Cost of illness of Primary Biliary Cholangitis - a population-based study.

BACKGROUND: The economic burden of Primary Biliary Cholangitis (PBC) has not been investigated at population-level. Aim of this study was to estimate the cost of illness of PBC in Lombardy, Italy. METHODS: Individuals with PBC were identified through ICD-9-CM code 571.6 and/or medical exemption code 008.571.6, from the Banca Dati Assistito of Lombardy. Only health services (outpatient, inpatient activities and drugs) related to PBC were considered to estimate direct medical costs in 2017. RESULTS: We identified 970 adult patients (83.5% females) with a mean age of 61 years. Global annual costs were equal to € 913,763 (€ 942 per patient), with € 459,506 (50.3%, € 474 per patient) deriving from hospitalizations (mostly due to liver transplantation, 30.5%, and cirrhosis complications, 20.6%). Costs from outpatient activities were € 109,090 (11.9%, € 112 per patient). CONCLUSIONS: This study provides an overview of the costs attributed to PBC care and management, mainly related to hospitalizations for cirrhosis complications, which is necessary for assuring cost-effective introduction of novel therapies. Additional studies focused on indirect cost, e.g. overall loss of productivity, are warranted.

Race/Ethnicity and Insurance-Specific Disparities in In-Hospital Mortality Among Adults with Primary Biliary Cholangitis: Analysis of 2007-2014 National Inpatient Sample.

BACKGROUND: Primary biliary cholangitis (PBC) is a progressive autoimmune liver disease that can result in cirrhosis and end-stage liver disease. AIMS: We aim to evaluate hospitalization burden and in-hospital mortality among PBC patients in the USA. METHODS: Using data from the Nationwide Inpatient Sample from 2007 to 2014, hospitalizations among US adults with PBC were stratified by sex, age, and race/ethnicity. Overall in-hospital mortality was stratified by these variables and adjusted multivariate regression models evaluated for predictors of in-hospital mortality. RESULTS: From 2007 to 2014, there were 18,279 hospitalizations among adults with PBC (15.0% male, mean age 63.8 years, 41.3% cirrhosis). Among non-Hispanic whites, the proportion of total PBC hospitalizations increased from 57.8% in 2007 to 71.2% in 2014, compared to 4.1-6.3% for African-Americans, 8.6-10.9% for Hispanics, and 1.7-2.8% for Asians (p < 0.001 for all). While overall in-hospital mortality was low (4.2%), increasing age was associated with higher odds of in-hospital mortality (OR: 1.02, 95% CI 1.01-1.03, p < 0.001). Compared to non-Hispanic white PBC patients, higher in-hospital mortality was observed in African-American PBC patients (OR: 1.40, 95% CI 1.16-2.03, p < 0.05). Compared to patients with private/commercial insurance, significantly higher odds of in-hospital mortality were observed in patients with Medicaid insurance (OR 1.42, 95% CI 1.00-1.99, p < 0.05). CONCLUSION: In summary, among adults with PBC hospitalized in the USA from 2007 to 2014, the overall number of hospitalizations is increasing. Significant disparities in in-hospital mortality were observed; African-Americans with PBC and Medicaid patients with PBC have disproportionately higher odds of in-hospital mortality.

Population-based epidemiology of primary biliary cirrhosis in South Korea.

BACKGROUND: As a rare disease, only a few population-based epidemiology studies of primary biliary cirrhosis (PBC) have been reported. AIMS: To elucidate the nationwide prevalence, incidence, complications, fatality and direct medical costs of PBC in South Korea. METHODS: The nationwide Health Insurance Review and Assessment Service claims data and Rare Intractable Disease registration data on PBC, identified with the International Classification of Diseases (ICD) 10 code of K74.3, were obtained from 2009 to 2013. Age- and gender-specific prevalence and incidence rates of PBC were calculated, and data on complications, comorbidities, prescribed drugs, therapeutic procedures and direct medical costs were analysed. RESULTS: A total of 2824 patients over 20 years old with PBC were identified in 2009-2013 (female-to-male ratio 6.2, median age 57 years old). The average age- and sex-adjusted incidence from 2011 to 2013 was 8.57 per million per year, and the average age- and sex-adjusted prevalence from 2009 to 2013 was 47.50 per million population. About 10% of patients presented with complications such as ascites (10.3%), variceal bleeding (5.8%) and/or hepatocellular carcinoma (HCC) (1.3%). Liver transplantation was undertaken in 71 patients (2.5%) for 5 years. Case fatality was 2.2% and the transplantation-free survival was 95.4% for 5 years. CONCLUSIONS: This is the first report on the nationwide epidemiology of primary biliary cirrhosis in South Korea, demonstrating lower incidence and prevalence rates than those of Western countries, but a considerable disease burden, representing at least 10% were complicated with decompensated cirrhosis or hepatocellular carcinoma requiring liver transplantation.

Cost and health consequences of treatment of primary biliary cirrhosis with ursodeoxycholic acid.

BACKGROUND: Long-term use of ursodeoxycholic acid (UDCA) is the recommended therapy in primary biliary cirrhosis (PBC). The lifetime effectiveness and cost-effectiveness of UDCA in PBC have, however, not been assessed. AIM: To estimate the health outcomes and lifetime costs of a Norwegian cohort of PBC patients on UDCA. METHODS: Norwegian PBC patients (n = 182) (90% females; mean age 56.3 ± 8.9 years; Mayo risk score 4.38) who were included in a 5-year open-label study of UDCA therapy were subsequently followed up for up to 11.5 years. The lifetime survival was estimated using a Weibull survival model. The survival benefit from UDCA was based on a randomised clinical trial from Canada, comparing the effect of non-UDCA and UDCA. Survival and costs of standard care vs. standard care plus UDCA were simulated in a Markov model with death and liver transplantation as major events, invoking transition of a patient's state in the model. RESULTS: The gain in life expectancy for a PBC patient on UDCA compared with standard care was 2.24 years (1.19 years discounted). The lifetime treatment costs were EUR 151,403 and EUR 157,741 (EUR 102,912 and EUR 115,031 discounted) for patients with and without UDCA respectively. A probabilistic sensitivity analysis indicated an 82% probability that UDCA entails both greater life expectancy and lower costs than standard care. CONCLUSIONS: The results of this study indicate that UDCA therapy is a dominant strategy as it confers reduced morbidity and mortality, as well as cost savings, compared with standard therapy.

Cost of a quality-adjusted life year in liver transplantation: the influence of the indication and the model for end-stage liver disease score.

Cost issues in liver transplantation (LT) have received increasing attention, but the cost-utility is rarely calculated. We compared costs per quality-adjusted life year (QALY) from the time of placement on the LT waiting list to 1 year after transplantation for 252 LT patients and to 5 years after transplantation for 81 patients. We performed separate calculations for chronic liver disease (CLD), acute liver failure (ALF), and different Model for End-Stage Liver Disease (MELD) scores. For the estimation of QALYs, the health-related quality of life was measured with the 15D instrument. The median costs and QALYs after LT were €141,768 and 0.895 for 1 year and €177,618 and 3.960 for 5 years, respectively. The costs of the first year were 80% of the 5-year costs. The main cost during years 2 to 5 was immunosuppression drugs (59% of the annual costs). The cost/QALY ratio improved from €158,400/QALY at 1 year to €44,854/QALY at 5 years, and the ratio was more beneficial for CLD patients (€42,500/QALY) versus ALF patients (€63,957/QALY) and for patients with low MELD scores versus patients with high MELD scores. Although patients with CLD and MELD scores > 25 demonstrated markedly higher 5-year costs (€228,434) than patients with MELD scores < 15 (€169,541), the cost/QALY difference was less pronounced (€59,894/QALY and €41,769/QALY, respectively). The cost/QALY ratio for LT appears favorable, but it is dependent on the assessed time period and the severity of the liver disease.

Antimitochondrial antibody negative primary biliary cirrhosis in Japan: utilization of clinical data when patients applied to receive public financial aid.

BACKGROUND: We examined patients who showed laboratory and histological evidence of primary biliary cirrhosis (PBC) in the absence of antimitochondrial antibody (AMA) to elucidate the characteristics of AMA negative PBC. METHODS: From a total of 5,805 patients with symptomatic PBC, 2,419 cases (41.7%) were selected in the present study, who were diagnosed using the following criterion; chronic non-suppurative destructive cholangitis was histologically observed and laboratory data did not contradict PBC. The information collected from records included sex, age, symptoms, physical findings, and complicated autoimmune diseases. We then evaluated these data according to the positivity of AMA. RESULTS: Of the total subjects, 470 cases (19.4%) were found to be negative for AMA. The proportion of female patients was higher among the AMA negative group than among the AMA positive one. Pruritus was found less frequently among patients with AMA negative PBC than among those with AMA positive PBC. Levels of alkaline phosphatase,gamma-glutamyl transpeptidase, and IgM were significantly lower among patients with AMA negative PBC than among those with AMA positive PBC. Complications such as Sjögren's syndrome, rheumatoid arthritis, and scleroderma, including CREST syndrome, were found with significantly higher frequency among patients with AMA negative PBC than among those with AMA positive PBC. CONCLUSION: Considering serum level of IgM and frequencies of complicated autoimmune diseases, it is possible that Japanese patients with AMA negative PBC are consistent with the disease entity of autoimmune cholangitis reported in western countries.

Determining priority for liver transplantation: a comparison of cost per QALY and discrete choice experiment-generated public preferences.

OBJECTIVE: A comparison of the implications of the application of the principles of equity and efficiency as two desirable but competing attributes of the organ allocation system. Efficiency is defined in economic terms as the standard cost per QALY model and equity considerations are included in a model based on public preferences generated from a discrete choice experiment in determining priority for donor liver graft allocation. METHODS: A survey of the general public (n = 303) using a discrete choice experiment was undertaken. The results enabled estimation of the relative weights attached to several key factors which might be used to prioritise patients on the waiting list for liver transplantation. These weights were then used to develop a patient-specific index (PSI) for all patients diagnosed with one of three main chronic liver diseases who had received a liver transplant during an 18-month period at all Department of Health designated liver transplant centres in England and Wales (n = 207). The cost per QALY model comprised net total costs from assessment to 27 months following assessment as the numerator of the ratio. Net survival over the same time period, adjusted for HR-QOL using population values for the EQ-5D descriptive system, formed the denominator. RESULTS: Priority for liver transplantation differed markedly according to whether patients were ranked according to efficiency (net cost per QALY) or equity considerations (PSI) and the differences in ranks were found to be statistically significant (Wilcoxon signed rank test p < 0.001). CONCLUSIONS: This study emphasises that the priorities of the general public may not accord with those arising from a pure efficiency objective and quantifies the extent of the efficiency loss in terms of lost QALYs and increased net programme costs associated with the incorporation of equity concerns as reflected in public preferences for the allocation of donor livers for transplantation.

Midterm cost-effectiveness of the liver transplantation program of England and Wales for three disease groups.

Liver transplantation has never been the subject of a randomized controlled trial, and there remains uncertainty about the magnitude of benefit and cost-effectiveness for specific patient groups. This article reports the results of an economic evaluation of adult liver transplantation in England and Wales. Patients placed on the waiting list for a liver transplant were observed over 27 months. The costs and health benefits of a comparison group, representing experience in the absence of liver transplantation, were estimated using a combination of observed data from patients waiting for a transplant and published prognostic models. The analysis focuses on three disease groups, for each of which prognostic models were available: primary biliary cirrhosis (PBC), alcoholic liver disease (ALD), and primary sclerosing cholangitis (PSC). A higher proportion of patients with ALD were assessed for a transplant but not placed on the waiting list. The estimated gain in quality-adjusted life-years from transplantation was positive for each of the disease groups. The mean incremental cost per quality-adjusted life-year (95% bootstrap confidence intervals) from time of listing to 27 months for patients with PBC, ALD, and PSC are pound 29,000 (pounds 1,000 to pounds 59,000), pounds 48,000 (pounds 12,000 to pounds 83,000) and pounds 21,000 (-pounds 23,000 to pounds 60,000), respectively. In conclusion, liver transplantation increases the survival and health-related quality of life of patients with each of three end-stage liver diseases. However, the extent of this increase differs between different disease groups. Cost-effectiveness estimates were poorer for patients with ALD over the 27-month period than for patients with PBC or PSC. This in part reflects the costs of the higher number of ALD patients assessed for each transplant.

Factors associated with the high cost of liver transplantation in adults.

OBJECTIVES: To determine the overall direct cost of liver transplantation in Canadian adults and to identify the factors that are associated with high cost. METHODS: The direct cost of liver transplantation from the perspective of third-party payers was determined in a retrospective analysis of data from hospital charts and databases. A consecutive series of 119 adults who underwent liver transplantation between 1991 and 1992 was followed from the date of listing for transplantation to the second anniversary of the transplant. Patient-specific services during the pre-transplantation, transplantation and post-transplantation phases were compiled and costed. The primary consideration was the impact of complications on the cost of transplantation. Secondary considerations were the impact of age, sex of the patient, diagnosis and severity of liver disease on the total cost. RESULTS: The overall mean measured cost of liver transplantation was Can$89,066 (range from Can$30,505-Can$690,431). The multivariate logistic regression model for overall costs revealed that severe liver disease (OR = 11.97), cytomegalovirus infection (OR = 6.12), additional operative procedure (OR = 4.22) and biliary complications (OR = 5.00) were associated with an increased likelihood of high cost. The addition of services that were not measured in the present analysis increased the total overall cost to a mean of $121,732 (1998 Canadian dollars, follow-up costs discounted and inflation adjusted). INTERPRETATION: The factors that were associated with high cost of liver transplantation in Canadian adults were advanced liver disease, postoperative cytomegalovirus infection, the requirement for additional operative procedures and biliary complications.

Medical and economic impact of autoimmune hepatitis.

AIH is a chronic liver disease that has been associated with hepatic failure and death in the absence of liver transplantation. As a result, AIH imparts significant medical and economic burdens on affected patients and health care delivery systems, respectively. The use of accepted methodologies for outcomes and health services research has identified emerging information on the epidemiology and natural history, HRQoL, and resource utilization for similar autoimmune chronic liver diseases such as PBC and PSC. Similar efforts are needed in AIH, and they are supported on the basis of existing data which suggest similar levels of disease burden compared to PBC and PSC. As a result, the ability to plan for disease management strategies in AIH that require the allocation of scarce resources will be feasible.

Cost-effectiveness of ursodeoxycholic acid therapy in primary biliary cirrhosis.

Ursodeoxycholic acid (UDCA) is a safe and effective treatment for patients with primary biliary cirrhosis (PBC), but the cost of this drug has raised concerns regarding cost-effectiveness. The aim of our study was to determine the cost-effectiveness of UDCA in PBC. We compared the costs and outcomes of managing PBC patients with and without UDCA. From two previously published trials, the effectiveness of UDCA was determined by comparing the annual reduction in the development of ascites, varices, variceal bleeding, encephalopathy, liver transplantation, and death between the treatment groups. Average annual costs for each of these events were estimated based on literature and institutional data. Approximately twice as many major events occurred in the placebo group compared with the UDCA group. The relative risk (RR) of liver transplantation (1.95; 95% CI: 1.14-3.68) and development of esophageal varices (3. 11; 95% CI: 1.57-10.65) were significantly higher in the placebo group compared with the UDCA group. There were no significant increases in the RR of ascites, variceal bleeding, encephalopathy, or death between the two groups. Based on the estimated annual cost of managing these events and the annual costs of UDCA ($2,500), there was an annual cost savings per patient of $1,372. Compared with the placebo group, patients receiving UDCA had a lower incidence of major complications and lower medical care costs.