Disease Management Interventions for

Patients with Cirrhosis

Primary Focus
Preventing Hospital Readmissions
National Liver Conference 2014
Robert Gish, MD
Current affiliations:
Robert G Gish MD
Robert G Gish Consultants LLC
Professor Consultant
Stanford University
RGish@stanfordmed.edu

Senior Medical Director
St Josephs Hospital and Medical Center
Phoenix, AZ

Medical Director
Hepatitis B Foundation
Doylestown, PA

Vice Chair Steering Committee
National Viral Hepatitis Roundtable
San Francisco, CA

Vice President
Fair Foundation
Palm Desert, CA


Work address:
6022 La Jolla Mesa Drive
La Jolla, CA 92037
Cell Phone: 858 229 9865
Fax Number: 858 8867093
Website: robertgish.com
Email: rgish@robertgish.com


Disclosures
Speakers list and advisory board for Salix Pharmaceuticals
>600,000 Cases of Cirrhosis in the
United States
1
Cirrhosis is a leading cause of death in the United States
More than 28,500 deaths annually
2

Most common causes of cirrhosis include alcohol use, hepatitis C,
and hepatitis B
2
Alcoholic liver disease: More than 2 million Americans (NIAAA)
3
Chronic hepatitis C infection: Almost 6 million Americans have
antibodies indicating infection or prior exposure and ~5 M infected
to day (NIDDK)
4
Chronic hepatitis B infection: 2.2 million Americans (NIAID)
5



NIAAA, National Institute on Alcohol Abuse and Alcoholism; NIAID, National Institute
of Allergy and Infectious Diseases; NIDDK, National Institute of Diabetes and Digestive and Kidney Diseases.
1. Dufour MC. In: Everhart, ed. Digestive Diseases in the United States: Epidemiology and Impact. 1994:613-646. NIH publication No. 94-1447. 2 . Xu,
et al. National Vital Statistics Report 2009;58:152. 3. Statistics by Country for Alcoholic Liver Disease.
http://www.cureresearch.com/a/alcoholic_liver_disease/stats-country.htm. Accessed January 4, 2012.
4. National Digestive Diseases Information Clearing House. Chronic Hepatitis C: Current Disease and Management.
http://digestive.niddk.nih.gov/ddiseases/pubs/chronichepc/index.htm. Accessed October 2, 2009.
5. American Liver Foundation. Hepatitis B. http://www.liverfoundation.org/education/info/hepatitisb/. Accessed October 2, 2009.
351,532
383,171
403,664
411,029
436,901
444,882
459,496
498,181
0
100,000
200,000
300,000
400,000
500,000
600,000
2002 2003 2004 2005 2006 2007 2008 2009
Hospital Discharges Due to Cirrhosis Is
Increasing
*ICD-9-CM diagnosis codes 571.2. 571.5, 571.6; all listed diagnoses.
HCUPnet, Healthcare Cost and Utilization Project. Agency for Healthcare Research and Quality, Rockville, MD.
http://hcupnet.ahrq.gov. Accessed January 4, 2012.
8% growth
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*

Year
90% Increase in HE Hospitalizations
Since 2004
HE, hepatic encephalopathy; ICD, International Classification of Diseases.
*All listed diagnoses at discharge included ICD codes 291.2 (alcoholic dementia, not elsewhere classified),
348.30 (encephalopathy, not otherwise specified), and 572.2 (hepatic coma).
HCUPnet, Healthcare Cost and Utilization Project. Agency for Healthcare Research and Quality, Rockville, MD.
http://hcupnet.ahrq.gov/HCUPnet.jsp. Accessed May 16, 2011.
182,843
196,521
215,767
239,425
323,564
345,887
0
50,000
100,000
150,000
200,000
250,000
300,000
350,000
2004 2005 2006 2007 2008 2009
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Year
Greater Than 50% Increase
in Cost Per HE Discharge
HE, hepatic encephalopathy; ICD, International Classification of Diseases.
*Data calculated using ICD-9-CM codes 291.2 (alcoholic dementia, not elsewhere classified),
348.30 (encephalopathy, not otherwise specified), and 572.2 (hepatic coma). Includes all listed discharge diagnoses.
HCUPnet, Healthcare Cost and Utilization Project. Agency for Healthcare Research and Quality, Rockville, MD.
http://hcupnet.ahrq.gov. Accessed July 6, 2011.
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,

22,511
25,415
26,541
29,065
32,764
35,242
$0
$5,000
$10,000
$15,000
$20,000
$25,000
$30,000
$35,000
$40,000
2004 2005 2006 2007 2008 2009
Year
Hospital Readmission in Patients with
Decompensated Cirrhosis
1
Readmission rates for patients with cirrhosis
14% readmitted within 1 week
37% readmitted within 1 month
Increased costs associated with readmissions
Week 1 associated cost of $28,898
Week 4 had an associated cost of $20,581
Predictors of readmission
MELD score, serum Na
+
, # of discharge medications
22% of readmissions were judged preventable
Most common HE secondary to lactulose
failure

Volk ML, et al. Am J Gastroenterol 2012;107:24752.
Hospital Readmissions
Hospitalizations account ~50% of health care expenses
13% of in-patients use >50% of hospital resources through
repeated admissions
Hospital readmissions cluster just after time of discharge
Most preventable readmissions have been reported to
occur within 30 days of discharge
Longstanding variations in readmission rates suggest the
system of transitional care to outpatient is flawed
Benbassat J, Taragin M. Arch Intern Med 2000;160:107481.
Hospital Readmissions:
Accountability Measure
June 2009: CMS began reporting 30-day hospital
readmission rates for pneumonia, AMI, and CHF
Patient Protection and Affordable Care Act
2013/2014: CMS will be reducing payments to hospitals based
on how they compare with the number of expected
readmissions for PNA, AMI, and HF
CMS will expand this approach to include other disease
states in the future, estimated that complications of
cirrhosis and readmissions will be under scrutiny

AMI, acute myocardial infarction; CMS, Centers for Medicare and Medicaid Services; HF, heart failure; PNA, pneumonia.
www.cms.org
Jencks SF, et al. N Engl J Med 2009;360:141828.
Characteristics of 34 Studies Measuring the Proportion
of Hospital Readmissions Deemed Avoidable
van Walraven C, et al. CMAJ 2011;183:E391402.
Proportion of Hospital Readmissions Deemed
Avoidable
Studies grouped by
value of study factors
with strongest association

Short-term re-
hospitalization at
nonteaching hospitals has
the highest rate of
readmissions deemed
avoidable

Error bars = 95% confidence intervals.
van Walraven C, et al. CMAJ 2011;183:E391402.
Readmissions and Quality of Care
Within the 957% readmissions judged to be preventable
Associated with substandard care
Poor resolution of main problem
Unstable therapy at discharge
Inadequate post-discharge care

1275% of all readmissions can be prevented by patient
education, pre-discharge assessment, and domiciliary
aftercare


Benbassat J, Taragin M. Arch Intern Med 2000;160:10741081.
Factors related to readmissions:
New acute diagnoses
New medications, dosages, and/or frequencies
Patients are often deconditioned
Patients and family lack of understanding of care plan
Health literacy
Transitions to out patient care bring opportunity for
mistakes
Communication with patient and between providers
is not always optimal
Rehospitalization After Large-Volume Paracentesis (LVP)
+/- Albumin Infusion: Meta-Analysis
*Albumin infusion vs. other treatments.
Bernardi M, et al. Hepatology 2012; 55:117281.
Meta-analysis of 17 randomized clinical trials comparing LVP plus albumin
vs. LVP plus alternative treatment or vs. LVP alone

*
Incidence and Predictors of 30-Day Readmission Among
Patients Hospitalized for Advanced Liver Disease
447 patients
2 large academic medical centers
30-day readmission rate 20%
Factors associated with 30-day
readmissions:
MELD scores
(OR 1.06, 95% CI 1.021.09, P=0.002)
Presence of diabetes mellitus
(OR 1.78, 95% CI 1.072.95, P=0.027)
Male gender
(OR 1.73, 95% CI 1.032.9)
90-day mortality rate was significantly
higher for patients readmitted to the
hospital within 30 days (26.8% vs. 9.8%
with OR 2.6, 95% CI 1.365.02, P=0.004)
Berman K, et al. Clin Gastroenterol Hepatol 2011;9:2549.
Incidence and Predictors of 30-Day Readmission Among
Patients Hospitalized for Advanced Liver Disease
Berman K, et al. Clin Gastroenterol Hepatol 2011;9:2549.
Hospital Readmissions Related to Cirrhosis
Advanced liver disease a leading cause of death in the USA
>150,000 hospitalizations/year
>40,000 deaths/year
Costs ~$4 billion dollars/year
~2037% of patients are readmitted to hospital within
30 days of discharge
~20% of these readmissions may be preventable
Each readmission within 30 days costs $20,000$28,000
2/3 of all patients covered by Medicare or Medicaid
Volk ML. Am J Gastroenterol 2012;107:24752.
Hospital Readmissions Among Patients
with Decompensated Cirrhosis
Retrospective study, July 2006 July 2009,
University of Michigan
402 patients readmitted for:
Ascites
SBP
Renal failure
Hepatic encephalopathy
Variceal bleeding
Aim: Identify frequency, costs, predictors, and preventable
causes of hospital readmissions

SBP, spontaneous bacterial peritonitis.
Volk ML, et al. Am J Gastroenterol 2012;107:24752.
30-Day Readmissions and Quality of Care, Really?
Highly debatable
Metric is problematic: many factors outside control of hospital
Extrinsic factors (modifiable vs. non-modifiable)
Geography, patient population, social support, mental illness,
resources in the community, progression of disease, health literacy, etc.
Intrinsic factors
Health system operations, infrastructure and priorities
Medication reconciliation and patient education
Communication about plan of care
Follow-up appointments set and reminders submitted
Some experts suggest 3- and 7-day readmissions are more within hospital
control
[Comment on limitations of Volk ML, et al. Am J Gastroenterol 2012;107:24752.]
Results
1 non-elective readmission within
1 week: 14%
1 month: 37%
Mean costs for readmissions
Within 1 week: $28,898
Weeks 14: $20,581
Predictors of readmissions:
MELD
Serum sodium
Number of medications at discharge
Among 165 readmissions within 30 days
22% were possibly preventable
Most common preventable reasons:
Hepatic encephalopathy
Fluid imbalance (hyper or hypovolemia)
Volk ML, et al. Am J Gastroenterology 2012;107:24752.
Multivariable analysis of predictors
of time to first readmission
Results
Readmissions categorized as possibly preventable if there
was evidence a modification in the health-delivery system
may have helped prevent the admission
Improved patient education
Adherence to medications
Closer follow-up

Concordance between 2 reviewers was 83%
Volk ML, et al. Am J Gastroenterology 2012;107:24752.
Hospital Readmissions Related to Cirrhosis
Advanced liver disease a leading cause of death in the USA
>150,000 hospitalizations/year
>40,000 deaths/year
Costs ~$4 billion dollars/year
~2037% of patients are readmitted to hospital within
30 days of discharge
~20% of these readmissions may be preventable
Each readmission within 30 days costs $20,000$28,000
2/3 of all patients covered by Medicare or
Medicaid
Volk ML. Am J Gastroenterol 2012;107:24752.
Probiotic Preparation in the Secondary
Prophylaxis of Hepatic Encephalopathy
Randomized, double-blind, placebo-controlled trial
103 patients with liver cirrhosis who have recovered from an episode of HE
during the previous 1 month received a probiotic preparation (900 billion
bacteria daily, n = 51) or placebo (n = 52) for 6 months
Treatment with probiotic significantly reduced the risk of overall and HE-related
hospitalizations
Dhiman RK ,et al. Abstract 124. Oral presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Probiotic
(n = 51)
Placebo
(n = 52)
Hazard Ratio;
(95% CI); P value
Hospitalizations
overall (%)
19.6% 42.3% 0.45
(0.210.95)
0.036
Hospitalizations
involving HE (%)
15.7% 36.5% 0.42
(0.180.95)
0.037
Readmission Rates and Maintenance of
Overt Hepatic Encephalopathy (OHE)
Retrospective evaluation of economic differences (primarily
hospitalizations) associated with the various medical
therapies for OHE

Choice of maintenance therapy following an OHE episode
has a significant effect on overall costs associated with
overt hepatic encephalopathy
Rifaximin is nearly 50% more cost efficient than lactulose
monotherapy or lactulose/ rifaximin combination therapy
Rifaximin therapy results in less frequent hospitalizations and
longer intervals between readmissions

Neff GW, et al. Abstract P1349. ACG Annual Scientific Meeting and Postgraduate Course, Las Vegas, NV, October 23, 2012.
Lactulose Noncompliance is Leading
Factor for HE Recurrence
GI, gastrointestinal; HE, hepatic encephalopathy; TIPS, transjugular intrahepatic portosystemic shunt.
*HE recurrence defined as hospitalization for HE recurrence or changes in mental status consistent with HE in
outpatients. Noncompliance inferred with evidence (as documented in patient charts) of discontinuation of
Lactulose as prescribed (determined by questioning patient or family members); lack of Lactulose refill according
to pharmacy records; and <2 bowel movements/day, for at least 1 month. Lactulose-induced dehydration defined
as >4 bowel movements/day with dehydration and azotemia (new rise in serum creatinine >1.5 mg/dL).
Bajaj JS, et al. Aliment Pharmacol Ther 2010;31:10127.
38
8
10
19
15
7
4
0
10
20
30
40
50
Lactulose
noncompliance

Lactulose-
induced
dehydration

Spontaneous

Sepsis GI bleed TIPS
placement
New-onset
hyponatremia
n = 103
P
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Treatment Effect of Rifaximin 550:
Reduction in HE-related Hospitalizations
1,2,*
HE, hepatic encephalopathy; HR, hazard ratio.
*HE-related hospitalization defined as hospitalization directly caused by HE or a hospitalization during which an HE
event occurred. Lactulose was used concomitantly by 91% of patients in both arms.
1. Bass NM, et al. N Engl J Med 2010;362:107181. 2. XIFAXAN [package insert]. Salix Pharmaceuticals, Inc; 2010.
rifaximin
Need for Interventions
Expanding evidence shows serious deficits in quality exist
for patients undergoing transitions across sites of care
Patients are often unprepared for self-management role
Receive conflicting information about management of their
chronic illness
Often unable to contact care provider


Care Transition Interventions Study
Randomized, controlled trial
Conducted in collaboration with large not-for-profit
capitated delivery system with more than 60,000 patients
65 years and older in Colorado
Contracts with a single hospital, 8 SNFs, and 1 home health
care agency
Before initiation, hospital 30-day readmission rate was ~15%
750 Patients were randomized in study, 712 included in
analysis (stroke, CHF, CAD, arrhythmia, COPD, DM, hip
fracture, dehydration, PNA)

CAD, coronary artery disease; CHF, coronary heart failure; COPD, chronic obstructive pulmonary disorder; DM,
diabetes mellitus; PNA, peneumonia; SNF, skille nursing facility.
Coleman EA, et al. Arch Intern Med 2006;166:18228.
Care Transition Interventions
Coleman EA, et al. Arch Intern Med 2006;166:18228.
Characteristics of Study Sample
Care Transition Interventions

PHR, personal health record.
Coleman EA, et al. Arch Intern Med 2006;166:18228.
Care Transition Interventions
Coleman EA, et al. Arch Intern Med 2006;166:18228.
Results
Improved medication management
Improved self-management knowledge and skills
Continuity of care fosters a sense of caring, safety, and
predictability between inpatient and outpatient settings

Coleman EA, et al. Arch Intern Med 2006;166:18228.
UHC 2011 Database:
% Readmissions by Hospital in California
(MS-DRG Cirrhosis and Alcoholic Hepatitis)
0
5
10
15
20
25
30-Day
14-Day
7-Day
UHC 2011 Database:
% Readmissions by Hospital in California
(MS-DRG Major GI Disorders and Peritoneal Infx)
0
2
4
6
8
10
12
14
16
18
30-Day
14-Day
7-Day
Studies are needed!
No studies have evaluated the impact of interventions in
reducing preventable hospital readmissions in patients with
cirrhosis

Cirrhosis patients represent exactly the type of population
with high morbidity, mortality, and resource utilization that
has been the target of (CMS) efforts in the past

Volk ML, et al. Am J Gastroenterology 2012;107:24752.
An Automated Model Using
Electronic Medical Record Data
Identifies Patients with Cirrhosis
at High Risk for Readmission
Amit G Singal, Robert S Rahimi, Christopher Clark,
Ying Ma, Jennifer A Cuthbert, Don C Rockey,
Ruben Amarasingham

Clin Gastroenterol Hepatol 2013;11:133541.

Background and Methods
Background: Early identification of patients with cirrhosis who are at high risk of
hospital readmission could allow targeted preventative interventions
Aim: to construct an electronic model to stratify 30-day readmission risk
Design: Retrospective analysis of present-on-admission data from electronic
medical records (EMRs) for patients with cirrhosis admitted to Parkland
Memorial Hospital between Jan 2008 and Dec 2009
Outcome variables
Primary outcome: any-cause rehospitalization, excluding elective admissions, to
hospitals in the DallasFort Worth area within 30 days of the index hospitalization
Secondary outcome: all-cause mortality within 90 days of discharge
Predictor variables
Clinical data (including demographics, medical history, laboratory parameters)
Markers of social, behavioural and utilization activity from electronic data sources
Model: multiple logistic regression
Singal AG, et al. Clin Gastroenterol Hepatol 2013;11:133541.
Results: Patients
836 patients, 1291 unique admission encounters
Mean age 52.5 years (range 19/90 years)
Male 67.6%, single 67.3%
African American 22.9%, Non-Hispanic Caucasian 32.5%, Hispanic Caucasian
40.3%
40.6% Medicaid, 16.0% private health insurance
Average length of hospitalization 5.9 days

Rehospitalization within 30 days for 27% of patients


Singal AG, et al. Clin Gastroenterol Hepatol 2013;11:133541.
Results: Multiple Logistic Regression
of Predictors for 30-Day Readmission

a
All variables were collected within 48 hours of admission from the EMR.
b
ORs greater than 1.0 are associated with a higher risk of
30-day readmission, and ORs less than 1.0 are associated with a lower risk of readmission.
Singal AG, et al. Clin Gastroenterol Hepatol 2013;11:133541.
Variable
a
30-Day
Readmission Risk OR (95% CI)
b
p Value
Number of address changes in the year
before index hospitalization (continuous)


1.13 (1.051.21) 0.001
0 address changes
1 address change
2 address changes
24%
28%
30%
Number of admissions in the year before
index hospitalization (continuous)
1.14 (1.051.24) 0.002
0 admissions
1 admission
2 admissions
20%
25%
35%
Medicaid insurance 33% 1.53 (1.102.13) 0.012
Results: Multiple Logistic Regression
of Predictors for 30-Day Readmission
Variable
a
30-Day
Readmission Risk OR (95% CI)
b
p Value
Platelet count 0.50 (0.350.72) <0.001
<77,000/mL
77,000112,000/mL
>112,000/mL
28%
18%
30%
ALT level 2.56 (1.096.00) 0.031
9 U/L
>9 U/L
48%
26%
Hematocrit 1.63 (1.172.27) 0.004
30%
>30%
37%
22%
Sodium level 1.78 (1.142.80) 0.012
<130 mEq/L
>130 mEq/L
40%
25%
MELD score (continuous) 1.04 (1.011.06) 0.004

a
All variables were collected within 48 hours of admission from the EMR.
b
ORs greater than 1.0 are associated with a higher risk of
30-day readmission, and ORs less than 1.0 are associated with a lower risk of readmission.
Singal AG, et al. Clin Gastroenterol Hepatol 2013;11:133541.
Results: Risk Stratification Model
The electronic model was capable of stratifying patients across a wide range of
risk with high concordance between derivation and validation cohorts

Singal AG, et al. Clin Gastroenterol Hepatol 2013;11:133541.
Time to readmission stratied
by readmission model risk quintile
Patients in the lowest-risk
category had a signicantly
longer time to readmission than
those in the highest-risk group
(P .001)
Conclusion
Early rehospitalization among patients with cirrhosis was
common (27% within 1 month of discharge)
Predictors of readmission in multiple logistic regression
included clinical and socioeconomic variables
The model for stratifying risk using electronically available
data identified patients at low risk (<20%) and high risk (45%)
for readmission within 30 days
Singal AG, et al. Clin Gastroenterol Hepatol 2013;11:133541.
Factors related to readmissions:
New acute diagnoses
New medications, dosages, and/or frequencies
Patients are often deconditioned
Patients and family lack of understanding of care plan
Health literacy
Transitions to out patient care bring opportunity for
mistakes
Communication with patient and between providers
is not always optimal
Conclusion
Readmission to the hospital for complications of liver disease are highly
preventable

Team discharge planning and confirmation of correct medications and
delivery of medications to patients prior to discharge are essential

Addressing all aspects of the complex patients problem list and most
importantly, the reason for admission to prevent both early and mid-
term times of readmission

Use EHR and EMR to trigger care management decisions

Use Pharmacy team to assist in DC planning and transitions
Factor that need to be addressed
Hyponatremia
Circulatory dysfunction
Adrenal insufficiency
Infections
Hepatic encephalopathy
Patients need to have HE medication in hand at time of DC
GI bleeding