","author":"Carvalho","year":"2018","journal-title":"Ann. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1002\/hep.27322","article-title":"Posttranscriptional changes of serum albumin: Clinical and prognostic significance in hospitalized patients with cirrhosis","volume":"60","author":"Domenicali","year":"2014","journal-title":"Hepatology"},{"key":"ref_4","first-page":"83","article-title":"(D)ILC\u2013Entwicklungen in der Hepatologie","volume":"58","author":"Sauerbruch","year":"2020","journal-title":"Z. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1136\/gutjnl-2019-318843","article-title":"Albumin in decompensated cirrhosis: New concepts and perspectives","volume":"69","author":"Bernardi","year":"2020","journal-title":"Gut"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.jhep.2014.04.012","article-title":"Human serum albumin, systemic inflammation, and cirrhosis","volume":"61","author":"Arroyo","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/S0140-6736(61)92479-5","article-title":"Intravenous albumin in the treatment of diuretic-resistant ascites in portal cirrhosis","volume":"2","author":"Losowsky","year":"1961","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1053\/j.gastro.2019.03.021","article-title":"Effects of Albumin Treatment on Systemic and Portal Hemodynamics and Systemic Inflammation in Patients with Decompensated Cirrhosis","volume":"157","author":"Aguilar","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.jhep.2020.08.021","article-title":"ANSWER Study Investigators. On-treatment serum albumin level can guide long-term treatment in patients with cirrhosis and uncomplicated ascites","volume":"74","author":"Caraceni","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5444","DOI":"10.1016\/j.bbagen.2013.06.018","article-title":"Binding of transition metal ions to albumin: Sites, affinities and rates","volume":"1830","author":"Bal","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1097\/MEG.0000000000001587","article-title":"Correlation of serum zinc levels with pathological and laboratory findings in patients with nonalcoholic fatty liver disease","volume":"32","author":"Ito","year":"2020","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nutres.2019.11.009","article-title":"Zinc and protein metabolism in chronic liver diseases","volume":"74","author":"Katayama","year":"2020","journal-title":"Nutr. Res."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Nishikawa, H., Enomoto, H., Yoh, K., Iwata, Y., Sakai, Y., Kishino, K., Ikeda, N., Takashima, T., Aizawa, N., and Takata, R. (2019). Serum Zinc Concentration and Sarcopenia: A Close Linkage in Chronic Liver Diseases. J. Clin. Med., 8.","DOI":"10.3390\/jcm8030336"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1021\/ja210496n","article-title":"A molecular mechanism for modulating plasma Zn speciation by fatty acids","volume":"134","author":"Lu","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1111\/jth.12771","article-title":"Plasma free fatty acid levels influence Zn2+-dependent histidine-rich glycoprotein-heparin interactions via an allosteric switch on serum albumin","volume":"13","author":"Kassaar","year":"2015","journal-title":"J. Thromb. Haemost."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.bbalip.2018.09.007","article-title":"Crosstalk between zinc and free fatty acids in plasma","volume":"1864","author":"Coverdale","year":"2019","journal-title":"Biochim. Biophys. Acta-Mol. Cell. Biol. Lipids"},{"key":"ref_17","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_18","doi-asserted-by":"crossref","first-page":"920","DOI":"10.5604\/01.3001.0012.7192","article-title":"An Argument for Vitamin D, A, and Zinc Monitoring in Cirrhosis","volume":"17","author":"Koop","year":"2018","journal-title":"Ann. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"S49","DOI":"10.1016\/j.jhep.2021.01.002","article-title":"Pathophysiology of decompensated cirrhosis: Portal hypertension, circulatory dysfunction, inflammation, metabolism and mitochondrial dysfunction","volume":"75","author":"Engelmann","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1111\/apt.13549","article-title":"Review article: Sarcopenia in cirrhosis-aetiology, implications and potential therapeutic interventions","volume":"43","author":"Sinclair","year":"2016","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"S147","DOI":"10.1016\/j.jhep.2021.01.025","article-title":"Sarcopenia and frailty in decompensated cirrhosis","volume":"75","author":"Tandon","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.jhep.2021.01.001","article-title":"Systemic inflammation and liver cirrhosis complications: Driving or secondary event? How to square the cicle?","volume":"74","author":"Samuel","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/s41569-020-0433-5","article-title":"Interplay of cardiovascular mediators, oxidative stress and inflammation in liver disease and its complications","volume":"18","author":"Matyas","year":"2021","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.jhep.2020.10.004","article-title":"Systemic inflammation increases across distinct stages of advanced chronic liver disease and correlates with decompensation and mortality","volume":"74","author":"Costa","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1053\/j.gastro.2010.06.019","article-title":"Infections in patients with cirrhosis increase mortality four-fold and should be used in determining prognosis","volume":"139","author":"Arvaniti","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1016\/S0140-6736(14)60121-5","article-title":"Liver cirrhosis","volume":"383","author":"Tsochatzis","year":"2014","journal-title":"Lancet"},{"key":"ref_27","first-page":"1541","article-title":"Bakterien und Endotoxine bei der Leberzirrhose","volume":"36","author":"Kleine","year":"1981","journal-title":"Dt. Gesundh. Wesen."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1053\/jhep.2002.30082","article-title":"Bacterial infections in cirrhosis: Epidemiological changes with invasive procedures and norfloxacin prophylaxis","volume":"35","author":"Navasa","year":"2002","journal-title":"Hepatology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S1590-8658(01)80134-1","article-title":"Bacterial infection in patients with advanced cirrhosis: A multicentre prospective study","volume":"33","author":"Borzio","year":"2001","journal-title":"Dig. Liver Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.jhep.2013.07.044","article-title":"Pathological bacterial translocation in liver cirrhosis","volume":"60","author":"Wiest","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/liv.12021","article-title":"Pathological translocation in cirrhosis. Pathophysiology, diagnosis and clinical implications","volume":"33","author":"Bellot","year":"2013","journal-title":"Liver Int."},{"key":"ref_32","first-page":"122","article-title":"Endotoxine und RES-Funktion in der Pathogenese von Lebererkrankungen","volume":"36","author":"Liehr","year":"1976","journal-title":"Internist"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S0016-5085(76)80118-7","article-title":"The liver as an immunological organ","volume":"71","author":"Triger","year":"1976","journal-title":"Gastroenterology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1016\/S0016-5085(19)32333-9","article-title":"The role of endotoxin in liver injury","volume":"69","author":"Nolan","year":"1975","journal-title":"Gastroenterology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/clpt.2012.112","article-title":"Ammonia-lowering strategies for the treatment of hepatic encephalopathy","volume":"92","author":"Rose","year":"2012","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1002\/lt.24443","article-title":"Role of ammonia, inflammation, and cerebral oxygenation in brain dysfunction of acute-on-chronic liver failure patients","volume":"22","author":"Sawhney","year":"2016","journal-title":"Liver Transpl."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1111\/liv.12257","article-title":"Cerebral oedema is rare in acute-on-chronic liver failure patients presenting with high-grade hepatic encephalopathy","volume":"34","author":"Joshi","year":"2014","journal-title":"Liver Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1073\/pnas.74.4.1358","article-title":"Rat liver preproalbumin: In vitro synthesis and partial amino acid sequence","volume":"74","author":"Strauss","year":"1977","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","first-page":"161","article-title":"Serum albumin","volume":"37","author":"Peters","year":"1985","journal-title":"Adv. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.clnu.2015.02.010","article-title":"The effect of the systemic inflammatory response on plasma zinc and selenium adjusted for albumin","volume":"35","author":"Ghashut","year":"2016","journal-title":"Clin. Nutr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.jmb.2006.06.028","article-title":"Location of high and low affinity fatty acid binding sites on human serum albumin revealed by NMR drug-competition analysis","volume":"361","author":"Simard","year":"2006","journal-title":"J. Mol. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1002\/hep.22913","article-title":"Alterations in the functional capacity of albumin in patients with decompensated cirrhosis is associated with increased mortality","volume":"50","author":"Jalan","year":"2009","journal-title":"Hepatology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1016\/j.jhep.2018.08.006","article-title":"Midodrine and albumin for prevention of complications in patients with cirrhosis awaiting liver transplantation. A randomized placebo-controlled trial","volume":"69","author":"Castellote","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1056\/NEJMoa2022166","article-title":"A Randomized Trial of Albumin Infusions in Hospitalized Patients with Cirrhosis","volume":"384","author":"China","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1016\/S0140-6736(18)30840-7","article-title":"Long-term albumin administration in decompensated cirrhosis (ANSWER): An open-label randomised trial","volume":"391","author":"Caraceni","year":"2018","journal-title":"Lancet"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1021\/ja908878n","article-title":"Delta12-prostaglandin j2 as a product and ligand of human serum albumin: Formation of an unusual covalent adduct at His146","volume":"132","author":"Yamaguchi","year":"2010","journal-title":"J. Am. Chem. Soc."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5135","DOI":"10.1126\/scitranslmed.aax5135","article-title":"Albumin internalizes and inhibits endosomal TLR signaling in leukocytes from patients with decompensated cirrhosis","volume":"12","author":"Casulleras","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Casulleras, M., Zhang, I.W., L\u00f3pez-Vicario, C., and Cl\u00e0ria, J. (2020). Leukocytes, Systemic Inflammation and Immunopathology in Acute-on-Chronic Liver Failure. Cells, 9.","DOI":"10.3390\/cells9122632"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1021\/pr050361j","article-title":"Counting the zinc-proteins encoded in the human genome","volume":"5","author":"Andreini","year":"2006","journal-title":"J. Proteome Res."},{"key":"ref_50","unstructured":"Gr\u00fcngreiff, K. (2013). Zinc and the Liver, Dr. Falk Pharma GmbH. [1st ed.]."},{"key":"ref_51","unstructured":"Rink, L. (2011). Human Zinc Biochemistry. Zinc in Human Health, IOS Press. [1st ed.]."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.freeradbiomed.2019.01.006","article-title":"The redox biology of redox-inert ions","volume":"134","author":"Maret","year":"2019","journal-title":"Free Rad. Biol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Lin, P.H., Sermersheim, M., Li, H., Lee, P.H.U., Steinberg, S.M., and Ma, J. (2017). Zinc in Wound Healing Modulation. Nutrients, 10.","DOI":"10.3390\/nu10010016"},{"key":"ref_54","first-page":"e8197","article-title":"Role of Zinc in Mucosal Health and Disease: A Review of Physiological, Biochemical, and Molecular Processes","volume":"12","author":"Hassan","year":"2020","journal-title":"Cureus"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.ijid.2020.09.369","article-title":"Zinc deficiency induces epithelial barrier dysfunction and altered intestinal ion transport in novel murine model of Shigella flexneri diarrhea","volume":"101","author":"Sarkar","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"ref_56","unstructured":"Gr\u00fcngreiff, K., and Reinhold, D. (2007). Zink: Bedeutung in der \u00c4rtzlichen Praxis, J\u00fcrgen Hartmann Verlag. [1st ed.]."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.3389\/fimmu.2020.01712","article-title":"The Potential Impact of Zinc Supplementation on COVID-19 Pathogenesis","volume":"11","author":"Wessels","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Haase, H., and Schomburg, L. (2019). You\u2019d Better Zinc-Trace Element Homeostasis in Infection and Inflammation. Nutrients, 11.","DOI":"10.3390\/nu11092078"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Reinhold, D., Guttek, K., Reddig, A., Voss, L., Schubert, C., Kahlfuss, S., Gr\u00fcngreiff, K., Schraven, B., and Reinhold, A. (2021). Zinc Aspartate Induces IL-16 Secretion and Apoptosis in Human T Cells. Biomedicines, 9.","DOI":"10.3390\/biomedicines9030246"},{"key":"ref_60","unstructured":"Preedy, V.R., and Patel, V.B. (2018). Anti-Inflammatory and antioxidant effects and zinc deficiency. Handbook of Famine, Starvation, and Nutrient Deprevitation, Springer International Publishing AG. [1st ed.]."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1258\/ebm.2010.009258","article-title":"Free zinc ions outside a narrow concentration range are toxic to a variety of cells in vitro","volume":"235","author":"Bozym","year":"2010","journal-title":"Exp. Biol. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"176","DOI":"10.3945\/an.112.003210","article-title":"Discovery of human zinc deficiency: Its impact on human health and disease","volume":"4","author":"Prasad","year":"2013","journal-title":"Adv. Nutr."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"679S","DOI":"10.3945\/ajcn.110.005744","article-title":"Zinc: An essential but elusive nutrient","volume":"94","author":"King","year":"2011","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"S14","DOI":"10.1017\/S0007114508006818","article-title":"Indicators of zinc status at the population level: A review of the evidence","volume":"99","author":"Gibson","year":"2008","journal-title":"Br. J. Nutr."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1001S","DOI":"10.1093\/jn\/nxx036","article-title":"Biomarkers of Nutrition for Development (BOND)-Iron","volume":"148","author":"Lynch","year":"2018","journal-title":"J. Nutr."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/S0946-672X(97)80032-6","article-title":"Reference values for the trace elements copper, manganese, selenium, and zinc in the serum\/plasma of children, adolescents, and adults","volume":"11","author":"Klein","year":"1997","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1093\/jn\/nxy190","article-title":"Yet again, serum concentrations are unrelated to zinc intaks","volume":"148","author":"King","year":"2018","journal-title":"J. Nutr."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1093\/ajcn\/39.4.556","article-title":"Tissue zinc levels and zinc excretion during experimental zinc depletion in young men","volume":"39","author":"Baer","year":"1984","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1136\/jcp.37.9.1050","article-title":"Albumin bound and alpha-macroglobulin bound zinc concentrations in the sera of healthy adults","volume":"37","author":"Foote","year":"1984","journal-title":"J. Clin. Pathol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1017\/S0007114520002810","article-title":"Sensitivity and reliability of zinc transporter and metallothionein gene expression in peripheral blood mononuclear cells as indicators of zinc status: Responses to ex vivo zinc exposure and habitual zinc intake in humans","volume":"125","author":"Hennigar","year":"2021","journal-title":"Br. J. Nutr."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1093\/jn\/124.2.268","article-title":"Size of the zinc pools that exchange rapidly with plasma zinc in humans: Alternative techniques for measuring and relation to dietary zinc intake","volume":"124","author":"Miller","year":"1994","journal-title":"J. Nutr."},{"key":"ref_72","unstructured":"Rink, L. (2011). Zinc and the Liver. Zinc in Human Health, IOS Press. [1st ed.]."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Gr\u00fcngreiff, K., Gottstein, T., and Reinhold, D. (2020). Zinc deficiency-An independent risk factor in the pathogenesis of haemorrhagic stroke?. Nutrients, 12.","DOI":"10.3390\/nu12113548"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1093\/ndt\/gfaa045","article-title":"Don`t forget zinc","volume":"35","author":"Cardozo","year":"2020","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/s10522-006-9057-3","article-title":"Correlation between zinc status and immune function in the elderly","volume":"7","author":"Haase","year":"2006","journal-title":"Biogerontology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"100320","DOI":"10.1016\/j.jbc.2021.100320","article-title":"Zinc transporters and their functional integration in mammalian cells","volume":"296","author":"Kambe","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5456","DOI":"10.1016\/j.bbagen.2013.05.028","article-title":"Allosteric modulation of zinc speciation by fatty acids","volume":"1830","author":"Barnett","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.2174\/1568026616666160216155927","article-title":"Fatty Acid-Mediated Inhibition of Metal Binding to the Multi-Metal Site on Serum Albumin: Implications for Cardiovascular Disease","volume":"16","author":"Blindauer","year":"2016","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4079","DOI":"10.1039\/D0SC06605B","article-title":"Albumin-mediated alteration of plasma zinc speciation by fatty acids modulates blood clotting in type-2 diabetes","volume":"12","author":"Sobczak","year":"2021","journal-title":"Chem. Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1039\/C4MT00206G","article-title":"The biochemical effects of extracellular Zn(2+) and other metal ions are severely affected by their speciation in cell culture media","volume":"7","author":"Haase","year":"2015","journal-title":"Metallomics"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1039\/C9MT00177H","article-title":"A metalloproteomic analysis of interactions between plasma proteins and zinc: Elevated fatty acid levels affect zinc distribution","volume":"11","author":"Coverdale","year":"2019","journal-title":"Metallomics"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-1-4684-9111-1_1","article-title":"Theoretical and practical aspects of zinc uptake and absorption","volume":"249","author":"Cousins","year":"1989","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"6635","DOI":"10.1039\/C6SC02267G","article-title":"Circulatory zinc transport is controlled by distinct interdomain sites on mammalian albumins","volume":"7","author":"Handing","year":"2016","journal-title":"Chem. Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1038\/1869","article-title":"Crystal structure of human serum albumin complexed with fatty acid reveals an asymmetric distribution of binding sites","volume":"5","author":"Curry","year":"1998","journal-title":"Nat. Struct. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3701","DOI":"10.1073\/pnas.0436576100","article-title":"Interdomain zinc site on human albumin","volume":"100","author":"Stewart","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"4425","DOI":"10.1021\/jm3003137","article-title":"Allosteric inhibition of cobalt binding to albumin by fatty acids: Implications for the detection of myocardial ischemia","volume":"55","author":"Lu","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.plefa.2018.07.014","article-title":"Ischemia-modified albumin: Crosstalk between fatty acid and cobalt binding","volume":"135","author":"Coverdale","year":"2018","journal-title":"Prostaglandins Leukot. Essent. Fatty Acids"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.cca.2007.09.018","article-title":"The cobalt-albumin binding assay: Insights into its mode of action","volume":"387","author":"Rael","year":"2008","journal-title":"Clin. Chim. Acta"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1373\/clinchem.2008.123315","article-title":"Utility of serum fatty acid concentrations as a marker for acute myocardial infarction and their potential role in the formation of ischemia-modified albumin: A pilot study","volume":"55","author":"Bhagavan","year":"2009","journal-title":"Clin. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/j.jhep.2019.11.009","article-title":"Blood metabolomics uncovers inflammation-associated mitochondrial dysfunction as a potential mechanism underlying ACLF","volume":"72","author":"Moreau","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s00775-018-1554-8","article-title":"Effect of glycation on human serum albumin-zinc interaction: A biophysical study","volume":"23","author":"Iqbal","year":"2018","journal-title":"J. Biol. Inorg. Chem."},{"key":"ref_92","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_93","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1023\/A:1012942409274","article-title":"Zinc metabolism and homeostasis: The application of tracer techniques to human zinc physiology","volume":"14","author":"Krebs","year":"2001","journal-title":"Biometals"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1152\/physrev.1985.65.2.238","article-title":"Absorption, transport and hepatic metabolism of copper and zinc: Special reference to metallothionein and ceruloplasmin","volume":"65","author":"Cousins","year":"1985","journal-title":"Physiol. Rev."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"233","DOI":"10.3181\/00379727-167-41155","article-title":"Hormonal regulation of liver metallothionein zinc: Independent and synergistic action of glucagon and glucocorticoids","volume":"167","author":"Etzel","year":"1981","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s12263-009-0119-4","article-title":"Mammary gland zinc metabolism: Regulation and dysregulation","volume":"4","author":"Kelleher","year":"2009","journal-title":"Genes Nutr."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1093\/jn\/124.4.508","article-title":"Daily variation in plasma zinc concentrations in women fed meals at six-hour intervals","volume":"124","author":"King","year":"1994","journal-title":"J. Nutr."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1093\/jn\/nxx041","article-title":"The multiple faces of the metal transporter ZIP14 (SLC39A14)","volume":"148","author":"Aydemir","year":"2018","journal-title":"J. Nutr."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"4136","DOI":"10.1172\/JCI72325","article-title":"Zinc, insulin, and the liver: A m\u00e9nage \u00e0 trois","volume":"123","author":"Kebede","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"6843","DOI":"10.1073\/pnas.0502257102","article-title":"Interleukin-6 regulates the zinc transporter ZIP14 in liver and contributes to the hypozincemia of the acute-phase response","volume":"102","author":"Liuzzi","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1093\/jn\/133.4.1004","article-title":"Changes in rat hepatic gene expression in response to zinc deficiency as assessed by DNA arrays","volume":"133","author":"Dieck","year":"2003","journal-title":"J. Nutr."},{"key":"ref_102","first-page":"341","article-title":"Protective effects of zinc on oxidative stress enzymes in liver protein deficient rats","volume":"6","author":"Sidhu","year":"2004","journal-title":"Nutr. Hosp."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1093\/jn\/135.2.199","article-title":"Transcriptome and proteome analysis identifies the pathways that increase hepatic lipid accumulation in zinc-deficient rats","volume":"135","author":"Dieck","year":"2005","journal-title":"J. Nutr."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1111\/j.1365-2362.1977.tb01573.x","article-title":"Reduced binding of added zinc in serum of patients with decompensated hepatic cirrhosis","volume":"7","author":"Giroux","year":"1977","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_105","first-page":"926","article-title":"Metabolism after injury. I. Effects of severity, nutrition, and environmental temperature on protein potassium, zinc, and creatine","volume":"59","author":"Cuthbertson","year":"1972","journal-title":"Br. J. Surg."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1042\/cs0780547","article-title":"Tissue zinc status and drug elimination in patients with chronic liver disease","volume":"78","author":"Barry","year":"1990","journal-title":"Clin. Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.aohep.2019.08.011","article-title":"Role of zinc supplementation in the management of chronic liver diseases: A systematic review and meta-analysis","volume":"19","author":"Diglio","year":"2020","journal-title":"Ann. Hepatol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"389","DOI":"10.4254\/wjh.v12.i7.389","article-title":"Effect of zinc treatment on clinical outcomes in patients with liver cirrhosis: A systematic review and meta-analysis","volume":"12","author":"Tan","year":"2020","journal-title":"World J. Hepatol."},{"key":"ref_109","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_110","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1002\/ncp.10451","article-title":"Micronutrients in Liver Disease: Roles, Risk Factors for Deficiency, and Recommendations for Supplementation","volume":"35","author":"Kozeniecki","year":"2020","journal-title":"Nutr. Clin. Pract."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1002\/(SICI)1520-670X(2000)13:1<21::AID-JTRA4>3.0.CO;2-S","article-title":"Zinc deficiency and hepatic encephalopathy: Results of a long-term follow-up on zinc supplementation","volume":"13","author":"Reinhold","year":"2000","journal-title":"J. Trace Elem. Exp. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"126635","DOI":"10.1016\/j.jtemb.2020.126635","article-title":"The effects of zinc supplementation on metabolic profile and oxidative stress in overweight\/obese patients with non-alcoholic fatty liver disease: A randomized, double-blind, placebo-controlled trial","volume":"62","author":"Fathi","year":"2020","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"e000140","DOI":"10.1136\/bmjopen-2011-000140","article-title":"Viusid, a nutritional supplement, increases survival and reduces disease progression in HCV-related decompensated cirrhosis: A randomised and controlled trial","volume":"1","year":"2011","journal-title":"BMJ Open"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1111\/j.1365-2036.2010.04448.x","article-title":"Clinical trial: Oral zinc in hepatic encephalopathy","volume":"32","author":"Takuma","year":"2010","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/S0140-6736(84)92567-4","article-title":"Oral zinc supplementation improves hepatic encephalopathy. Results of a randomised controlled trial","volume":"2","author":"Reding","year":"1984","journal-title":"Lancet"},{"key":"ref_116","unstructured":"Boyer, J.L., and Bianchi, L. (1987). Zinc and vitamin A in liver cirrhosis. Liver Cirrhosis, MTP Press Limited. [1st ed.]."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1016\/0016-5085(91)90290-2","article-title":"Overt hepatic encephalopathy precipitated by zinc deficiency","volume":"100","author":"Schalm","year":"1991","journal-title":"Gastroenterology"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Horiguchi, S., Naganuma, A., Tateyama, Y., Suzuki, Y., Hoshino, T., Saito, N., Hatanaka, T., Takakusagi, S., Kosone, T., and Takagi, H. (2021). Efficacy of Zinc Acetate Treatment for Patients with Decompensated Liver Cirrhosis Complicated by Hypozincemia. Biol. Trace. Elem. Res., 1\u20138.","DOI":"10.1007\/s12011-021-02675-5"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1111\/hepr.13601","article-title":"Zinc deficiency predicts overt hepatic encephalopathy and mortality in liver cirrhosis patients with minimal hepatic encephalopathy","volume":"51","author":"Miwa","year":"2021","journal-title":"Hepatol. Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1007\/BF01307509","article-title":"Short-term oral zinc supplementation does not improve chronic hepatic encephalopathy. Results of a double-blind crossover trial","volume":"36","author":"Riggio","year":"1991","journal-title":"Dig. Dis. Sci."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"54","DOI":"10.4292\/wjgpt.v1.i2.54","article-title":"Hepatic encephalopathy therapy: An overview","volume":"1","author":"Riggio","year":"2010","journal-title":"World J. Gastrointest. Pharmacol. Ther."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s11011-008-9125-2","article-title":"RNA oxidation and zinc in hepatic encephalopathy and hyperammonemia","volume":"24","author":"Schliess","year":"2009","journal-title":"Metab. Brain Dis."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1002\/hep.23367","article-title":"Ammonia and the neutrophil in the pathogenesis of hepatic encephalopathy in cirrhosis","volume":"51","author":"Shawcross","year":"2010","journal-title":"Hepatology"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"483","DOI":"10.7326\/0003-4819-89-4-483","article-title":"Experimental zinc deficiency in humans","volume":"89","author":"Prasad","year":"1978","journal-title":"Ann. Intern. Med."},{"key":"ref_125","first-page":"E203","article-title":"Plasma ammonia and liver ornithine transcarbamoylase activity in zinc-deficient rats","volume":"235","author":"Rabbani","year":"1978","journal-title":"Am. J. Physiol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1002\/hep.510230523","article-title":"Zinc supplementation and amino acid-nitrogen metabolism in patients with advanced cirrhosis","volume":"23","author":"Marchesini","year":"1996","journal-title":"Hepatology"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1080\/07315724.1990.10720372","article-title":"Effects of one year of supplementation with zinc and other micronutrients on cellular immunity in the elderly","volume":"9","author":"Bogden","year":"1990","journal-title":"J. Am. Coll. Nutr."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1001\/jama.1984.03350110043027","article-title":"Excessive intake of zinc impairs immune responses","volume":"252","author":"Chandra","year":"1984","journal-title":"JAMA"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1002\/(SICI)1520-670X(1997)10:1<19::AID-JTRA3>3.0.CO;2-#","article-title":"Zinc regulates DNA synthesis and IL-2, IL-6 and IL-10 production of PWM-stimulated PBMC and normalises the periphere cytokine concentration in chronic liver disease","volume":"10","author":"Reinhold","year":"1997","journal-title":"J. Trace Elem. Exp. Med."},{"key":"ref_130","first-page":"134","article-title":"Essentiality and toxicity of zinc","volume":"19","author":"Prasad","year":"1993","journal-title":"Scand. J. Work Environ. Health"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.5005\/jp-journals-10071-23938","article-title":"Mucormycosis in COVID-19: Is Zinc a Silent Killer in India?","volume":"25","author":"Nath","year":"2021","journal-title":"Indian J. Crit. Care Med."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1039\/C4MT00331D","article-title":"An evolutionary perspective on zinc uptake by human fungal pathogens","volume":"7","author":"Wilson","year":"2015","journal-title":"Metallomics"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"65","DOI":"10.3389\/fcimb.2013.00065","article-title":"Fungal zinc metabolism and its connections to virulence","volume":"3","author":"Staats","year":"2013","journal-title":"Front. Cell Infect. Microbiol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/11\/4011\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:28:07Z","timestamp":1760167687000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/11\/4011"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,10]]},"references-count":133,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["nu13114011"],"URL":"https:\/\/doi.org\/10.3390\/nu13114011","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,10]]}}}