Abstract
Decompensated liver cirrhosis has a dismal prognosis, with patients surviving on average for 2–4 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.
Highlights
Human serum albumin is the most abundant protein in blood plasma, reaching concentrations of around 35–50 g L−1 in healthy conditions
This review focuses on Zn2+ because there is a clear correlation between zinc and albumin status in a range of conditions [11,12,13], and a well-founded understanding of structure, affinity, and allosteric effects on the major zinc-binding site of albumin [14,15,16]
In Samuel’s view, there is a need for further immunological insights regarding cellular immunity, and he asks whether systemic inflammation is a primary or secondary event in liver disease [22]
Summary
Human serum albumin is the most abundant protein in blood plasma, reaching concentrations of around 35–50 g L−1 in healthy conditions. Despite the recognized benefits of short-term albumin infusions to treat ascites, intravenous long-term treatments with albumin have gained significant importance only in the past decade, after the recognition of a range of non-oncotic effects of albumin. These effects include albumin’s scavenger function, its role in the maintenance of endothelial function, and more generally anti-inflammatory, antioxidant, and immunomodulatory effects [5,8]. Whilst “albumin binding function” has been proposed as one measure to assess the levels of effective albumin [5], at least one important physiological function of albumin often gets overlooked, namely its role as important physiological transporter of metal ions in the bloodstream. S[u6b]s. eqSuuebnset qmueetn‐ t maebtoalbicoclihcacnhgaensgleeasdletaodhetomhoedmynoadmyincaamltiecraatlitoenrsa,ticoanrds,iocvaardsciuolvaarsdcuyslafurndcytisofnu,ntcistisoune,dtaismsu‐ e daagmeaagnedaenxdtreaxhterpaahteicpaotrigcaonrgfaainlufraeil(ukriden(ekyid, nheeya,rth, eluarntg, slu, anngds,barnadinb),raanind),saenvedreseivmepreaiirm‐ pmaiermnteonft tohfethime mimumneunsyessteymst.emTh.iTs himispimairpmaiernmt einnctrienacsreesassuesscseupstciebpiltitibyiltiotyantodasnedvesreitvyeroifty obf abcatcetreiarilailnifnefcetciotinosn, sw, whihchicharaerealaslosoprpormomotoetdedbybyinicnrceraesaesdedgugtutpperemrmeaebaibliitlyit,yw, whihcihchcacnan lelaeaddtototrtraannssloloccaattioionnooffbbaacctteerriiaa oorr tthheeiirr ccoommppoonneennttssaannddeennddoottooxxeemmiaia..BBaactceterirailalpprordoduuctcsts araeresosmometeitmimesesrerfeefrerrerdedtotaosapsapthaothgoegne-ans‐saoscsoiactieadtemd omleoclueclaurlapratptaetrtnesrn(PsA(PMAPMs)Pasn)danindcliund‐ e licploupdoelylispaocpcholayrsidacecsh, apreipdteisd,opgelypctiadnosg, lflyacgaenlsl,infl,aagnedllinnu, calneidc ancuicdlseifcroamcidpsatfhroomgenpsa.thTooggeenths.er wTiothgedthamerawgeit-hassdoacmiaatgeed‐amssoolceicauteldar mpaotletecrunlasr(DpaAttMerPnss, (wDhAicMhPasr, iswehfircohmarcieslel dfreoamthcaenlld tidsseuatehdaanmd atigsesu, einditaimalalygeo,finthiteiallilvyeorf),ththeelisvee“r)d, athnegseer“mdaonlegceurlmeso”leacrueleasm” oarnegasmt tohnegfsatctthoers pfraocmtoortsinpgrotmheotdinevgetlhoepdmeevnetloopfmboentht olofcbaolitzheldocaanlidzesdysatnemd sicysinteflmamic minafltaiomnm[1a9ti]o. n [19]
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