Outcomes, Mortality, and Cost Burden of Acute Kidney Injury and Hepatorenal Syndrome in Patients with Cirrhosis.

BACKGROUND AND AIMS: Cirrhosis is associated with an increased risk of acute kidney injury (AKI) and hepatorenal syndrome (HRS). Healthcare utilization and cost burden of AKI and HRS in cirrhosis is unknown. We aimed to analyze the health care use and cost burden associated with AKI and HRS in patients with cirrhosis in the United States by using real-world claims data. METHODS: We conducted a case-control study using the Truven Health MarketScan Commercial Claims databases from 2007-2017. A total of 34,398 patients with cirrhosis with or without AKI and 4,364 patients with cirrhosis with or without HRS were identified using International Classification of Diseases, Ninth or Tenth Revision, codes and matched 1:1 by sociodemographic characteristics and comorbidities using propensity scores. Total and service-specific were quantified for the 12-months following versus the 12-months before the first date of AKI or HRS diagnosis and over 12-months following a randomly selected date for cirrhosis controls to capture entire disease burdens. RESULTS: The AKI and HRS group had a higher number of comorbidities and were associated with higher rates of readmission and mortality. The AKI and HRS groups had a significantly higher prevalence of ascites, spontaneous bacterial peritonitis (SBP), encephalopathy, gastrointestinal bleeding, septic shock, pulmonary edema, and respiratory failure. Compared to patients with cirrhosis only, AKI was associated with higher number of claims per person (AKI vs. cirrhosis only, 60.30 vs. 47.09; p<0.0001) and total annual median health care costs (AKI vs. cirrhosis only, $46,150 vs. $26,340; p<0.0001). Compared to patients with cirrhosis only, the HRS cohort was associated with a higher number of claims per person (HRS vs. cirrhosis only, 44.96 vs. 43.50; p<0.0009) and total annual median health care costs (HRS vs. cirrhosis only, $34,912 vs. $23,354; p<0.0001). Inpatient costs were higher than the control cohort for AKI (AKI vs. cirrhosis only, $72,720 vs. $29,111; p<0.0001) and HRS (HRS vs. cirrhosis only, $ 98,246 vs. $27,503; p<0.0001). Compared to the control cohort, AKI and HRS had a higher rate of inpatient admission, mean number of inpatient admissions, and mean total length of stay. CONCLUSIONS: AKI and HRS are associated with higher health care utilization and cost burden compared to cirrhosis alone, highlighting the importance for improved screening and treatment modalities.

Cost-effectiveness and potential value of pharmaceutical treatment of nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with substantial morbidity, mortality, and economic burden. With currently no approved treatment, an effective pharmaceutical intervention for this disease must be both clinically- and cost-effective. METHODS: A Markov model was constructed to estimate the clinical outcomes, costs, and quality of life impact of a hypothetical pharmaceutical intervention. Lifetime clinical outcomes, life-years, quality-adjusted life-years (QALYs), costs (2020 $US), incremental cost-effectiveness ratios (ICERs), and economically justifiable prices (EJPs) were quantified. Only patients with fibrosis stage F2-F4 were assumed eligible to initiate pharmaceutical treatment. RESULTS: Over a mean life expectancy of approximately 21 years in the simulated cohort, drug treatment reduced liver-related mortality by 6.0% (2.7% absolute reduction). Assuming an annual drug cost of $36,000, total discounted medical costs were $574,238 and $120,312 for drug and usual care, respectively, with discounted QALYs estimated to be 9.452 and 9.272 for the two comparators. This yielded an ICER of $2,517,676/QALY gained. The EJP of the drug at an ICER threshold of $150,000/QALY gained was $2,633, a 93% reduction from a base case. Sensitivity analyses suggest that, without a substantial decrease in the drug price, ICERs would exceed $500,000/QALY gained even with the most favorable efficacy assumptions. CONCLUSIONS: For a pharmaceutical intervention to be considered cost-effective in the NAFLD fibrosis population, the substantial clinical benefit will need to be coupled with a modest annual price. Annual drug costs exceeding $12,000 likely will not provide reasonable value, even with favorable efficacy. More work is needed to estimate the cost-effectiveness of lifestyle modifications.

Wilson's Disease: An Analysis of Health Care Use and Cost Burden of Commercially Insured Adults in the United States.

The economic and health care use burdens of Wilson's disease (WD) are unknown. In this study, we aimed to quantify this health care resource use and economic burden. We performed a retrospective case-control analysis of individuals in the Truven Health MarketScan Commercial Claims database (2007-2017). Using propensity scores, 424 WD cases were matched 1:1 to chronic liver disease (CLD) controls without WD. Total and service-specific parameters, expressed in monthly averages, were quantified for the 6-month pre-WD diagnosis versus the 12-month period after diagnosis. Wilcoxon signed-rank tests and McNemar tests were used to examine incremental differences in burden between cases and controls. Adjusted multivariable generalized linear regression models were used to compare health care burdens. Relative to the 6-month pre-WD diagnosis, the 12 months after diagnosis had more claims per patient (2.87 vs. 3.35; P < 0.0001) and increased per patient health care costs (US $2,089 vs. US $3,887; P < 0.0001). WD cases incurred US $1,908 more in total unadjusted costs compared to controls in the 12-month postindex date monthly averages. The increase in claims was primarily due to outpatient visits (1.62 vs. 1.82) and pharmaceutical claims (1.11 vs. 1.37). Cases also had higher health care costs for inpatient admissions (US $559 vs. US $1,264), outpatient visits (US $770 vs. US $1,037), and pharmaceutical claims (US $686 vs. US $1,489). Conclusion: WD is associated with significant health care cost and use burdens driven by increased inpatient admissions, outpatient visits, and pharmaceutical claims.

Healthcare Utilization and Cost Burden of Porphyria in Commercially Insured Adults in the United States.

OBJECTIVES: The healthcare burden associated with porphyria remains unevaluated despite the associated increased risks of morbidity and mortality. We aimed to assess the healthcare utilization and cost burdens of porphyria in the United States (US) using real-world claims data. METHODS: We performed a case-control analysis of adults in the Truven Health MarketScan® Commercial Claims database (2010-2015). Using propensity scores, 2788 porphyria cases were matched 1:1 to porphyria-free controls with chronic liver disease. Total and service-specific parameters were quantified for the 12 months before porphyria diagnosis versus the 12 months after diagnosis and over the 12 months following a randomly selected date for controls. Wilcoxon signed rank tests and McNemar tests were used to examine incremental differences in burden between cases and controls. Adjusted multivariable generalized linear regression models were used to compare healthcare burdens for cases versus controls. RESULTS: Relative to the 12 months before porphyria diagnosis, the following 12 months had more claims per patient (35.94 vs 39.67; p < 0.0001) and increased per-patient healthcare costs (US$21,308 vs US$27,270; p < 0.0001). Porphyria cases incurred US$7839 more in total unadjusted costs compared with controls in the 12 months after index date. Compared with controls, cases also had more claims (39.67 vs 34.81), primarily due to inpatient admissions (1.80 vs 0.78) and outpatient visits (21.41 vs 17.98). Cases also had higher healthcare costs for inpatient admissions (US$8882 vs US$4674) and outpatient visits (US$12,378 vs US$9801). CONCLUSION: Porphyria is associated with significant healthcare costs and utilization burdens driven by increased inpatient admissions, outpatient visits, and pharmaceutical claims.

Health Care Resource Use and Cost Burden of Chronic Kidney Disease in Patients With Chronic Liver Disease: A Real-World Claims Analysis.

Chronic Liver Disease (CLD) is associated with an increased risk of chronic kidney disease (CKD). However, the health care burden of CKD in the CLD spectrum is unknown. We aimed to evaluate the health care use and cost burdens associated with CKD in patients with CLD in the United States by using real-world claims data. We analyzed data from the Truven Health MarketScan Commercial Claims database from 2010 to 2015. A total of 19,664 patients with CLD with or without comorbid CKD were identified using International Classification of Diseases, Ninth Revision, codes and matched 1:1 by sociodemographic characteristics and comorbidities using propensity scores. Total and service-specific unadjusted and adjusted health care parameters were analyzed for the 12 months following an index date selected at random to capture whole disease burdens. In CLD, comorbid CKD was associated with a higher annual number of claims per person (CKD vs. no CKD, 69 vs. 55) and higher total annual median health care costs (CKD vs. no CKD, $21,397 vs. $16,995). A subanalysis stratified by CKD category showed that health care use and cost burden in CLD increased with disease stage, with a peak 12-month median cost difference of $77,859 in patients on dialysis. The adjusted per person annual health care cost was higher for CKD cases compared to controls ($35,793 vs. $24,048, respectively; P < 0.0001). Stratified by the type of CLD, the highest between-group adjusted cost differences were for cirrhosis, viral hepatitis, hemochromatosis, and nonalcoholic fatty liver disease. Conclusion: CKD is a cost multiplier in CLD. The CKD health care burden in liver disease differs by the type of CLD. Improved CKD screening and proactive treatment interventions for at-risk patients can limit the excess burden associated with CKD in patients with CLD.

The Health Care Burden of Hepatic Encephalopathy.

Hepatic encephalopathy is a major neuropsychiatric complication of liver disease that affects 30% to 40% of cirrhotic patients. Hepatic encephalopathy is characterized by a brain dysfunction that is associated with neurologic complications. Those complications are associated with cognitive impairments, which negatively impacts patients' physical and mental health. In turn, hepatic encephalopathy poses a substantial economic and use burdens to the health care system. This article reviews the multidimensional aspects of the health care burden posed by hepatic encephalopathy.

Social Impact of Hepatic Encephalopathy.

Hepatic encephalopathy (HE) is a multifaceted disorder, with effects stretching far beyond office visits and hospitalizations. Patients with HE suffer from varying degrees of altered consciousness, intellectual disability, and personality changes. A large social impact exists for patients with HE. Quality of life and activities of daily living, such as work capacity, driving ability, and sleep quality, have been shown to be affected. Additionally, caregiver and financial burdens are highly prevalent. Multiple tools exist to assess quality of life, including the CLD-Q questionnaire. Common treatments for HE, including rifaximin and lactulose, have been shown to improve overall quality of life.

Economic and Health Care Burdens of Hepatitis Delta: A Study of Commercially Insured Adults in the United States.

BACKGROUND AND AIMS: The paucity of data regarding the extent of hepatitis delta virus (HDV) associated health care burden in the United States is an important obstacle to assessing the cost-effectiveness of potential intervention strategies. In this study, we characterized the health care use and cost burdens of HDV in the United States using real-world claims data. APPROACH AND RESULTS: We conducted a case-control study using the Truven Health MarketScan Commercial Claims databases from 2011-2014. A total of 2,727 HDV cases were matched 1:1 by sociodemographic characteristics and comorbidities to chronic hepatitis B virus (HBV) controls using propensity scores. The HDV group had significantly higher prevalence of substance abuse, sexually transmitted diseases, decompensated cirrhosis, cirrhosis, and hepatitis C virus compared to patients with chronic HBV. First HDV diagnosis was associated with significant increases in the total number of health care claims (25.61 vs. 28.99; P < 0.0001) and total annual health care costs ($19,476 vs. $23,605; P < 0.0001) compared with pre-HDV baseline. The case-control analysis similarly indicated higher total claims (28.99 vs. 25.19; P < 0.0001) and health care costs ($23,605 vs. $18,228; P < 0.0001) in HDV compared with HBV alone. Compared with HBV controls, HDV cases had an adjusted incident rate ratio of 1.16 (95% confidence interval: 1.10, 1.22) times the total number of annual claims and an adjusted incident rate ratio 1.32 (95% confidence interval 1.17, 1.48) times the total annual health care cost. CONCLUSIONS: HDV is associated with higher health care use and cost burden than HBV alone, underscoring the need for improved screening and treatment.

The burden associated with thrombocytopenia and platelet transfusions among patients with chronic liver disease.

Background: Thrombocytopenia (TCP), a common complication of chronic liver disease (CLD), can cause uncontrolled bleeding during procedures. As such, CLD patients with TCP and platelet counts <50,000/µL often receive prophylactic platelet transfusions before invasive procedures. However, platelet transfusions are associated with clinical complications, which may result in increased healthcare utilization and costs.Objective: This retrospective database analysis describes the clinical and economic burden in CLD patients with TCP, CLD patients without TCP, and CLD patients with TCP who receive platelet transfusions.Methods: Adult CLD patients with or without TCP were identified in the IBM MarketScan Commercial Claims and Medicare Supplemental data from 1 January 2012 to 31 December 2015. CLD patients with or without TCP were propensity-score matched (1:1) for the analysis of annual healthcare utilization and costs. Platelet transfusions among CLD patients with TCP were identified using procedure codes.Results: Of the 601,626 patients with CLD, 8,292 (1.4%) patients with TCP were matched to patients without TCP. Among CLD patients with TCP, 981 (11.8%) patients received ≥1 platelet transfusions and met inclusion/exclusion criteria. Compared to patients without TCP, CLD patients with TCP had more complications, including higher prevalence of neutropenia (11.4% vs 2.9%) and bleeding events (21.4% vs 10.9%), greater resource utilization including greater average hospital admissions (1.2 vs 0.7, p < .01), greater average ER visits (2.1 vs 1.3, p < .01), higher average outpatient office visits (20.1 vs 18.4, p < .01), and higher average healthcare costs including total costs (p < .01), inpatient costs (p < .01), ER visit costs (p < .01), and outpatient office visit costs (p < .01). The mean annual total costs in CLD and TCP patients with platelet transfusions were $206,396.Conclusions: CLD patients with TCP, and particularly those who received platelet transfusions, experienced significantly greater clinical and economic burden compared to CLD patients without TCP. Safer and more cost-effective treatments to increase platelets are necessary.

Health Care Utilization and Economic Burdens of Hemochromatosis in the United States: A Population-Based Claims Study.

BACKGROUND: Little is known about the health care burden of hemochromatosis in the United States, despite its increased morbidity and mortality due to associated advanced liver diseases. OBJECTIVE: To evaluate the health care utilization and economic burdens of hemochromatosis in the United States using real-world claims data. METHODS: We performed a case-control analysis of adult participants in the Truven Health MarketScan Commercial Claims database from 2010 to 2015. 37,092 hemochromatosis cases were matched 1:1 by demographics and comorbidities to hemochromatosis-free controls with chronic liver disease using propensity scores. Total and service-specific health care parameters were quantified for the 12 months following versus the 12 months before the first date of hemochromatosis diagnosis and over the 12 months following a randomly selected date for controls. Incremental differences in health care burdens between cases and controls were examined using Wilcoxon signed rank tests and McNemar tests for continuous and dichotomous measures, respectively. Adjusted multivariable regression analyses using generalized linear models were used to compare the health care burdens for cases with controls. RESULTS: In comparison with the year before, the 12 months following first hemochromatosis diagnoses had a higher total number of claims per patient (34.37 vs. 29.99; P < 0.0001) and an increase in the per-patient total health care costs ($20,023 vs. $16,905; P < 0.0001). After hemochromatosis diagnosis, health care costs were 2%, 8%, 23%, and 43% higher for inpatient admissions, emergency department visits, outpatient visits, and pharmaceutical prescriptions, compared respectively with the 12 months before diagnosis. In the 12 months following the index date, hemochromatosis cases incurred $2,732 more in total unadjusted costs compared with controls. Compared with controls, cases had adjusted incident rate ratio (IRR) 1.26 (95% CI = 1.30-1.77) times the total number of claims (IRR = 1.40, 95% CI = 1.38-1.43) more outpatient visits and IRR = 1.10 (95% CI = 1.08-1.11) excess pharmaceutical claims. Compared with controls, cases had significantly higher adjusted mean health care costs for inpatient services ($6,484 vs. $7,854), outpatient services ($7,032 vs. $11,005), and pharmaceutical claims ($2,520 vs. $2,822; all P values < 0.05). The annual health care costs among type 2 diabetes, hypertension, arthritis, and chronic kidney disease (CKD) patients with hemochromatosis were $6,968, $7,424, $2,967, and $43,847, respectively, higher than type 2 diabetes, hypertension, arthritis, and CKD patients without hemochromatosis (P < 0.0001). CONCLUSIONS: Hemochromatosis in the United States is associated with significant health care utilization and economic burdens driven by outpatient visits, pharmaceutical claims, and a high number of comorbidities DISCLOSURES: No outside funding supported this study. The authors have no relevant financial or other relationships to disclose. An abstract containing some of the results from this study was accepted for the American Association for the Study of Liver Diseases Meeting; November 9-13, 2018; San Francisco, CA.

Disparities in hepatitis A virus (HAV) vaccination coverage among adult travelers to intermediate or high-risk countries: The role of birthplace and race/ethnicity.

BACKGROUND: While the hepatitis A virus (HAV) vaccine is recommended for United States (US) travelers to endemic regions, vaccination rates are lower among non-US-born adults and some racial minority groups. PURPOSE: We aimed to examine the relationship between birthplace, race and their interaction as predictors of self-reported HAV vaccination among adult travelers to high-risk countries (HRCs) through analysis of the National Health Interview Survey (NHIS), 2012-2015. METHODS: The study included 36,872 US adult participants in the 2012-2015 NHIS who traveled to countries where HAV is endemic. The main outcome was self-reported HAV vaccination (≥2 doses). Complex survey methods were applied to all models to provide statistical estimates that were representative of US adults. Multivariable logistic regression models adjusting for demographic, socioeconomic, medical, and access-to-care characteristics were fitted to examine the association between birthplace, race, race-by-birthplace (for interaction) and vaccination status. RESULTS: For adult travelers to HRCs, the adjusted odds ratio (AOR) of HAV vaccination was lower for non-US-born compared to US-born adults, AOR 0.86 (95% CI; 0.76, 0.98). For Hispanics, the AOR of HAV vaccination was 0.80 (95% CI; 0.70, 0.91) as compared to non-Hispanic-Whites. Furthermore, a significant qualitative interaction between birthplace and race was found (P-value 0.0005). Among non-Hispanic Blacks, the adjusted odds of HAV vaccination for non-US-born adults were 1.35 (95% CI; 1.06, 1.72) times the odds for US-born adults. In contrast, the AORs of HAV vaccination of non-US-born versus US-born adults were 36% (95% CI; 17%, 51%) and 30% (95% CI; 12%, 44%), lower for Asians and Hispanics, respectively. CONCLUSIONS: The association between birthplace and HAV vaccination status differs by race among travelers to HRCs, with US-born non-Hispanic Black and non-US-born Asian and Hispanic adults having lower odds of vaccination. Health care resources should be focused on these target populations to improve travel vaccination compliance.

Cost-effectiveness of new antiviral regimens for treatment-naïve U.S. veterans with hepatitis C.

UNLABELLED: Recently approved, interferon-free medication regimens for treating hepatitis C are highly effective, but extremely costly. We aimed to identify cost-effective strategies for managing treatment-naïve U.S. veterans with new hepatitis C medication regimens. We developed a Markov model with 1-year cycle length for a cohort of 60-year-old veterans with untreated genotype 1 hepatitis C seeking treatment in a typical year. We compared using sofosbuvir/ledipasvir or ombitasvir/ritonavir/paritaprevir/dasabuvir to treat: (1) any patient seeking treatment; (2) only patients with advanced fibrosis or cirrhosis; or (3) patients with advanced disease first and healthier patients 1 year later. The previous standard of care, sofosbuvir/simeprevir or sofosbuvir/pegylated interferon/ribavirin, was included for comparison. Patients could develop progressive fibrosis, cirrhosis, or hepatocellular carcinoma, undergo transplantation, or die. Complications were less likely after sustained virological response. We calculated the incremental cost per quality-adjusted life year (QALY) and varied model inputs in one-way and probabilistic sensitivity analyses. We used the Veterans Health Administration perspective with a lifetime time horizon and 3% annual discounting. Treating any patient with ombitasvir-based therapy was the preferred strategy ($35,560; 14.0 QALYs). All other strategies were dominated (greater costs/QALY gained than more effective strategies). Varying treatment efficacy, price, and/or duration changed the preferred strategy. In probabilistic sensitivity analysis, treating any patient with ombitasvir-based therapy was cost-effective in 70% of iterations at a $50,000/QALY threshold and 65% of iterations at a $100,000/QALY threshold. CONCLUSION: Managing any treatment-naïve genotype 1 hepatitis C patient with ombitasvir-based therapy is the most economically efficient strategy, although price and efficacy can impact cost-effectiveness. It is economically unfavorable to restrict treatment to patients with advanced disease or use a staged treatment strategy. (Hepatology 2016;63:428-436).

Impact of adverse events on costs and quality of life in protease inhibitor-based combination therapy for hepatitis C.

Protease inhibitor with pegylated interferon and ribavirin therapy (PI-PR) increases hepatitis C virus treatment efficacy versus standard of care pegylated interferon and ribavarin therapy [PR]. The adverse event (AE) impact of PI-PR remains under-reported. The authors estimated the AE impact on costs, treatment discontinuation and health-related quality of life (HRQoL) in PI-PR- and PR-treated patients through literature review and cost analysis. HRQoL and safety data were synthesized by instrument, AE and discontinuation rate. AE-related treatment costs were estimated with trial-based AE rates and literature-based protocols, resource utilization and standard costs. No PI-PR study reported HRQoL outcomes. Five PR studies reported that anemia, depression, fatigue and/or influenza-like symptoms negatively affected HRQoL. Decreased HRQoL predicted treatment discontinuation in two PR studies. PI-PR and PR had comparable AE-related treatment discontinuation rates (~12%). Weighted AE-related treatment costs were US$2042, $1835 and $1076 in boceprevir-based PI-PR, PR and telaprevir-based PI-PR, respectively. AE-related burden may increase with PI-PR. Future studies should incorporate AE-related economic and HRQoL outcomes to comprehensively assess costs/benefits.