title: Infection and systemic inflammation, not ammonia, are associated with Grade 3/4 hepatic encephalopathy, but not mortality in cirrhosis.
abstract: OBJECTIVE
  Patients with cirrhosis are prone to infection which is a frequent precipitant of hepatic encephalopathy (HE). Clinical studies have examined the importance of inflammation and infection in modulating the manifestation of symptoms of HE in acute liver failure and patients with cirrhosis and minimal/low grade HE. It would be logical to presume that this relationship persists in patients who develop severe HE in cirrhosis although this has not been examined to date.
  
  
  METHODS
  We report the findings of a prospective audit of 100 consecutive patients with cirrhosis admitted between Jan 2000 and March 2008 to a liver Intensive Care Unit (ICU) where HE was the primary indication for admission (59% Grade 3; 41% Grade 4). Haematological and microbiological data were collected at ICU admission, and organ scores and outcomes were recorded.
  
  
  RESULTS
  46% of patients had positive cultures taken within ± 48h from admission to ICU [25% blood] and a further 22% were culture negative but had evidence of systemic inflammation (SIRS). SIRS score (p=0.03) and SOFA score (p=0.006) were significantly higher in those patients with Grade 4 HE, who were also less likely to survive (p<0.001). HE grade/coma score did not correlate with ammonia, biochemistry or MELD score. Fifty-two percent of patients survived their ICU stay while the remainder developed progressive multiorgan failure and died; 38% survived to discharge, and 16% were transplanted.
  
  
  CONCLUSIONS
  These data support an association between infection/SIRS and not ammonia, in patients with cirrhosis that develop severe HE. The presence or absence of infection/SIRS did not determine survival.
authors.affiliation: Institute of Liver Studies, King's College London School of Medicine, London, UK. debbie.shawcross@kcl.ac.uk
authors.forename: D L
authors.initials: DL
authors.lastname: Shawcross
authors.forename: Y
authors.initials: Y
authors.lastname: Sharifi
authors.forename: J B
authors.initials: JB
authors.lastname: Canavan
authors.forename: A D
authors.initials: AD
authors.lastname: Yeoman
authors.forename: R D
authors.initials: RD
authors.lastname: Abeles
authors.forename: N J
authors.initials: NJ
authors.lastname: Taylor
authors.forename: G
authors.initials: G
authors.lastname: Auzinger
authors.forename: W
authors.initials: W
authors.lastname: Bernal
authors.forename: J A
authors.initials: JA
authors.lastname: Wendon
mesh_terms: D000328:Adult; D000641:Ammonia / Q000097:blood; D003422:Critical Care; D005260:Female; D006501:Hepatic Encephalopathy / Q000097:blood / Q000209:etiology* / Q000401:mortality; D006506:Hepatitis A / Q000150:complications / Q000382:microbiology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008103:Liver Cirrhosis / Q000097:blood / Q000150:complications* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018746:Systemic Inflammatory Response Syndrome / Q000150:complications
chemical_list: D000641:Ammonia