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

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Abstract

Background

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

Aim

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

Methods

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.

Results

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.

Conclusions

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.

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Abbreviations

ALD:

Alcoholic liver disease

ALF:

Acute liver failure

EV:

Esophageal varices

HBV:

Hepatitis B virus

HCC:

Hepatocellular carcinoma

HCUP:

Healthcare Cost and Utilization Project

HCV:

Hepatitis C virus

HE:

Hepatic encephalopathy

HRS:

Hepatorenal syndrome

NAFLD:

Nonalcoholic fatty liver disease

NIS:

National (Nationwide) Inpatient Sample

USD:

US dollar

References

  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.

    Article  PubMed  Google Scholar 

  2. Centers of Educational Expertise. The multidimensional burden of hepatic encephalopathy. 2012. http://www.chronicliverdisease.org/disease_focus/enewsletters/HepCoEE_eNewsLetter_Multidimensional_burden.pdf. Accessed April 03, 2018.

  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.

    Article  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  11. Montgomery JY, Bajaj JS. Advances in the evaluation and management of minimal hepatic encephalopathy. Curr Gastroenterol Rep. 2011;13:26–33.

    Article  PubMed  Google Scholar 

  12. Liere V, Sandhu G, DeMorrow S. Recent advances in hepatic encephalopathy. F1000Res. 2017;6:1637. https://doi.org/10.12688/f1000research.11938.1.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Basu PP, Shah NJ. Clinical and neurologic manifestation of minimal hepatic encephalopathy and overt hepatic encephalopathy. Clin Liver Dis. 2015;19:461–472.

    Article  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  17. Poordad FF. Review article: the burden of hepatic encephalopathy. Aliment Pharmacol Ther. 2006;25:3–9.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  19. Scott TR, Kronsten VT, Hughes RD, Shawcross DL. Pathophysiology of cerebral oedema in acute liver failure. World J Gastroenterol. 2013;19:9240–9255.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Flamm SL. Considerations for the cost-effective management of hepatic encephalopathy. Am J Manag Care. 2018;24:S51–S61.

    PubMed  Google Scholar 

  21. Healthcare Cost and Utilization Project (HCUP). Overview of the National (Nationwide) Inpatient Sample (NIS). https://www.hcup-us.ahrq.gov/nisoverview.jsp. Accessed January 04, 2018.

  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. https://www.hcup-us.ahrq.gov/db/nation%0A/nis/reports/NISRedesignFinalReport040914.pdf. Accessed February 06, 2018.

  23. Healthcare Cost and Utilization Project (HCUP). Trend weights for HCUP NIS data. https://www.hcup-us.ahrq.gov/db/nation/nis/trendwghts.jsp. Accessed February 06, 2018.

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  26. Elixhauser A, Steiner C, Harris DR, Coffey RM. Comorbidity measures for use with administrative data. Med Care. 1998;36:8–27.

    Article  CAS  PubMed  Google Scholar 

  27. Healthcare Cost and Utilization Project (HCUP). Elixhauser comorbidity software, version 3.7. https://www.hcup-us.ahrq.gov/toolssoftware/comorbidity/comorbidity.jsp. Accessed February 14, 2018.

  28. Bureau of Labor Statistics USD of L. CPI inflation calculator. http://www.bls.gov/data%0A/inflation_calculator.htm. Accessed January 31, 2018.

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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. https://doi.org/10.1038/s41395-018-0088-6.

    Article  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  36. Haut ER, Pronovost PJ, Schneider EB. Limitations of administrative databases. JAMA. 2012;307:2589.

    CAS  PubMed  Google Scholar 

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Funding

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

Author information

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Alameda Health System – Highland Hospital, 1411 East 31st Street, Highland Hospital – Highland Care Pavilion 5th Floor, Endoscopy Unit, Oakland, CA, 94602, USA

    Grishma Hirode & Robert J. Wong

  2. Department of Epidemiology and Biostatistics, University of California, San Francisco, 550 16th. Street, San Francisco, CA, 94158, USA

    Eric Vittinghoff

Authors
  1. Grishma Hirode
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  3. Robert J. Wong
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Contributions

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.

Corresponding author

Correspondence to Robert J. Wong.

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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.

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Hirode, G., Vittinghoff, E. & Wong, R.J. Increasing Burden of Hepatic Encephalopathy Among Hospitalized Adults: An Analysis of the 2010–2014 National Inpatient Sample. Dig Dis Sci 64, 1448–1457 (2019). https://doi.org/10.1007/s10620-019-05576-9

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