Evaluation of the impact of rehospitalization in the management of hepatic encephalopathy

Figures & data

Figure 1 PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram summary of search outcomes. Data from systematic review of PubMed database performed initially in July 2014 and again in February 2015.

Note: *Secondary search strings.
Abbreviation: HE, hepatic encephalopathy.

Table 1 Relevant published studies of the impact of rehospitalization costs and clinical outcomes in hepatic encephalopathy (HE)

Study	Study design	Setting	Population	Key findings
Journal articles
Arguedas et al^Citation16	Cross-sectional study	US university medical center	160 consecutive adults with cirrhosis presenting for initial liver transplantation	• Patients with cirrhosis had lower SF-36^® scores than the general US population • Advanced cirrhosis was associated with significantly lower PCS scores and RP (P=0.01), BP (P=0.037), GH (P=0.028), and SF (P=0.034) domains
Bajaj et al^Citation17	Cross-sectional study	Outpatient clinics in two US university medical centers	Part A: 226 patients with (n=54) or without (n=172) history of overt HE Part B: 50 patients with cirrhosis who had experienced ≥1 overt HE episode	• Patients with minimal HE performed significantly worse on cognitive testing than normal cirrhotic patients • Psychometric scores highly correlated with number of HE episodes and hospital admissions for overt HE
Dhiman et al^Citation27	Randomized, double-blind, placebo-controlled study	Tertiary-level health care center in Chandigarh, India	130 patients with cirrhosis who had recovered from a previous episode of HE in the prior month	• Probiotic use significantly reduced hospitalizations for breakthrough episodes of HE, with concomitant improvements in HRQOL • Probiotic use was associated with SF-36 improvement in physical function, role physical, and physical component summary domains
Fichet et al^Citation6	Retrospective chart review	Medical ICU in French university hospital	71 patients with severe HE	• Overall mortality rate at 1 year of 54% (36/66), with a 39.5% in-hospital mortality rate
Huang et al^Citation18	Decision-analysis model	Analysis conducted from perspective of US third-party payer	NA	• Cost of hospitalization for advanced encephalopathy of US$23,192 • Lactulose monotherapy and rifaximin salvage were found to be potentially cost-effective
Montagnese et al^Citation19	Cross-sectional study	Specialist clinic at an Italian university medical center	35 consecutive outpatients with cirrhosis and history of overt HE episodes and chronic treatment referred to specialist clinic for formal evaluation; 31 caregivers	• HE adversely affects patient QOL and presents a burden on caregivers • HE awareness is poor in patients with cirrhosis and their caregivers, attributed to a deficit in information being distributed
Neff et al^Citation9	HCUP data analysis	HCUP database (2004–2010)	Patients with any ICD-9-CM discharge diagnosis indicative of HE	• Cost per HE discharge increased by >50% between 2004 and 2010 • Cause of the cost increase may be attributed to new therapies that are more beneficial
Onyekwere et al^Citation20	Prospective, observational study	Medical wards of the Lagos State University Teaching Hospital, Ikeja	21 patients with HE and a background of liver disease	• In-hospital mortality rate of 48% (10/21 patients) • Those at risk for HE should be routinely screened to detect latent encephalopathy
Poordad^Citation12	Nationwide Inpatient Sample data analysis	Nationwide Inpatient Sample (2002)	40,012 patients with primary diagnosis of HE	• Cumulative hospital charges for a primary diagnosis of HE increased substantially from 1993 to 2003, totaling approximately US$7 billion • Future economic evaluations should identify therapies that positively impact clinical and economic outcomes
Stepanova et al^Citation11	Nationwide Inpatient Sample data analysis	Nationwide Inpatient Sample (2005–2009)	33.3 million hospitalizations, including 111,090 hospitalizations with HE	• Total charges for HE-related hospitalizations increased from US$4.7 billion in 2005 to US$7.3 billion in 2009, a 55% increase • The inpatient mortality rate for patients with HE decreased from 15.6% in 2005 to 14.4% in 2009 (P=NS) • Inpatient hospitalizations for advanced liver disease and HE complications are increasing, with consistent increases in socioeconomic and financial burden
Udayakumar et al^Citation21	Prospective, observational study	Medical ICU at Indian university hospital	50 consecutive patients admitted with HE associated with acute or chronic liver disease	• The in-hospital mortality rate is high for patients with HE: 33% for chronic cases and 64% for acute cases • High bilirubin levels were prognostic of poor outcomes in patients with chronic liver disease
Volk et al^Citation22	Retrospective chart review	US university health system medical center	402 patients with decompensated cirrhosis; 276 patients with ≥1 non-elective readmission	• There was a median rate of three hospitalizations per person-years for patients with decompensated cirrhosis • Patients who were more often readmitted to the hospital had higher risk of subsequent mortality (hazard ratio, 1.08; P<0.001) • The mean cost of readmission within 4 weeks of discharge was US$20,581
Meeting abstracts
Congly et al^Citation23	Cost–utility analysis using Markov model based on clinical trial data	NA	Patients with history of HE	• The model predicts 5-year survival rates of 32%, 30%, and 24.5% for patients treated with rifaximin (upfront), rifaximin (salvage), and lactulose, respectively • The largest drivers of cost were hospitalization and rifaximin use • Adding rifaximin to treatment regimens may be cost-effective
Kim et al^Citation8	Nationwide Inpatient Sample data analysis	Nationwide Inpatient Sample (2006)	65,072 discharge records associated with hospitalization for complications of cirrhosis	• 41% of hospitalizations among patients with cirrhosis were attributed to encephalopathy • Encephalopathy was associated with a twofold higher probability of inpatient mortality (P<0.01)
Masadeh et al^Citation24	1-year retrospective chart review	US university tertiary hospital	139 patients admitted with a complication related to liver cirrhosis (36% with HE)	• 31% of patients overall were readmitted within 30 days; 47% of these cases were attributed to HE • This model can be used to identify patients at higher risk for readmission, which may afford an opportunity for quality improvement
Masadeh et al^Citation25	1-year retrospective chart review	US university tertiary hospital	139 patients admitted with a complication related to liver cirrhosis	• 36% of hospital admissions for liver cirrhosis were attributed to HE • HE was the most common cause of readmission within 30 days, followed by fluid overload
Neff et al^Citation14	Premier Research Database analysis	Premier Research Database (information from >500 US hospitals)	8,766 patients discharged from June 2010 to December 2011 with primary diagnosis of HE	• In-hospital mortality rate was 7.3% • Mean cost per hospitalization was US$10,629 • Incidence rates for all-cause readmissions were 27.4% (30 days) and 56.4% (1 year); rates for HE-related readmissions were 17.6% (30 days) and 39.5% (1 year)
Neffet al^Citation26	Retrospective chart review	US community hospital	145 patients with ≥1 hospitalization for overt HE within a 6-month period	• Predictors of hospital readmission included lack of compliance, lack of provider follow-up, lack of social support, type of insurance (Medicaid, insurance, or no insurance), and lack of employment • New methods are needed to identify patients at risk for readmission and to deliver value-based medicine

Abbreviations: BP, bodily pain; GH, general health perception; HCUP, Healthcare Cost and Utilization Project; HE, hepatic encephalopathy; HRQOL, health-related quality of life; ICD-9-CM, International Classification of Diseases, Ninth Revision, Clinical Modification; ICU, intensive care unit; NA, not applicable; NS, not significant; PCS, physical component summary; QOL, quality of life; RP, role limitation-physical; SF, social functioning; SF-36, Short Form (36) Health Survey.

Table 2 Correlation between psychometric tests and the number of hospitalizations for or episodes of overt hepatic encephalopathy (HE) (N=50)

Psychometric testa	Cognitive function(s) evaluated	Number of hospitalizations for overt HE		Number of episodes of overt HE
		r	P-value	r	P-value
Digit symbol test (raw score)	Psychomotor speed, attention, and visual memory	−0.39	0.02	−0.46	0.009
ICT lures (n)	Response inhibition, attention, and working memory	0.50	0.002	0.59	0.001
ICT targets (% correct)	Reaction time	−0.43	0.009	−0.44	0.015
Number connection-A (speed)	Psychomotor speed	0.26	0.144	0.22	0.238
Number connection-B (speed)	Psychomotor speed, set shifting (ie, mental flexibility in switching between tasks), and divided attention	0.35	0.047	0.35	0.05
Block design test (raw score)	Visuomotor coordination, visuospatial reasoning, praxis, and psychomotor speed	−0.11	0.631	−0.20	0.378

Notes: Bold values indicate statistical significance.

a A high score on number connection-A, connection-B, and ICT lures, and a low score on digit symbol, block design, and ICT target number indicate poor psychometric performance.

Adapted with permission from Gastroenterology, vol 138, no 7, Bajaj JS, Schubert CM, Heuman DM, et al. Persistence of cognitive impairment after resolution of overt hepatic encephalopathy, pages 2332–2340, Copyright 2010 with permission from Elsevier.¹⁷

Abbreviation: ICT, inhibitory control test.

Figure 2 Acute and long-term management of overt hepatic encephalopathy (HE).

Notes: ^aRoutine prophylaxis (lactulose or rifaximin) is not recommended for prevention of overt HE in patients with a transjugular intrahepatic portosystemic shunt. Data from Vilstrup H, Amodio P, Bajaj J, et al.²

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