BackgroundHepatic encephalopathy (HE) is associated with substantial morbidity and mortality, contributing significant burden on healthcare systems.AimWe aim to evaluate trends in clinical and economic burden of HE among hospitalized adults in the USA.MethodsUsing the 2010-2014 National Inpatient Sample, we identified adults hospitalized with HE using ICD-9-CM codes. Annual trends in hospitalizations with HE, in-hospital mortality, and hospital charges were stratified by the presence of acute liver failure (ALF) or cirrhosis. Adjusted multivariable regression models were evaluated for predictors of in-hospital mortality and hospitalization charges.ResultsAmong 142,860 hospitalizations with HE (mean age 59.3years, 57.8% male), 67.7% had cirrhosis and 3.9% ALF. From 2010 to 2014, total number of hospitalizations with HE increased by 24.4% (25,059 in 2010 to 31,182 in 2014, p<0.001). Similar increases were seen when stratified by ALF (29.7% increase) and cirrhosis (29.7% increase). Overall in-hospital mortality decreased from 13.4% (2010) to 12.3% (2014) (p=0.001), with similar decreases observed in ALF and cirrhosis. Total inpatient charges increased by 46.0% ($8.15 billion, 2010 to $11.9 billion, 2014). On multivariable analyses, ALF was associated with significantly higher odds of in-hospital mortality (OR 5.37; 95%CI 4.97-5.80; p<0.001) as well as higher mean inpatient charges (122.6% higher; 95% CI +115.0-130.3%; p<0.001) compared to cirrhosis. The presence of ascites, hepatocellular carcinoma, and hepatorenal syndrome was associated with increased mortality.ConclusionsThe clinical and economic burden of hospitalizations with HE in the USA continues to rise. In 2014, estimated national economic burden of hospitalizations with HE reached $11.9 billion.