Acute on chronic liver failure (ACLF) is associated with multisystem organ failure and poor prognosis in hospitalized patients with cirrhosis. We aimed to determine time trends in the epidemiology, economic burden, and mortality of ACLF in the United States. The National Inpatient Sample database was queried between 2001 and 2011. ACLF was defined as two or more extrahepatic organ failures in patients with cirrhosis. The primary outcomes were trends in hospitalizations, hospital costs, and inpatient mortality. The number of hospitalizations for cirrhosis in the United States nearly doubled from 371,000 in 2001 to 659,000 in 2011. The prevalence of ACLF among those hospitalizations increased from 1.5% (n = 5,400) to 5% (n = 32,300). The inpatient costs increased 2-fold for cirrhosis ($4.8 billion to $9.8 billion) and 5-fold ($320 million to $1.7 billion) for ACLF. In 2011, the cost per hospitalization for ACLF was 3.5-fold higher than that for cirrhosis ($53,570 versus $15,193). The in-hospital fatality rates decreased from 65% to 50% for ACLF and from 10% to 7% for cirrhosis. The organ failure trends in ACLF showed an increasing proportion of cardiovascular and cerebral and decreasing proportion of respiratory and renal failure. Age, male sex, and the number and types of organ failure were predictors of death in ACLF. Conclusion: Cirrhosis and ACLF represent a substantial and increasing health and economic burden in the United States; these data highlight an urgent need for research on pathophysiological mechanisms and effective therapy as well as for education of health care providers of its importance in the care of patients with cirrhosis. (Hepatology 2016;64:2165-2172).
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