title: Removal of metabolites, cytokines and hepatic growth factors by extracorporeal liver support in children.
abstract: BACKGROUND
  Molecular Adsorbents Recirculating System (MARS)-mini has recently been approved and applied in children with hepatic failure. However, its indication, efficacy and capability to induce liver regeneration remain unclear. The aim of our pilot study in children was to analyse the impact of MARS on markers of detoxification and regeneration.
  
  
  METHODS
  In children with fulminant Wilson's disease and bridged with MARSmini for liver transplantation, we analyzed toxic metabolites (bile acids, bilirubin, lactate, ammonia, tryptophan and copper), regulators of the inflammatory cascade [nitrate, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), methionine, cystine and hyaluronic acid] and hepatic growth factors [hepatocyte growth factor (HGF), epidermal growth factor (EGF), transforming growth factor-beta1 (TGF-beta1), cortisol, corticosteroid-binding globulin (CBG), insulin-like growth factor-1 (IGF-1), angiogenin, vascular endothelial growth factor (VEGF), IL-6 and TNF-alpha] from blood, albumin circuit and haemodialysate from four applications.
  
  
  RESULTS
  In all four applications, transfer of toxic metabolites (6/6) and inflammatory mediators (6/6), but also of hepatic growth factors (9/10), into the albumin circuit of MARS was consistently detected. Corresponding blood levels were decreased for 3/6 metabolites, 3/6 inflammatory mediators and 1/10 growth factors and increased for 1/10 growth factors. Bridging for liver transplantation was successful with MARS.
  
  
  CONCLUSIONS
  In our prospective study, substantial extraction of albumin-bound and water-soluble candidate substances was detected with variable effect on respective blood levels. Notably, essential factors inducing liver regeneration were simultaneously removed. These data provide a basis for evaluation of liver restoration and efficacy of liver support in children with liver failure to devise a collaborative, multicentre trial.
authors.affiliation: Department of Paediatrics, Division of General Paediatrics, University Hospital of Essen, Hufelandstr, Essen, Germany. marcus.auth@uni-essen.de
authors.forename: Marcus K H
authors.initials: MK
authors.lastname: Auth
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Mechthild
authors.initials: M
authors.lastname: Beste
authors.forename: Klaus E
authors.initials: KE
authors.lastname: Bonzel
authors.forename: Ulrich
authors.initials: U
authors.lastname: Baumann
authors.forename: Antje
authors.initials: A
authors.lastname: Ballauff
authors.forename: Michael
authors.initials: M
authors.lastname: Wallot
authors.forename: Tanja
authors.initials: T
authors.lastname: Borchers
authors.forename: Udo
authors.initials: U
authors.lastname: Vester
authors.forename: Corinna
authors.initials: C
authors.lastname: Grasemann
authors.forename: Berthold
authors.initials: B
authors.lastname: Hauffa
authors.forename: Peter F
authors.initials: PF
authors.lastname: Hoyer
authors.forename: Guido
authors.initials: G
authors.lastname: Gerken
authors.forename: Thomas
authors.initials: T
authors.lastname: Voit
mesh_terms: D000293:Adolescent; D002648:Child; D016207:Cytokines / Q000097:blood*; D005112:Extracorporeal Circulation / Q000379:methods*; D005260:Female; D006527:Hepatolenticular Degeneration / Q000150:complications*; D006801:Humans; D008099:Liver / Q000254:growth & development*; D017093:Liver Failure / Q000097:blood / Q000209:etiology / Q000628:therapy*; D016031:Liver Transplantation; D011446:Prospective Studies; D006435:Renal Dialysis; D016060:Sorption Detoxification; D014118:Toxins, Biological / Q000097:blood*; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D014118:Toxins, Biological