Acute-on-chronic liver failure defined as distinct syndrome

BOSTON — The results of the CANONIC study, presented at The Liver Meeting, suggest that acute-on-chronic liver failure is a clinically distinct condition, with a high mortality rate, and common among cirrhotic patients.

During an 8-month period, researchers performed a prospective, multicenter observational study of 1,343 patients with cirrhosis admitted to hospitals for more than 1 day because of complications from liver disease.

“ACLF is not defined at the present time,” researcher Rajiv Jalan, MD, professor of hepatology at the Institute of Liver and Digestive Health, UCL Medical School in London, said. “This syndrome is associated with organ failures and very high mortality, but there is no good prospective data, which leads to a lack of evidence-based definition, natural history [and] diagnostic criteria.”

The presence of acute-on-chronic liver failure (ACLF) was determined according to a high 28-day mortality rate and the development of organ failure (OF), as defined by a modified CLIF score: A 12-point scoring system assessing the liver, kidney and brain, plus coagulation, respiration and circulation.

Based on CLIF score, 32.9% of the study cohort experienced one or more OFs, with a mortality rate of 26.9% among these patients. Patients with no OF (n=901) had a 4.4% mortality rate, while patients experiencing a single, nonrenal OF with creatinine levels less than 1.5 mg/dL and no hepatic encephalopathy (n=139 patients) had a 6% mortality rate. Rates were higher among patients with renal failure than among those with single instances of nonrenal OF.

Researchers determined that patients do not have ACLF if they have experienced either no OF or one nonrenal incident of OF in the absence of hepatic encephalopathy and creatinine levels less than 1.5 mg/dL. Grade 1 ACLF was defined as renal failure or a single, nonrenal OF with hepatic encephalopathy of grade 1 or 2, or serum creatinine levels between 1.5 mg/dL and 2 mg/dL. Patients with two OF incidents were classified as grade 2, and those with three OFs or more as ACLF grade 3.

According to these criteria, ACLF occurred in 32% of the cohort, with an overall mortality rate of 33% at 28 days and 51% at 90 days. Patients without ACLF had a 28-day mortality rate of 1.9%, while those with ACLF had higher rates according to the number of OFs experienced: 23% with one OF, 31% with two and 74% with three or more. Factors associated with 28-day mortality in ACLF included CLIF score and leukocyte count, with increased leukocyte counts observed in patients with more advanced grades of ACLF.

ACLF developed without a precipitating event in 40% of cases, and without prior decompensation or less than 3 months after initial decompensation in 41% of cases. Jalan said patients with higher degrees of ACLF had more precipitating events than patients without ACLF, with bacterial infection and active alcoholism the most common. Both conditions were observed in less than 50% of the cohort.

“ACLF is common and occurs in about 30% of hospitalized cirrhotic patients,” Jalan said. “Organ failure characterizes this syndrome and is important in diagnosis and prognosis. … The ACLF classification accurately defines prognosis, and the syndrome is particularly severe in patients with no previous hepatic decompensation and those with high white cell counts. … We believe that acute-on-chronic liver failure is clinically, prognostically and pathophysiologically distinct, and has a very high mortality rate.”

Disclosure: The researchers report numerous financial disclosures.

For more information:

Jalan R. #113: Acute-on-Chronic Liver Failure (ACLF): A distinct clinical syndrome. Presented at: The Liver Meeting 2012; Nov. 9-13, Boston.