Increasing Burden of Hepatic Encephalopathy Among Hospitalized Adults: An Analysis of the 2010–2014 National Inpatient Sample

  • Grishma Hirode
  • Eric Vittinghoff
  • Robert J. WongEmail author
Original Article



Hepatic encephalopathy (HE) is associated with substantial morbidity and mortality, contributing significant burden on healthcare systems.


We aim to evaluate trends in clinical and economic burden of HE among hospitalized adults in the USA.


Using 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.


Among 142,860 hospitalizations with HE (mean age 59.3 years, 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.


The 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.


Hepatic encephalopathy Cirrhosis Acute liver failure Burden Mortality Charges Liver disease 



Alcoholic liver disease


Acute liver failure


Esophageal varices


Hepatitis B virus


Hepatocellular carcinoma


Healthcare Cost and Utilization Project


Hepatitis C virus


Hepatic encephalopathy


Hepatorenal syndrome


Nonalcoholic fatty liver disease


National (Nationwide) Inpatient Sample


US dollar


Author’s contribution

GH and RJW were involved in study concept and design. GH and RJW were involved in acquisition of data. GH, EV, and RJW were involved in analysis and interpretation of data and statistical analysis. GH and RJW drafted the manuscript. GH, EV, RJW critically revised the manuscript for important intellectual content. RJW was involved in study supervision. RJW had full access to all the data in the study and took responsibility for the integrity of the data and accuracy of the data analysis.


Robert Wong is supported by an AASLD Foundation Clinical and Translational Research Award in Liver Diseases.

Compliance with ethical standards

Conflict of interest

RJW receives research funding from Gilead Sciences and Abbvie, has served as a consultant and member of the advisory board for Gilead Sciences, and serves on the speaker’s bureau for Gilead Sciences, Salix, and Bayer. RJW is also funded by an AASLD Foundational Clinical and Translational Research Award in Liver Diseases. GH receives funding from Gilead Sciences. EV reports no conflicts of interest.

Supplementary material

10620_2019_5576_MOESM1_ESM.docx (30 kb)
Supplementary material 1 (DOCX 30 kb)


  1. 1.
    Vilstrup H, Amodio P, Bajaj J, et al. Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014;60:715–735.CrossRefGoogle Scholar
  2. 2.
    Centers of Educational Expertise. The multidimensional burden of hepatic encephalopathy. 2012. Accessed April 03, 2018.
  3. 3.
    Ferenci P, Lockwood A, Mullen K, et al. Hepatic encephalopathy—definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology. 2002;35:716–721.CrossRefGoogle Scholar
  4. 4.
    Stepanova M, Mishra A, Venkatesan C, Younossi ZM. In-hospital mortality and economic burden associated with hepatic encephalopathy in the United States From 2005 to 2009. Clin Gastroenterol Hepatol. 2012;10:1034–1041.CrossRefGoogle Scholar
  5. 5.
    Wong RJ, Gish RG, Ahmed A. Hepatic encephalopathy is associated with significantly increased mortality among patients awaiting liver transplantation. Liver Transplant. 2014;20:1454–1461.CrossRefGoogle Scholar
  6. 6.
    Udayakumar N, Subramaniam K, Umashankar L, Verghese J, Jayanthi V. Predictors of mortality in hepatic encephalopathy in acute and chronic liver disease: a preliminary observation. J Clin Gastroenterol. 2007;41:922–926.CrossRefGoogle Scholar
  7. 7.
    Findlay JY, Fix OK, Paugam-Burtz C, et al. Critical care of the end-stage liver disease patient awaiting liver transplantation. Liver Transplant. 2011;17:496–510.CrossRefGoogle Scholar
  8. 8.
    Bustamante J, Rimola A, Ventura P-J, et al. Prognostic significance of hepatic encephalopathy in patients with cirrhosis. J Hepatol. 2015;30:890–895.CrossRefGoogle Scholar
  9. 9.
    Amodio P, Del Piccolo F, Pettenò E, et al. Prevalence and prognostic value of quantified electroencephalogram (EEG) alterations in cirrhotic patients. J Hepatol. 2001;35:37–45.CrossRefGoogle Scholar
  10. 10.
    Romero-Gómez M, Boza F, García-Valdecasas MS, García E, Aguilar-Reina J. Subclinical hepatic encephalopathy predicts the development of overt hepatic encephalopathy. Am J Gastroenterol. 2001;96:2718–2723.CrossRefGoogle Scholar
  11. 11.
    Montgomery JY, Bajaj JS. Advances in the evaluation and management of minimal hepatic encephalopathy. Curr Gastroenterol Rep. 2011;13:26–33.CrossRefGoogle Scholar
  12. 12.
    Liere V, Sandhu G, DeMorrow S. Recent advances in hepatic encephalopathy. F1000Res. 2017;6:1637. Scholar
  13. 13.
    Basu PP, Shah NJ. Clinical and neurologic manifestation of minimal hepatic encephalopathy and overt hepatic encephalopathy. Clin Liver Dis. 2015;19:461–472.CrossRefGoogle Scholar
  14. 14.
    Scaglione SJ, Metcalfe L, Kliethermes S, et al. Early hospital readmissions and mortality in patients with decompensated cirrhosis enrolled in a large National Health Insurance Administrative Database. J Clin Gastroenterol. 2017;51:839–844.Google Scholar
  15. 15.
    Bajaj JS, Reddy R, Tandon P, et al. The 3-month readmission rate remains unacceptably high in a large North American cohort of cirrhotic patients. Hepatology. 2016;64:200–208.CrossRefGoogle Scholar
  16. 16.
    Tapper EB, Finkelstein D, Mittleman MA, Piatkowski G, Chang M, Lai M. A quality improvement initiative decreases 30-day readmission rates for patients with cirrhosis: a prospective trial. Clin Gastroenterol Hepatol. 2016;14:753–759.CrossRefGoogle Scholar
  17. 17.
    Poordad FF. Review article: the burden of hepatic encephalopathy. Aliment Pharmacol Ther. 2006;25:3–9.CrossRefGoogle Scholar
  18. 18.
    Nguyen GC, Segev DL, Thuluvath PJ. Nationwide increase in hospitalizations and hepatitis C among inpatients with cirrhosis and sequelae of portal hypertension. Clin Gastroenterol Hepatol. 2007;5:1092–1099.CrossRefGoogle Scholar
  19. 19.
    Scott TR, Kronsten VT, Hughes RD, Shawcross DL. Pathophysiology of cerebral oedema in acute liver failure. World J Gastroenterol. 2013;19:9240–9255.CrossRefGoogle Scholar
  20. 20.
    Flamm SL. Considerations for the cost-effective management of hepatic encephalopathy. Am J Manag Care. 2018;24:S51–S61.Google Scholar
  21. 21.
    Healthcare Cost and Utilization Project (HCUP). Overview of the National (Nationwide) Inpatient Sample (NIS). Accessed January 04, 2018.
  22. 22.
    Houchens RL, Ross DN, Elixhauser A, Jiang J. Nationwide Inpatient Sample redesign: final report. HCUP NIS Related Reports ONLINE. U.S. Agency for Healthcare Research and Quality. 2014. Accessed February 06, 2018.
  23. 23.
    Healthcare Cost and Utilization Project (HCUP). Trend weights for HCUP NIS data. Accessed February 06, 2018.
  24. 24.
    Mellinger JL, Richardson CR, Mathur AK, Volk ML. Variation among United States hospitals in inpatient mortality for cirrhosis. Clin Gastroenterol Hepatol. 2015;13:577–584.CrossRefGoogle Scholar
  25. 25.
    Asrani SK, Kouznetsova M, Ogola G, et al. Increasing health care burden of chronic liver disease compared with other chronic diseases, 2004–2013. Gastroenterology. 2018;155:719–729.CrossRefGoogle Scholar
  26. 26.
    Elixhauser A, Steiner C, Harris DR, Coffey RM. Comorbidity measures for use with administrative data. Med Care. 1998;36:8–27.CrossRefGoogle Scholar
  27. 27.
    Healthcare Cost and Utilization Project (HCUP). Elixhauser comorbidity software, version 3.7. Accessed February 14, 2018.
  28. 28.
    Bureau of Labor Statistics USD of L. CPI inflation calculator. Accessed January 31, 2018.
  29. 29.
    Henry AJ, Hevelone ND, Lipsitz S, Nguyen LL. Comparative methods for handling missing data in large databases. J Vasc Surg. 2013;58:1353–1359.CrossRefGoogle Scholar
  30. 30.
    Moore CG, Lipsitz SR, Addy CL, Hussey JR, Fitzmaurice G, Natarajan S. Logistic regression with incomplete covariate data in complex survey sampling: application of reweighted estimating equations. Epidemiology. 2009;20:382–390.CrossRefGoogle Scholar
  31. 31.
    Asrani SK, Larson JJ, Yawn B, Therneau TM, Kim WR. Underestimation of liver-related mortality in the United States. Gastroenterology. 2013;145:375–382.CrossRefGoogle Scholar
  32. 32.
    Kim Y, Ejaz A, Tayal A, et al. Temporal trends in population-based death rates associated with chronic liver disease and liver cancer in the United States over the last 30 years. Cancer. 2009;120:3058–3065.CrossRefGoogle Scholar
  33. 33.
    Goldberg D, Ditah IC, Saeian K, et al. Changes in the prevalence of hepatitis C virus infection, nonalcoholic steatohepatitis, and alcoholic liver disease among patients with cirrhosis or liver failure on the waitlist for liver transplantation. Gastroeneterology. 2017;152:1090–1099.CrossRefGoogle Scholar
  34. 34.
    Noureddin M, Vipani A, Bresee C, et al. NASH leading cause of liver transplant in women: updated analysis of indications for liver transplant and ethnic and gender variances. Am J Gastroenterol. 2018;113:1649–1659. Scholar
  35. 35.
    Younk K, Liu B, Bhuket T, et al. Long-term trends in chronic hepatitis B virus infection associated liver transplantation outcomes in the United States. J Viral Hepat. 2017;24:789–796.CrossRefGoogle Scholar
  36. 36.
    Haut ER, Pronovost PJ, Schneider EB. Limitations of administrative databases. JAMA. 2012;307:2589.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Gastroenterology and HepatologyAlameda Health System – Highland HospitalOaklandUSA
  2. 2.Department of Epidemiology and BiostatisticsUniversity of California, San FranciscoSan FranciscoUSA

Personalised recommendations