The Use of Administrative Data to Investigate the Population Burden of Hepatic Encephalopathy
Abstract
:1. Introduction
2. Identifying Cirrhosis with Administrative Data
3. Identifying Hepatic Encephalopathy with Administrative Data
4. Administrative Databases: Which to Use
4.1. US Data
4.2. International Data
5. Identifying Risk Factors for Hepatic Encephalopathy
6. Outcomes of HE
7. Pitfalls of Administrative Data
8. Future Directions
9. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Beste, L.A.; Leipertz, S.L.; Green, P.K.; Dominitz, J.A.; Ross, D.; Ioannou, G.N. Trends in burden of cirrhosis and hepatocellular carcinoma by underlying liver disease in US veterans, 2001–2013. Gastroenterology 2015, 149, 1471–1482. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tapper, E.B.; Parikh, N.D. Mortality due to cirrhosis and liver cancer in the United States, 1999–2016: Observational study. BMJ 2018, 362, k2817. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tapper, E.B.; Halbert, B.; Mellinger, J. Rates of and reasons for hospital readmissions in patients with cirrhosis: A multistate population-based cohort study. Clin. Gastroenterol. Hepatol. 2016, 14, 1181–1188. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tapper, E.B.; Kanwal, F.; Asrani, S.K.; Ho, C.; Ovchinsky, N.; Poterucha, J.; Flores, A.; Smith, J.E.; Ankoma-Sey, V.; Luxon, B.; et al. Patient reported outcomes in cirrhosis: A scoping review of the literature. Hepatology 2017, 67, 2375–2383. [Google Scholar] [CrossRef] [Green Version]
- Jepsen, P.; Ott, P.; Andersen, P.K.; Sørensen, H.T.; Vilstrup, H. Clinical course of alcoholic liver cirrhosis: A Danish population-based cohort study. Hepatology 2009, 51, 1675–1682. [Google Scholar] [CrossRef]
- Vilstrup, H.; Amodio, P.; Bajaj, J.; Cordoba, J.; Ferenci, P.; Mullen, K.D.; Weissenborn, K.; Wong, P. 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, 715–773. [Google Scholar] [CrossRef]
- Re, V.L.; Lim, J.K.; Goetz, M.B.; Tate, J.; Bathulapalli, H.; Klein, M.B.; Rimland, D.; Rodriguez-Barradas, M.C.; Butt, A.A.; Gibert, C.L.; et al. Validity of diagnostic codes and liver-related laboratory abnormalities to identify hepatic decompensation events in the Veterans Aging Cohort Study. Pharmacoepidemiol. Drug Saf. 2011, 20, 689–699. [Google Scholar] [CrossRef]
- Kramer, J.R.; Davila, J.A.; Miller, E.D.; Richardson, P.; Giordano, T.P.; El-Serag, H.B. The validity of viral hepatitis and chronic liver disease diagnoses in Veterans Affairs administrative databases. Aliment. Pharmacol. Ther. 2007, 27, 274–282. [Google Scholar] [CrossRef]
- Ramrakhiani, N.S.; Le, M.; Yeo, Y.H.; Le, A.; Maeda, M.; Nguyen, M.H. Validity of international classification of diseases, 10th revision, codes for cirrhosis. Dig. Dis. 2020. [Google Scholar] [CrossRef]
- Goldberg, D.S.; Lewis, J.; Halpern, S.; Weiner, M.; Re, V.L. Validation of three coding algorithms to identify patients with end-stage liver disease in an administrative database. Pharmacoepidemiol. Drug Saf. 2012, 21, 765–769. [Google Scholar] [CrossRef] [Green Version]
- Nehra, M.S.; Ma, Y.; Clark, C.; Amarasingham, R.; Rockey, D.C.; Singal, A.G. Use of administrative claims data for identifying patients with cirrhosis. J. Clin. Gastroenterol. 2013, 47, e50–e54. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lapointe-Shaw, L.; Georgie, F.; Carlone, D.; Cerocchi, O.; Chung, H.; Dewit, Y.; Feld, J.J.; Holder, L.; Kwong, J.C.; Sander, B.; et al. Identifying cirrhosis, decompensated cirrhosis and hepatocellular carcinoma in health administrative data: A validation study. PLoS ONE 2018, 13, e0201120. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mapakshi, S.; Kramer, J.R.; Richardson, P.; El-Serag, H.B.; Kanwal, F. Positive predictive value of international classification of diseases, 10th revision, codes for cirrhosis and its related complications. Clin. Gastroenterol. Hepatol. 2018, 16, 1677–1678. [Google Scholar] [CrossRef] [PubMed]
- Corey, K.E.; Kartoun, U.; Zheng, H.; Shaw, S.Y. Development and validation of an algorithm to identify nonalcoholic fatty liver disease in the electronic medical record. Dig. Dis. Sci. 2015, 61, 913–919. [Google Scholar] [CrossRef]
- Kanwal, F.; Kramer, J.R.; Buchanan, P.; Asch, S.M.; Assioun, Y.; Bacon, B.R.; Li, J.; El–Serag, H.B. The quality of care provided to patients with cirrhosis and ascites in the Department of Veterans Affairs. Gastroenterology 2012, 143, 70–77. [Google Scholar] [CrossRef] [PubMed]
- Kaplan, D.E.; Dai, F.; Aytaman, A.; Baytarian, M.; Fox, R.; Hunt, K.; Knott, A.; Pedrosa, M.; Pocha, C.; Mehta, R.; et al. Development and performance of an algorithm to estimate the Child-Turcotte-Pugh Score from a national electronic healthcare database. Clin. Gastroenterol. Hepatol. 2015, 13, 2333–2341. [Google Scholar] [CrossRef] [Green Version]
- Tapper, E.B.; Korovaichuk, S.; Baki, J.; Williams, S.; Nikirk, S.; Waljee, A.K.; Parikh, N.D. Identifying patients with hepatic encephalopathy using administrative data in the ICD-10 era. Clin. Gastroenterol. Hepatol. 2019. [Google Scholar] [CrossRef]
- Driver, R.J.; Balachandrakumar, V.; Burton, A.; Shearer, J.; Downing, A.; Cross, T.; Morris, E.; A Rowe, I. Validation of an algorithm using inpatient electronic health records to determine the presence and severity of cirrhosis in patients with hepatocellular carcinoma in England: An observational study. BMJ Open 2019, 9, e028571. [Google Scholar] [CrossRef]
- Thygesen, S.K.; Christiansen, C.F.; Christensen, S.; Lash, T.L.; Sørensen, H.T. The predictive value of ICD-10 diagnostic coding used to assess Charlson comorbidity index conditions in the population-based Danish National Registry of Patients. BMC Med Res. Methodol. 2011, 11, 83. [Google Scholar] [CrossRef] [Green Version]
- Moon, A.M.; Singal, A.G.; Tapper, E.B. Contemporary epidemiology of chronic liver disease and cirrhosis. Clin. Gastroenterol. Hepatol. 2020, 18, 2650–2666. [Google Scholar] [CrossRef]
- Rosenblatt, R.; Shen, N.; Tafesh, Z.; Cohen-Mekelburg, S.; Crawford, C.V.; Kumar, S.; Lucero, C.; Brown, R.S.; Jesudian, A.; Fortune, B.E. The North American Consortium for the study of end-stage liver disease—Acute-on-chronic liver failure score accurately predicts survival: An external validation using a national cohort. Liver Transplant. 2020, 26, 187–195. [Google Scholar] [CrossRef] [PubMed]
- Rakoski, M.O.; McCammon, R.J.; Piette, J.D.; Iwashyna, T.J.; Marrero, J.A.; Lok, A.S.; Langa, K.; Volk, M.L. Burden of cirrhosis on older Americans and their families: Analysis of the health and retirement study. Hepatology 2011, 55, 184–191. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mellinger, J.L.; Shedden, K.; Winder, G.S.; Tapper, E.; Adams, M.; Fontana, R.J.; Volk, M.L.; Blow, F.C.; Lok, A.S. The high burden of alcoholic cirrhosis in privately insured persons in the United States. Hepatology 2018, 68, 872–882. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Scaglione, S.J.; Metcalfe, L.; Kliethermes, S.A.; Vasilyev, I.; Tsang, R.; Caines, A.; Mumtaz, S.; Goyal, V.; Khalid, A.; Shoham, D.; 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] [CrossRef]
- Tapper, E.B.; Aberasturi, D.; Zhao, Z.; Hsu, C.-Y.; Parikh, N.D. Outcomes after hepatic encephalopathy in population-based cohorts of patients with cirrhosis. Aliment. Pharmacol. Ther. 2020, 51, 1397–1405. [Google Scholar] [CrossRef]
- Flemming, J.A.; Dewit, Y.; Mah, J.M.; Saperia, J.; A Groome, P.; Booth, C.M. Incidence of cirrhosis in young birth cohorts in Canada from 1997 to 2016: A retrospective population-based study. Lancet Gastroenterol. Hepatology 2019, 4, 217–226. [Google Scholar] [CrossRef]
- Vestberg, K.; Thulstrup, A.M.; Sørensen, H.T.; Ottesen, P.; Sabroe, S.; Vilstrup, H. Data quality of administratively collected hospital discharge data for liver cirrhosis epidemiology. J. Med. Syst. 1997, 21, 11–20. [Google Scholar] [CrossRef]
- Jepsen, P.; Vilstrup, H.; Andersen, P.K.; Sørensen, H.T. Socioeconomic status and survival of cirrhosis patients: A Danish nationwide cohort study. BMC Gastroenterol. 2009, 9, 35. [Google Scholar] [CrossRef] [Green Version]
- Askgaard, G.; Leon, D.A.; Kjaer, M.S.; Deleuran, T.; Gerds, T.A.; Tolstrup, J.S. Risk for alcoholic liver cirrhosis after an initial hospital contact with alcohol problems: A nationwide prospective cohort study. Hepatology 2017, 65, 929–937. [Google Scholar] [CrossRef] [Green Version]
- Hallager, S.; Brehm Christensen, P.; Ladelund, S.; Rye Clausen, M.; Lund Laursen, A.; Møller, A.; Schlicthting, P.; Galmstrup Madsen, L.; Gerstoft, J.; Lunding, S.; et al. Mortality rates in patients with chronic hepatitis C and cirrhosis compared with the general population: A Danish cohort study. J. Infect. Dis. 2017, 215, 192–201. [Google Scholar]
- Nilsson, E.; Anderson, H.; Sargenti, K.; Lindgren, S.; Prytz, H. Incidence, clinical presentation and mortality of liver cirrhosis in Southern Sweden: A 10-year population-based study. Aliment. Pharmacol. Ther. 2016, 43, 1330–1339. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nilsson, E.; Anderson, H.; Sargenti, K.; Lindgren, S.; Prytz, H. Clinical course and mortality by etiology of liver cirrhosis in Sweden: A population based, long-term follow-up study of 1317 patients. Aliment. Pharmacol. Ther. 2019, 49, 1421–1430. [Google Scholar] [CrossRef] [PubMed]
- Nilsson, E.; Anderson, H.; Sargenti, K.; Lindgren, S.; Prytz, H. Patients with liver cirrhosis show worse survival if decompensation occurs later during course of disease than at diagnosis. Scand. J. Gastroenterol. 2018, 53, 475–481. [Google Scholar] [CrossRef] [PubMed]
- Nilsson, E.; Anderson, H.; Sargenti, K.; Lindgren, S.; Prytz, H. Risk and outcome of hepatocellular carcinoma in liver cirrhosis in Southern Sweden: A population-based study. Scand. J. Gastroenterol. 2019, 54, 1027–1032. [Google Scholar] [CrossRef] [PubMed]
- Bengtsson, B.; Askling, J.; Ludvigsson, J.F.; Hagström, H. Validity of administrative codes associated with cirrhosis in Sweden. Scand. J. Gastroenterol. 2020, 1–6. [Google Scholar] [CrossRef]
- Sung, K.-C.; Kim, B.-S.; Cho, Y.K.; Park, D.I.; Woo, S.; Kim, S.; Wild, S.; Byrne, C.D. Predicting incident fatty liver using simple cardio-metabolic risk factors at baseline. BMC Gastroenterol. 2012, 12, 84. [Google Scholar] [CrossRef] [Green Version]
- Isenhour, C.; Hariri, S.; Vellozzi, C. Monitoring the hepatitis C care cascade using administrative claims data. Am. J. Manag. Care 2018, 24, 232–238. [Google Scholar]
- Niu, B.; A Forde, K.; Goldberg, D.S. Coding algorithms for identifying patients with cirrhosis and hepatitis B or C virus using administrative data. Pharmacoepidemiol. Drug Saf. 2015, 24, 107–111. [Google Scholar] [CrossRef]
- Sheu, M.-J.; Liang, F.-W.; Li, S.-T.; Li, C.-Y.; Lu, T.-H. Validity of ICD-10-CM codes used to identify patients with chronic hepatitis B and C virus infection in administrative claims data from the Taiwan National Health Insurance outpatient claims dataset. Clin. Epidemiol. 2020, 12, 185–192. [Google Scholar] [CrossRef] [Green Version]
- Tapper, E.B.; Henderson, J.B.; Parikh, N.D.; Ioannou, G.N.; Lok, A.S. Incidence of and risk factors for hepatic encephalopathy in a population-based cohort of Americans with cirrhosis. Hepatol. Commun. 2019, 3, 1510–1519. [Google Scholar] [CrossRef] [Green Version]
- Tapper, E.B.; Parikh, N.D.; Sengupta, N.; Mellinger, J.; Ratz, D.; Lok, A.S.; Su, G.L. A risk score to predict the development of hepatic encephalopathy in a population-based cohort of patients with cirrhosis. Hepatology 2018, 68, 1498–1507. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wong, R.J.; Gish, R.; Ahmed, A. Hepatic encephalopathy is associated with significantly increased mortality among patients awaiting liver transplantation. Liver Transplant. 2014, 20, 1454–1461. [Google Scholar] [CrossRef] [PubMed]
- 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. 2019, 64, 1448–1457. [Google Scholar] [CrossRef] [PubMed]
- Stepanova, M.; Mishra, A.; Venkatesan, C.; Younossi, Z.M. 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. [Google Scholar] [CrossRef]
- Roggeri, D.P.; Roggeri, A.; Rossi, E.; Cinconze, E.; Gasbarrini, A.; Preti, P.M.; De Rosa, M. Overt hepatic encephalopathy in Italy: Clinical outcomes and healthcare costs. Hepatic Med. Evid. Res. 2015, 7, 37–42. [Google Scholar] [CrossRef] [Green Version]
- Chang, E.K.; Yu, C.Y.; Clarke, R.; Hackbarth, A.; Sanders, T.; Esrailian, E.; Hommes, D.W.; Runyon, B.A. Defining a Patient Population with Cirrhosis. J. Clin. Gastroenterol. 2016, 50, 889–894. [Google Scholar] [CrossRef]
Tool | Description | Study | Database | Relevant Result | Validated Method for Identifying HE or Cirrhosis | Limitations | Benefits |
---|---|---|---|---|---|---|---|
International Classification of Diseases, 9th Revision (ICD-9) |
| V. Lo Re et al. (2011) |
| Nine of 295 patients with an ICD-9 code or laboratory value indicating liver dysfunction had an ICD-9 code for HE; the PPV of this code was 0.11 and estimated NPV of 0.99 | HE | ICD-9 is not being coded in the United States after 2015, so available data ranges are limited; Variable accuracy in coding | International; Currently best validated; Specific code for HE |
Goldberg et al. (2012) |
| Presence of one inpatient or outpatient ICD-9 code for cirrhosis, chronic liver disease, and a hepatic decompensation (of which HE was one), the PPV of 0.85 for confirmed cirrhosis | Cirrhosis | ||||
Kanwal et al. (2012) |
| After identifying cirrhosis patients with ICD-9 codes and laboratory data, at least one ICD-9 code for HE had PPV of 0.86 and NPV of 0.87 for confirmed HE | HE | ||||
Nehra et al. (2013) |
| ICD-9 code for HE had PPV 0.92 and NPV 0.36 for identifying confirmed cirrhosis; did not report if it identified HE | Cirrhosis | ||||
Lapointe-Shaw et al. (2018) |
| Having a single hospital diagnostic code for cirrhosis, including 572.2, was specific for cirrhosis (0.91–0.96 depending on subcohort), but not as sensitive (0.57–0.77); however, the authors did not specify in how many cases 572.2 was used vs. other codes | Cirrhosis | ||||
International Classification of Diseases, 10th Revision (ICD-10) |
| Thygesen et al. (2011) |
| The PPV of one inpatient or outpatient ICD-10 code for moderate/severe liver disease, which included K72.90, correctly identifying cirrhosis was 1.00; however, the authors did not specify in how many cases K72.90 was used vs. other codes | Cirrhosis | Only available in the United States 2015 and thereafter | International; Required to use data after 2015 in the United States; Readily available in most databases |
Mapakshi et al. (2018) |
| Unable to validate the use of ICD-10 codes for HE because there were no HE events during the study period | Neither | ||||
Tapper et al. (2020) |
| In a validation cohort of veterans with HCV, ICD-10 code K72.90 identified development of HE with PPV 0.90 and NPV 0.93 | HE | ||||
Lapointe-Shaw et al. (2018) |
| Having a single hospital diagnostic code for cirrhosis, including K72.90, was specific for cirrhosis (0.91–0.96 depending on subcohort), but not as sensitive (0.57–0.77); however, the authors did not specify in how many cases K72.90 was used vs. other codes | Cirrhosis | ||||
Prescription Data |
| Tapper et al. (2020) |
| In a validation cohort of veterans with HCV, lactulose prescription had PPV of 0.73 and NPV of 0.99 for HE diagnosis, while lactulose or rifaximin prescription had a PPV of 0.71 and NPV of 0.99 | HE | Not available in every database | Lactulose therapy for overt HE is nearly uniform |
Combination |
| Kaplan et al. (2015) |
| An algorithm based on the ICD-9 code for HE and prescription fills for lactulose or rifaximin had weighted kappa agreement of 0.51 with the CTP-subscore for HE | HE | Not available in every database | Using multiple modalities in one algorithm can enhance predictive value |
Data Sources | Population | Data Elements | Outcomes | Validated Definition of Cirrhosis | Validated Definition of HE | Limitations |
---|---|---|---|---|---|---|
Veterans Affairs (VA) | National health care for US veterans | ICD-9/10CPT Physical exam Pharmacy Laboratory Imaging |
| Kanwal et al. (2012) V. Lo Re et al. (2011) | Kanwal et al. (2012) Kaplan et al. (2015) Tapper et al. (2020) | Male Missing outside data VA population and access to care may differ |
Medicare | United States ≥65 years old | ICD-9/10CPT Pharmacy |
| Rakoski et al. (2012) | None | No laboratory data Relies on diagnosis and procedure codes |
National Inpatient Sample (NIS) / National Readmissions Database (NRD) | United States Nationally representative sample All payers | ICD-9CPT |
| None | None | No laboratory data available Relies on diagnosis and procedure codes alone and is subject to misclassification Inability to link hospitalizations to individual patients limits longitudinal follow-up post-discharge |
Private Insurance Claims Data | United States Private insurance represents ~50% total market, often through employer | ICD-9CPT Pharmacy Laboratory |
| None | None | Relies on diagnosis and procedure codes Enrolled only while covered Often missing death data |
National Patient Registries | Denmark, Sweden, Ontario | Includes detailed information on clinical characteristics, laboratory data, imaging, procedures and outcomes |
| Thygesen et al. (2011) Lapointe-Shaw et al. (2018) | None | Country and health care system specific |
Organ Procurement and Transplant Network (OPTN) | United States Listed for liver transplantation | Manually entered detailed pre-, intra-, and post-transplant clinical information |
| None (manually input by transplant program) | None (manually input by transplant program) | Considerable selection bias given limited to transplant centers and listed patients Potential for misclassification due to inaccurate completion of questionnaire ELTR: No information on patient ethnicity or socioeconomic information |
European Liver Transplant Registry (ELTR) | Europe (155 centers from 28 countries) | Detailed information on liver transplant indications, transplant types and complications |
| None (manually input by transplant program) | None |
Study | Population | Definition of HE | Outcome(s) | |
---|---|---|---|---|
Incidence/Prevalence | Tapper | US Veterans with APRI>2.0 2005–2015 | ICD-9 572.2 or the use of lactulose and/or rifaximin | The cumulative probabilities of overt HE at 1, 3, and 5 years was 22.6%, 36.9%, and 43.6% |
Tapper | US Medicare 2008–2015 | Incidence rate: 11.6 per 100 person-years | ||
Nilsson | Sweden, 43% with ascites | Lactulose use | Cumulative incidence at 1 and 10 years, 6.4% and 26% | |
Mortality | Wong | Transplant waitlisted Americans 2003–2012 | Manually entered grading | HE is associated with mortality: Grade 1–2 1.1.3 (1.02–1.26) Grade 3–4: 1.65 (1.44–1.89) |
Scaglione | Privately insured Americans with cirrhosis and a readmission 2010–2014 | 572.2 | Adjusted mortality associated with HE 1.14 (1.04–1.24) | |
Tapper | US Medicare 2008–2015 Optum commercial claims 2008–2015 | ICD-9 572.2 or the use of lactulose and/or rifaximin | Median survival 0.95 and 2.5 years for those ≥65 or <65 years old; 1.1 and 3.9 years for those with or without ascites | |
Post-transplant mortality | Wong | Transplant waitlisted Americans 2003–2013 | Manually entered grading | HE is associated with mortality: Grade 3–4: 1.27 (1.17–1.39) |
Inpatient outcomes | Hirode | Hospitalized Americans 2010–2014 | ICD-9 572.2 | In-hospital mortality 12.3% from 13.4% Cost per admission 16,168 to 16,919 |
Stepanova | Hospitalized Americans 2005–2009 | ICD-9 572.2 | In-hospital mortality 15.6% to 14.3% Cost per admissions 16,512 to 17,812 | |
Tapper | US Medicare 2008–2015 Optum commercial claims 2008–2015 | ICD-9 572.2 or the use of lactulose and/or rifaximin | 11.8 (IQR 2.9–38.0) hospital days per person-year Combination lactulose and rifaxmin use associated with lower hospital days and 30 day readmission | |
Costs | Roggeri | Hospitalized Italians 2011 | ICD-9 572.2 | Annual HE costs: 15,295 USD |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Bloom, P.P.; Tapper, E.B. The Use of Administrative Data to Investigate the Population Burden of Hepatic Encephalopathy. J. Clin. Med. 2020, 9, 3620. https://doi.org/10.3390/jcm9113620
Bloom PP, Tapper EB. The Use of Administrative Data to Investigate the Population Burden of Hepatic Encephalopathy. Journal of Clinical Medicine. 2020; 9(11):3620. https://doi.org/10.3390/jcm9113620
Chicago/Turabian StyleBloom, Patricia P., and Elliot B. Tapper. 2020. "The Use of Administrative Data to Investigate the Population Burden of Hepatic Encephalopathy" Journal of Clinical Medicine 9, no. 11: 3620. https://doi.org/10.3390/jcm9113620
APA StyleBloom, P. P., & Tapper, E. B. (2020). The Use of Administrative Data to Investigate the Population Burden of Hepatic Encephalopathy. Journal of Clinical Medicine, 9(11), 3620. https://doi.org/10.3390/jcm9113620