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Removal of Metabolites, Cytokines and Hepatic Growth Factors by Extracorporeal Liver Support in Children

Auth, Marcus KH.*; Kim, Hyun Soo*; Beste, Mechthild†; Bonzel, Klaus E.‡; Baumann, Ulrich; Ballauff, Antje*; Wallot, Michael*; Borchers, Tanja*; Vester, Udo‡; Grasemann, Corinna*; Hauffa, Berthold§; Hoyer, Peter F.‡; Gerken, Guido†; Voit, Thomas*

Journal of Pediatric Gastroenterology & Nutrition:
Original Articles: Hepatology and Nutrition
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-α (TNF-α), interleukin-6 (IL-6), methionine, cystine and hyaluronic acid] and hepatic growth factors [hepatocyte growth factor (HGF), epidermal growth factor (EGF), transforming growth factor-β1 (TGF-β1), cortisol, corticosteroid-binding globulin (CBG), insulin-like growth factor-1 (IGF-1), angiogenin, vascular endothelial growth factor (VEGF), IL-6 and TNF-α] 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.

Author Information

Department of Paediatrics, Division of *General Paediatrics; †Department of Internal Medicine, Division of Gastroenterology; Department of Paediatrics, Divisions of ‡Paediatric Nephrology and §Paediatric Haematology, Oncology and Endocrinology, University Hospital of Essen, Hufelandstr, Essen, Germany

Received February 10, 2004; accepted August 16, 2004.

Supported by DFG-grant AU 117/4-1 and 4-2.

Address correspondence and reprint requests to Dr. Marcus K.H. Auth, Universitäts-Kinderklinik, Abteilung für Allgemeine Pädiatrie, Hufelandstr. 55, D-45122 Essen, Germany (e-mail: marcus.auth@uni-essen.de).

© 2005 Lippincott Williams & Wilkins, Inc.