Slide 1

Disease Management Interventions for Patients with CirrhosisPrimary FocusPreventing Hospital ReadmissionsNational Liver Conference 2014Robert Gish, MDCurrent affiliations:Robert G Gish MDRobert G Gish Consultants LLCProfessor ConsultantStanford UniversityRGish@stanfordmed.edu

Senior Medical DirectorSt Josephs Hospital and Medical CenterPhoenix, AZ

Medical DirectorHepatitis B FoundationDoylestown, PA

Vice Chair Steering CommitteeNational Viral Hepatitis RoundtableSan Francisco, CA

Vice PresidentFair FoundationPalm Desert, CA

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

DisclosuresSpeakers list and advisory board for Salix Pharmaceuticals>600,000 Cases of Cirrhosis in the United States1Cirrhosis is a leading cause of death in the United StatesMore than 28,500 deaths annually2 Most common causes of cirrhosis include alcohol use, hepatitis C, and hepatitis B2Alcoholic liver disease: More than 2 million Americans (NIAAA)3Chronic hepatitis C infection: Almost 6 million Americans have antibodies indicating infection or prior exposure and ~5 M infected to day (NIDDK)4Chronic 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. 44Hospital 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% growthNumber of discharges forpatients with cirrhosis*Year90% Increase in HE Hospitalizations Since 2004HE, 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.

Total numberof dischargesYear Since 2004, hospitalizations of patients with HE have been increasingBased on hospital discharge data from the Healthcare Cost and Utilization Project and using ICD-9-CM codes 291.2, 348.30, and 572.2291.2 = alcoholic dementia, not elsewhere classified348.30 = encephalopathy, not otherwise specified572.2 = hepatic coma In 2009, there were more than 345,000 hospitalizations for patients with HE

Reference: HCUPnet, Healthcare Cost and Utilization Project. National statisticsall-listed. Agency for Healthcare Research and Quality, Rockville, MD. http://hcupnet.ahrq.gov/HCUPnet.jsp. Accessed May 16, 2011.

6Greater Than 50% Increase in Cost Per HE DischargeHE, 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.Cost per HE patient discharge*,

Year7Hospital Readmission in Patients with Decompensated Cirrhosis1Readmission rates for patients with cirrhosis14% readmitted within 1 week37% readmitted within 1 monthIncreased costs associated with readmissionsWeek 1 associated cost of $28,898Week 4 had an associated cost of $20,581Predictors of readmissionMELD score, serum Na+, # of discharge medications22% of readmissions were judged preventableMost common HE secondary to lactulose failure

Volk ML, et al. Am J Gastroenterol 2012;107:24752.8Hospital ReadmissionsHospitalizations account ~50% of health care expenses13% of in-patients use >50% of hospital resources through repeated admissionsHospital readmissions cluster just after time of dischargeMost preventable readmissions have been reported to occur within 30 days of dischargeLongstanding variations in readmission rates suggest the system of transitional care to outpatient is flawedBenbassat J, Taragin M. Arch Intern Med 2000;160:107481.Hospital Readmissions:Accountability MeasureJune 2009: CMS began reporting 30-day hospital readmission rates for pneumonia, AMI, and CHFPatient Protection and Affordable Care Act2013/2014: CMS will be reducing payments to hospitals based on how they compare with the number of expected readmissions for PNA, AMI, and HFCMS 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 Avoidablevan Walraven C, et al. CMAJ 2011;183:E391402.12

Proportion of Hospital Readmissions Deemed AvoidableStudies 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:E391402.13Readmissions and Quality of CareWithin the 957% readmissions judged to be preventableAssociated with substandard carePoor resolution of main problemUnstable therapy at dischargeInadequate 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 diagnosesNew medications, dosages, and/or frequenciesPatients are often deconditionedPatients and family lack of understanding of care planHealth literacyTransitions to out patient care bring opportunity for mistakesCommunication with patient and between providers is not always optimalRehospitalization 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 Disease447 patients2 large academic medical centers30-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 CirrhosisAdvanced liver disease a leading cause of death in the USA>150,000 hospitalizations/year>40,000 deaths/yearCosts ~$4 billion dollars/year~2037% of patients are readmitted to hospital within 30 days of discharge~20% of these readmissions may be preventableEach readmission within 30 days costs $20,000$28,0002/3 of all patients covered by Medicare or MedicaidVolk ML. Am J Gastroenterol 2012;107:24752.Hospital Readmissions Among Patients with Decompensated CirrhosisRetrospective study, July 2006 July 2009, University of Michigan402 patients readmitted for:AscitesSBPRenal failureHepatic encephalopathyVariceal bleedingAim: 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 debatableMetric is problematic: many factors outside control of hospitalExtrinsic factors (modifiable vs. non-modifiable)Geography, patient population, social support, mental illness, resources in the community, progression of disease, health literacy, etc.Intrinsic factorsHealth system operations, infrastructure and prioritiesMedication reconciliation and patient educationCommunication about plan of careFollow-up appointments set and reminders submittedSome 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.]Results1 non-elective readmission within1 week: 14% 1 month: 37%Mean costs for readmissionsWithin 1 week: $28,898Weeks 14: $20,581Predictors of readmissions:MELDSerum sodiumNumber of medications at dischargeAmong 165 readmissions within 30 days22% were possibly preventableMost 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 readmissionResultsReadmissions categorized as possibly preventable if there was evidence a modification in the health-delivery system may have helped prevent the admissionImproved patient educationAdherence to medicationsCloser follow-up

Concordance between 2 reviewers was 83%Volk ML, et al. Am J Gastroenterology 2012;107:24752.Hospital Readmissions Related to CirrhosisAdvanced liver disease a leading cause of death in the USA>150,000 hospitalizations/year>40,000 deaths/yearCosts ~$4 billion dollars/year~2037% of patients are readmitted to hospital within 30 days of discharge~20% of these readmissions may be preventableEach readmission within 30 days costs $20,000$28,0002/3 of all patients covered by Medicare or MedicaidVolk ML. Am J Gastroenterol 2012;107:24752.Probiotic Preparation in the Secondary Prophylaxis of Hepatic EncephalopathyRandomized, double-blind, placebo-controlled trial103 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 monthsTreatment with probiotic significantly reduced the risk of overall and HE-related hospitalizationsDhiman 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 valueHospitalizations overall (%)19.6%42.3%0.45(0.210.95)0.036Hospitalizationsinvolving HE (%)15.7%36.5%0.42(0.180.95)0.037Readmission 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 encephalopathyRifaximin is nearly 50% more cost efficient than lactulose monotherapy or lactulose/ rifaximin combination therapyRifaximin 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 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.

LactulosenoncomplianceLactulose-induceddehydrationSpontaneousSepsisGI bleedTIPSplacementNew-onsethyponatremian = 103Patients with factor, %Treatment Effect of Rifaximin 550: Reduction in HE-related Hospitalizations1,2,*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.

rifaximin28Over the 6 months of the study, Xifaxan 550 mg twice daily reduced the percentage of patients with HE-related hospitalization1That is, hospitalization directly caused by HE or a hospitalization during which an HE event occurredAt 6 months, 14% of patients in the Xifaxan 550 mg group had an HE-related hospitalization compared with 23% of patients in the placebo group1These results reflect a relative reduction in the risk of HE-related hospitalization by 50% compared with placebo over the 6 month period1,2The hazard ratio was 0.50 (95% CI, 0.29 to 0.87; P=0.0129)

References: 1. Bass NM, Mullen KD, Sanyal A, et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010;362(12):1071-1081. 2. XIFAXAN [package insert]. Morrisville, NC: Salix Pharmaceuticals, Inc; 2010.

Need for InterventionsExpanding evidence shows serious deficits in quality exist for patients undergoing transitions across sites of carePatients are often unprepared for self-management roleReceive conflicting information about management of their chronic illnessOften unable to contact care provider

Care Transition Interventions StudyRandomized, controlled trialConducted in collaboration with large not-for-profit capitated delivery system with more than 60,000 patients 65 years and older in ColoradoContracts with a single hospital, 8 SNFs, and 1 home health care agencyBefore 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 InterventionsColeman 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 InterventionsColeman EA, et al. Arch Intern Med 2006;166:18228.

ResultsImproved medication management Improved self-management knowledge and skillsContinuity 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)UHC 2011 Database:% Readmissions by Hospital in California (MS-DRG Major GI Disorders and Peritoneal Infx)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 UsingElectronic Medical Record Data Identifies Patients with Cirrhosis at High Risk for ReadmissionAmit 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 MethodsBackground: Early identification of patients with cirrhosis who are at high risk of hospital readmission could allow targeted preventative interventionsAim: 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 2009Outcome variablesPrimary outcome: any-cause rehospitalization, excluding elective admissions, to hospitals in the DallasFort Worth area within 30 days of the index hospitalizationSecondary outcome: all-cause mortality within 90 days of dischargePredictor variablesClinical data (including demographics, medical history, laboratory parameters)Markers of social, behavioural and utilization activity from electronic data sourcesModel: multiple logistic regressionSingal AG, et al. Clin Gastroenterol Hepatol 2013;11:133541.Results: Patients836 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 insuranceAverage 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 ReadmissionaAll variables were collected within 48 hours of admission from the EMR. bORs 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.Variablea30-Day Readmission RiskOR (95% CI)bp ValueNumber 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 changes24%28%30%Number of admissions in the year before index hospitalization (continuous)1.14 (1.051.24)0.002 0 admissions 1 admission 2 admissions20%25%35%Medicaid insurance33%1.53 (1.102.13)0.012Results: Multiple Logistic Regression of Predictors for 30-Day ReadmissionVariablea30-Day Readmission RiskOR (95% CI)bp ValuePlatelet count0.50 (0.350.72)9 U/L48%26%Hematocrit1.63 (1.172.27)0.004 30% >30%37%22%Sodium level1.78 (1.142.80)0.012 130 mEq/L40%25%MELD score (continuous)1.04 (1.011.06)0.004aAll variables were collected within 48 hours of admission from the EMR. bORs 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 ModelThe 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 quintilePatients in the lowest-risk category had a signicantly longer time to readmission than those in the highest-risk group (P .001)ConclusionEarly 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 (