title: Alcoholic Hepatitis Markedly Decreases the Capacity for Urea Synthesis.
abstract: OBJECTIVE
  Data on quantitative metabolic liver functions in the life-threatening disease alcoholic hepatitis are scarce. Urea synthesis is an essential metabolic liver function that plays a key regulatory role in nitrogen homeostasis. The urea synthesis capacity decreases in patients with compromised liver function, whereas it increases in patients with inflammation. Alcoholic hepatitis involves both mechanisms, but how these opposite effects are balanced remains unclear. Our aim was to investigate how alcoholic hepatitis affects the capacity for urea synthesis. We related these findings to another measure of metabolic liver function, the galactose elimination capacity (GEC), as well as to clinical disease severity.
  
  
  METHODS
  We included 20 patients with alcoholic hepatitis and 7 healthy controls. The urea synthesis capacity was quantified by the functional hepatic nitrogen clearance (FHNC), i.e., the slope of the linear relationship between the blood α-amino nitrogen concentration and urea nitrogen synthesis rate during alanine infusion. The GEC was determined using blood concentration decay curves after intravenous bolus injection of galactose. Clinical disease severity was assessed by the Glasgow Alcoholic Hepatitis Score and Model for End-Stage Liver Disease (MELD) score.
  
  
  RESULTS
  The FHNC was markedly decreased in the alcoholic hepatitis patients compared with the healthy controls (7.2±4.9 L/h vs. 37.4±6.8 L/h, P<0.01), and the largest decrease was observed in those with severe alcoholic hepatitis (4.9±3.6 L/h vs. 9.9±4.9 L/h, P<0.05). The GEC was less markedly reduced than the FHNC. A negative correlation was detected between the FHNC and MELD score (rho = -0.49, P<0.05).
  
  
  CONCLUSIONS
  Alcoholic hepatitis markedly decreases the urea synthesis capacity. This decrease is associated with an increase in clinical disease severity. Thus, the metabolic failure in alcoholic hepatitis prevails such that the liver cannot adequately perform the metabolic up-regulation observed in other stressful states, including extrahepatic inflammation, which may contribute to the patients' poor prognosis.
authors.affiliation: Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Emilie
authors.initials: E
authors.lastname: Glavind
authors.affiliation: Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Niels Kristian
authors.initials: NK
authors.lastname: Aagaard
authors.affiliation: Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Henning
authors.initials: H
authors.lastname: Grønbæk
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Holger Jon
authors.initials: HJ
authors.lastname: Møller
authors.affiliation: Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Nikolaj Worm
authors.initials: NW
authors.lastname: Orntoft
authors.affiliation: Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Vilstrup
authors.affiliation: Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Karen Louise
authors.initials: KL
authors.lastname: Thomsen
mesh_terms: D000328:Adult; D000409:Alanine / Q000008:administration & dosage / Q000378:metabolism; D015703:Antigens, CD / Q000097:blood; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D005167:Factor VII / Q000378:metabolism; D005170:Factor X / Q000378:metabolism; D005260:Female; D005690:Galactose / Q000008:administration & dosage / Q000378:metabolism; D005934:Glucagon / Q000097:blood; D006519:Hepatitis, Alcoholic / Q000097:blood / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016014:Linear Models; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009584:Nitrogen / Q000378:metabolism*; D011379:Prognosis; D011516:Prothrombin / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000097:blood; D014508:Urea / Q000378:metabolism*; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001786:Blood Glucose; D000098902:CD163 Antigen; D007328:Insulin; D015850:Interleukin-6; D011956:Receptors, Cell Surface; D014508:Urea; D005167:Factor VII; D011516:Prothrombin; D005170:Factor X; D002097:C-Reactive Protein; D005934:Glucagon; D009584:Nitrogen; D000409:Alanine; D005690:Galactose