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Role of predisposition, injury, response and organ failure in the prognosis of patients with acute-on-chronic liver failure: a prospective cohort study

Rajiv Jalan1*, Vanessa Stadlbauer12, Sambit Sen1, Lisa Cheshire1, Yu-Mei Chang3 and Rajeshwar P Mookerjee1

Author Affiliations

1 The Liver Failure Group, Institute of Liver and Digestive Health, UCL Medical School, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, UK

2 Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria

3 Research Support Office, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK

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Critical Care 2012, 16:R227  doi:10.1186/cc11882

Published: 27 November 2012



Acute deterioration of cirrhosis is associated with high mortality rates particularly in the patients who develop organ failure (OF), a condition that is referred to as acute-on-chronic liver failure (ACLF), which is currently not completely defined. This study aimed to determine the role of predisposing factors, the nature of the precipitating illness and inflammatory response in the progression to OF according to the PIRO (predisposition, injury, response, organ failure) concept to define the risk of in-hospital mortality.


A total of 477 patients admitted with acute deterioration of cirrhosis following a defined precipitant over a 5.5-year period were prospectively studied. Baseline clinical, demographic and biochemical data were recorded for all patients and extended serial data from the group that progressed to OF were analysed to define the role of PIRO in determining in-hospital mortality.


One hundred and fifty-nine (33%) patients developed OF, of whom 93 patients died (58%) compared with 25/318 (8%) deaths in the non-OF group (P < 0.0001). Progression to OF was associated with more severe underlying liver disease and inflammation. In the OF group, previous hospitalisation (P of PIRO); severity of inflammation and lack of its resolution (R of PIRO); and severity of organ failure (O of PIRO) were associated with significantly greater risk of death. In the patients who recovered from OF, mortality at three years was almost universal.


The results of this prospective study shows that the occurrence of OF alters the natural history of cirrhosis. A classification based on the PIRO concept may allow categorization of patients into distinct pathophysiologic and prognostic groups and allow a multidimensional definition of ACLF.