From the AGA Journals

High mortality seen in acute-on-chronic liver failure

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ACLF is a problem that needs a definition

The study by Moreau and colleagues represents a culmination of efforts to bring together a continent’s worth of experience in research and patient care into defining an important issue that has been struggling to find a definition: acute-on-chronic liver failure or ACLF. This important study crucially separates ACLF as an entity distinct

from mere decompensation of cirrhosis, something that has long confused the

picture among clinicians. The definition of organ failure, the basis for ACLF,

was determined a priori by expert opinion. The team found a significantly poorer

prognosis in patients with more than two organ failures, especially renal

failure. An intriguing finding was the better prognosis of previously

decompensated cirrhotic patients compared with those without prior

decompensation, which should form the basis for future investigation into the

relationship of ACLF with potential immune tolerance. Other interesting points

raised, such as the absence of precipitating factors in almost half of the ACLF

cases, and correlation of outcomes with leukocyte count and C-reaction protein,

need further corroboration since a large proportion of patients had an

alcoholic etiology. In a large study, it is not always possible to have uniform

precipitating factor investigations. Importantly, these results have also been

corroborated by the initial reports on ACLF using simpler criteria for organ

failure in the North American Consortium for End-Stage Liver Disease (NACSELD).

As the cirrhotic population in Western countries ages along with a scarcity of

donor organs and the emergence of resistant pathogens, the knowledge of ACLF is

going to be increasingly relevant and further large, collaborative studies are

needed along the lines of this paper to tackle this growing issue.

Dr. Jasmohan Bajaj is in the division of gastroenterology, hepatology,

and nutrition at Virginia Commonwealth University and at McGuire VA Medical

Center, Richmond.

His institution has received grants from, and he has been a consultant to,

Grifols, Salix, and Otsuka. He has received an honorarium from Merz.



An attempt to define and classify acute-on-chronic liver failure showed that the syndrome carries a 28-day mortality rate that is 15 times greater than in cirrhosis patients who do not have the syndrome.

Moreover, the syndrome is extremely common, and may be found in nearly one-third of acutely decompensated cirrhosis patients, wrote Dr. Richard Moreau and colleagues. The study was published in the June issue of Gastroenterology.

Source: American Gastroenterological Association

"A universally accepted and used definition of acute-on-chronic liver failure (ACLF) is still lacking," said Dr. Moreau of Université Paris Diderot, Paris.

"Defining ACLF is not only a matter of nosology, but also is of great importance because it would allow early identification of patients at high risk for end-organ failure–related death, requiring specific treatments and/or intensive management," he added.

To that end, Dr. Moreau looked at 1,343 adult patients hospitalized for at least 1 day who had an acute decompensation of cirrhosis as defined by the acute development of large ascites, hepatic encephalopathy, gastrointestinal hemorrhage, bacterial infection, or any combination of the above.

Patients who were admitted for a scheduled procedure or treatment were excluded from the analysis, as were patients with severe chronic extrahepatic disease and patients with HIV infection.

The study subjects were then divided into four groups. The first group, which was judged not to have ACLF, had no organ failure, a serum creatinine less than 1.5 mg/dL, and no hepatic encephalopathy. This group made up 1,040 of the 1,343 enrolled patients (77.4%), and had 28-day and 90-day mortality rates of 4.7% and 14%, respectively.

The next cohort, called ACLF grade 1, comprised patients with a single coagulation, circulatory or respiratory failure; a serum creatinine between 1.5 and 1.9 mg/dL; and/or mild to moderate hepatic encephalopathy. The 148 patients in this class (11.0%) had 28- and 90-day mortality rates of 22.1% and 40.7%, respectively.

ACLF grade 2 was more severe, with two organ failures; 108 patients (8%) had this at enrollment, and exhibited 28- and 90-day mortality rates of 32.0% and 40.7%, respectively.

The most severely ill patients were classed as having ACLF grade 3, with three organ failures or more. A total of 47 patients (3.5%) fell into this category, and they had 28- and 90-day mortality rates of 76.7% and 79.1%, respectively.

Overall, according to the investigators, patients with ACLF were younger (mean age 56 years versus 58 years in patients without ACLF; P = .02), had a lower mean arterial blood pressure on admittance to the hospital (79 mm Hg versus 85 mm Hg in non-ACLF patients; P less than .001) and more frequently were actively alcoholic.

They also found that patients with ACLF had a significantly higher white cell count (9.7 x 109 compared with 6.6 x 109/L; P less than .001) and plasma C-reactive protein level (40.3 versus 24.9 mg/L; P less than .001) than the group without ACLF.

And finally, in what they called an "outstanding observation," the authors determined that up to 43.6% of patients with ACLF had no precipitating event leading to their acute decompensation, including gastrointestinal hemorrhage, bacterial infection, or active alcoholism.

The authors concluded that their novel diagnostic criteria show that ACLF is "distinct from ‘mere’ AD."

They conceded that their study was not designed to assess ideal management for these patients. "Whether patients with ACLF should be admitted or not to the intensive care unit is controversial," they wrote. "Nevertheless, our results can serve as a resource for designing studies aimed to investigate the appropriate site of hospitalization for patients with ACLF."

The authors disclosed that pharmaceutical companies provided funding for a chronic liver failure consortium, which provided the initiative for this study; several other investigators also disclosed ties with pharmaceutical companies.

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