ABSTRACT & COMMENTARY
Acute on Chronic Liver Failure: New Definition and Implications
By Deborah J. DeWaay, MD, FACP
Assistant Professor, Medical University of South Carolina, Charleston, SC
Dr. DeWaay reports no financial relationships in this field of study
SYNOPSIS: Acute on chronic liver failure is a distinct clinical entity marked by systemic inflammation, organ failure and high mortality.
Source: Moreau R, Arroyo V. Acute on Chronic Liver Failure: A New Clinical Entity. Clinical Gastroenterology and Hepatology. 2014. ePub ahead of print.
Ascites, gastrointestinal hemorrhage, hepatic encephalopathy and bacterial infections are common complications experienced by patients with cirrhosis. Traditionally, when a cirrhotic patient experiences one of these complications and develops worsening liver function, he or she is diagnosed with acute on chronic liver failure. The mortality of these patients is very high. However, up until 2013, there was no evidence-based definition of acute on chronic liver failure, only expert opinion. The European Association for the Study of the Liver/Chronic Liver Failure Consortium (EASL-CLIF Consortium) performed the CLIF Acute on Chronic Liver Failure in Cirrhosis (CANONIC) study with the purpose of defining acute on chronic liver failure (ACLF). This study is a prospective, observational, and multicenter study.
The study enrolled 1343 cirrhotic patients who were hospitalized for at least one day for one or more of the following: hepatic encephalopathy, large-volume ascites, bacterial infection, or gastrointestinal hemorrhage. The patients were assessed for organ failure; the number and degree of organ failure was used to grade the degree of acute on chronic liver failure, and determine the associated transplant-free mortality rates. Liver failure was considered a bilirubin of 12.0 mg/dL or more. Kidney failure was the requirement of renal replacement therapy or a creatinine of greater than 2.0 mg/dL. Coagulation failure was defined as an INR of more than 2.5 or platelets of 20,000/microL or less. Circulatory failure was defined as the use of vasopressor support to maintain blood pressure. Cerebral failure was defined as grade 3 or 4 hepatic encephalopathy. Lastly, respiratory failure was present when the partial pressure of arterial oxygen to the FiO2 was 200 or less.
The patients were divided into four groups: no ACLF and ACLF grades 1-3. No ACLF was defined as no organ failure, or single organ failure without kidney dysfunction or hepatic encephalopathy. Grade 1 ACLF was single organ failure with a creatinine of 1.5-1.9mg/dL and/or hepatic encephalopathy grade 1 or 2. Grade 2 and 3 ACLF were defined as two-organ and three-organ failures respectively.
The 28-day transplant free mortality rate of each group rose with increasing in organ dysfunction: no ACLF 4.7%, ACLF grade 1 22.1%, grade 2 32.0%, grade 3 78.6%. Patients with ACLF were slightly younger, 56 years old compared to 58 years old (P = 0.02). They were significantly more likely to have alcoholic cirrhosis and be active alcoholics, but were less likely to have cirrhosis from hepatitis C. In almost half of the ACLF patients, no precipitating event was identified. In those that did have an event, infection in general and from spontaneous bacterial peritonitis and pneumonia specifically were significantly more common in the ACLF group than the no-ACLF group. In addition, the ACLF group had higher plasma C-reactive proteins (CRP) compared to those with no ACLF, 39.9mg/L vs. 25.4mg/L respectively (P = <0.001). Interestingly, ACLF is not the same as end-stage cirrhosis, as 23.2% of patients developed ACLF without any previous history of acute decompensated cirrhosis; 17.6% of ACLF patients developed it within <3 months of their first episode of decompensation, which was significantly higher than the 10.8% of those with no ACLF (P = 0.02).
Lastly, the authors divided the patients into three groups irrespective of ACLF: nonalcoholic cirrhosis, alcoholic cirrhosis without active alcohol consumption and alcoholic cirrhosis with active alcohol consumption. The group with active alcohol consumption was significantly younger, more likely to have ACLF, a higher white cell count, bilirubin, INR and AST when compared to the other two groups. There was no significant difference between the nonalcoholic cirrhosis and alcoholic cirrhosis without active alcohol consumption groups in these areas. In conclusion, the authors argue that ACLF is a new clinical entity from traditional decompensated cirrhosis that is marked by younger age, organ failure, high mortality and systemic inflammation, which includes subcategories such as severe alcoholic hepatitis and severe sepsis.
The defining of acute on chronic liver failure as a new clinical entity is important for hospitalists for several reasons. First, although a subspecialist will certainly be involved in the care of these patients at most institutions, the hospitalist will be integral to the discussion with the patient and family regarding discussions of prognosis. It is crucial that hospitalists understand the high mortality among patients with acute on chronic liver failure. Second, the study highlights that acute on chronic liver failure is not necessarily equivalent to the end stages of cirrhosis and can happen at any time during the disease. In this study, almost half of the ACLF patients experienced this complication without ever having an episode of decompensation or within 3 months of their first episode of decompensation. Lastly, I think the differences in patients with alcoholic cirrhosis with and without active alcohol intake is significant. The patients without active alcohol intake had a lower 28-day mortality and less acute on chronic liver failure. Although these findings are intuitive, they should motivate hospitalists to get patients with alcoholic cirrhosis into alcohol rehabilitation treatment since it is literally life or death for the patient.