Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis

Moreau, Richard; Jalan, Rajiv; Gines, Pere; Pavesi, Marco; Angeli, Paolo; Cordoba, Juan; Durand, Francois; Gustot, Thierry; Saliba, Faouzi; Domenicali, Marco; Gerbes, Alexander; Wendon, Julia; Alessandria, Carlo; Laleman, Wim; Zeuzem, Stefan; Trebicka, Jonel; Bernardi, Mauro; Arroyo, Vicente; De Gottardi, Andrea and CANONIC Study Investigators of the EASL, CLIF Consortium (2013). Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology, 144(7), pp. 1426-1437. Elsevier 10.1053/j.gastro.2013.02.042

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BACKGROUND & AIMS

Patients with cirrhosis hospitalized for an acute decompensation (AD) and organ failure are at risk for imminent death and considered to have acute-on-chronic liver failure (ACLF). However, there are no established diagnostic criteria for ACLF, so little is known about its development and progression. We aimed to identify diagnostic criteria of ACLF and describe the development of this syndrome in European patients with AD.

METHODS

We collected data from 1343 hospitalized patients with cirrhosis and AD from February to September 2011 at 29 liver units in 8 European countries. We used the organ failure and mortality data to define ACLF grades, assess mortality, and identify differences between ACLF and AD. We established diagnostic criteria for ACLF based on analyses of patients with organ failure (defined by the chronic liver failure-sequential organ failure assessment [CLIF-SOFA] score) and high 28-day mortality rate (>15%).

RESULTS

Of the patients assessed, 303 had ACLF when the study began, 112 developed ACLF, and 928 did not have ACLF. The 28-day mortality rate among patients who had ACLF when the study began was 33.9%, among those who developed ACLF was 29.7%, and among those who did not have ACLF was 1.9%. Patients with ACLF were younger and more frequently alcoholic, had more associated bacterial infections, and had higher numbers of leukocytes and higher plasma levels of C-reactive protein than patients without ACLF (P < .001). Higher CLIF-SOFA scores and leukocyte counts were independent predictors of mortality in patients with ACLF. In patients without a prior history of AD, ACLF was unexpectedly characterized by higher numbers of organ failures, leukocyte count, and mortality compared with ACLF in patients with a prior history of AD.

CONCLUSIONS

We analyzed data from patients with cirrhosis and AD to establish diagnostic criteria for ACLF and showed that it is distinct from AD, based not only on the presence of organ failure(s) and high mortality rate but also on age, precipitating events, and systemic inflammation. ACLF mortality is associated with loss of organ function and high leukocyte counts. ACLF is especially severe in patients with no prior history of AD.

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