title: Infection and the progression of hepatic encephalopathy in acute liver failure.
abstract: OBJECTIVE
  Progression of hepatic encephalopathy (HE) is a major determinant of outcome in acute liver failure (ALF). Our aim was to identify predictive factors of worsening HE, including the relation of encephalopathy with the systemic inflammatory response (SIRS) and infection.
  
  
  METHODS
  We included 227 consecutive patients with stage I-II HE prospectively enrolled in the U.S. Acute Liver Failure Study. Univariate and multivariate analysis of 27 variables at admission were performed separately for acetaminophen (n = 96) and nonacetaminophen (n = 131) etiologies.
  
  
  RESULTS
  On multivariate analysis, acquisition of infection during stage I-II HE (P < 0.01), increased leukocyte levels at admission (P < 0.01), and decreased platelet count (P < 0.05) were predictive factors of worsening HE in the acetaminophen group. By contrast, only increased pulse rate (P < 0.05) and AST levels (P < 0.05) at admission were predictors in nonacetaminophen patients. In patients who progressed to deep HE, the first confirmed infection preceded progression in 15 of 19 acetaminophen patients compared with 12 of 23 nonacetaminophen patients. In patients who did not demonstrate positive microbiologic cultures, a higher number of components of SIRS at admission was associated with more frequent worsening of HE (25% vs. 35% vs. 50% for 0, 1, and >or=2 components of SIRS, P < 0.05). CONCLUSIONA: This prospective evaluation points to infection and/or the resulting systemic inflammatory response as important factors contributing to worsening HE in ALF, mainly in patients with acetaminophen- induced ALF. The use of prophylactic antibiotics in these patients and the mechanisms by which infection triggers hepatic encephalopathy require further investigation.
authors.affiliation: Department of Medicine, Freidburg Medical Schoolm Northwestern University, Chicago, Illinois, USA.
authors.forename: Javier
authors.initials: J
authors.lastname: Vaquero
authors.forename: Julie
authors.initials: J
authors.lastname: Polson
authors.forename: Chuhan
authors.initials: C
authors.lastname: Chung
authors.forename: Irene
authors.initials: I
authors.lastname: Helenowski
authors.forename: Frank V
authors.initials: FV
authors.lastname: Schiodt
authors.forename: Joan
authors.initials: J
authors.lastname: Reisch
authors.forename: William M
authors.initials: WM
authors.lastname: Lee
authors.forename: Andres T
authors.initials: AT
authors.lastname: Blei
mesh_terms: D000082:Acetaminophen / Q000633:toxicity; D000328:Adult; D018450:Disease Progression; D005260:Female; D006501:Hepatic Encephalopathy / Q000209:etiology*; D006801:Humans; D007239:Infections / Q000209:etiology*; D017114:Liver Failure, Acute / Q000150:complications*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology
chemical_list: D000082:Acetaminophen