Understanding Acute-on-Chronic Liver Failure

Rowen K. Zetterman, MD


January 19, 2016

In This Article

A Host of Complications With Considerable Cost

Patients who develop cirrhosis may remain asymptomatic during the early stages of advanced disease (compensated cirrhosis), with no clinical evidence of ascites, esophagogastric varices, or overt encephalopathy. As disease progression reduces hepatic reserve, however, increased portal hypertension may lead to hepatic decompensation. Complications such as infection, gastrointestinal bleeding, or hepatocellular carcinoma may accelerate clinical decompensation.[1] As many as 15% of patients with compensated cirrhosis develop clinical decompensation each year. While some patients recover clinically from acute hepatic decompensation following a precipitating event, one third or more will progress to additional single or multiple organ failure.[2]

Acute hepatic decompensation with ascites, encephalopathy, or gastrointestinal bleeding associated with organ failure such as renal or hepatic failure is now considered acute-on-chronic liver failure (ACLF),[3] a term first suggested in 1995.[4] ACLF can result from acute complications such as sepsis, spontaneous bacterial peritonitis, or gastrointestinal bleeding or from superimposed events such as acute viral hepatitis, drug-induced liver injury, alcohol consumption, or ischemic hepatitis.[5] In China, 70% of cases of acute-on-chronic liver injury result from reactivation of chronic hepatitis B virus (HBV) infection.[6] The likelihood of death is high with ACLF,[7] with patient care costs ranging from $116,000 to $180,000 per episode at a total cost of more than $3 billion annually.[8]

ACLF can also develop in patients awaiting liver transplantation.[9] Mortality on the wait list for patients with ACLF is greater than 50%, with only 25% of patients successfully transplanted. Multiorgan failure is the most common cause of death in those with ACLF awaiting transplantation.

But when we admit a patient with advanced liver disease, how can we identify if they are at risk for ACLF? While a higher Model for End-Stage Liver Disease (MELD) score indicates reduced hepatic reserve, it may not identify those who will develop ACLF. Is every patient at risk following a precipitating event such as infection or gastrointestinal bleeding? Can we use an admission assessment of patient "frailty"? A combination of an activities of daily living score coupled with the Braden Scale to assess frailty does appear to correlate with 90-day mortality in patients admitted with hepatic decompensation.[10]


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