Infection and systemic inflammation, not ammonia, are associated with Grade III/IV hepatic encephalopathy, but not mortality in cirrhosis

Articles in Press

D.L. Shawcross 1‡, Y. Sharifi 1‡, J.B. Canavan 3, A.D. Yeoman 12, R.D. Abeles 12, N.J. Taylor 1, G. Auzinger 2, W. Bernal 12, J.A. Wendon 12

Received 19 April 2010; received in revised form 23 June 2010; accepted 14 July 2010. published online 01 December 2010.
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Background & Aims
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 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.

Keywords: Hepatic encephalopathy, Cirrhosis, Inflammation, Infection, Outcomes

Abbreviations: APACHE, Acute Physiology and Chronic Health Evaluation, CRP, C-reactive protein, GCS, Glasgow Coma Score, HE, hepatic encephalopathy, HDU, High Dependency Unit, ICU, Intensive Care Unit, MELD, Model for End-stage Liver Disease, SIRS, Systemic Inflammatory Response Syndrome, SOFA, Sequential Organ Failure Assessment

1 Institute of Liver Studies, King’s College London School of Medicine at King’s College Hospital, Denmark Hill, London, UK
2 Liver Intensive Therapy Unit, King’s College Hospital, Denmark Hill, London, UK
3 NIHR Comprehensive Biomedical Research Centre at Guy’s & St. Thomas’s NHS Foundation Trust and King’s College London, UK

Corresponding author. Address: Institute of Liver Studies, King’s College Hospital, Denmark Hill, London SE5 9RS, UK. Tel.: +44 20 3299 2316; fax: +44 20 3299 3167.

‡ These authors contributed equally to this paper.

PII: S0168-8278(10)00838-X
doi:10.1016/j.jhep.2010.07.045
© 2010 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.

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