Underfunding of German university-based high-performance medicine exemplified by the treatment of varices in cirrhosis.

Facing increasing economization in the health care sector, clinicians have to adapt not only to the ever-growing economic challenges, but also to a patient-oriented health care. Treatment costs are the most important variable for optimizing success when facing scarce human resources, increasing material- and infrastructure costs in general, as well as low revenue flexibility due to flat rates per case in Germany, the so-called Diagnosis-Related Groups (DRG). University hospitals treat many patients with particularly serious illnesses. Therefore, their share of complex and expensive treatments, such as liver cirrhosis, is significantly higher. The resulting costs are not adequately reflected in the DRG flat rate per case, which is based on an average calculation across all hospitals, which increases this economic pressure. Thus, the aim of this manuscript is to review cost and revenue structures of the management of varices in patients with cirrhosis at a university center with a focus on hepatology. For this monocentric study, the data of 851 patients, treated at the Gastroenterology Department of a University Hospital between 2016 and 2020, were evaluated retrospectively and anonymously. Medical services (e.g., endoscopy, radiology, laboratory diagnostics) were analyzed within the framework of activity-based-costing. As part of the cost unit accounting, the individual steps of the treatment pathways of the 851 patients were monetarily evaluated with corresponding applicable service catalogs and compared with the revenue shares of the cost center and cost element matrix of the German (G-) DRG system. This study examines whether university-based high-performance medicine is efficient and cost-covering within the framework of the G-DRG system. We demonstrate a dramatic underfunding of the management of varicose veins in cirrhosis in our university center. It is therefore generally questionable whether and to what extent an adequate care for this patient collective is reflected in the G-DRG system.

Cost effectiveness of hepatitis C direct acting agents.

INTRODUCTION: Introduction of direct acting antivirals (DAA) has transformed treatment of chronic hepatitis C (HCV) and made the elimination of HCV an achievable goal set forward by World Health Organization by 2030. Multiple barriers need to be overcome for successful eradication of HCV. Availability of pan-genotypic HCV regimens has decreased the need for genotype testing but maintained high efficacy associated with DAAs. AREAS COVERED: In this review, we will assess the cost-effectiveness of DAA treatment in patients with chronic HCV disease, with emphasis on general, cirrhosis, and vulnerable populations. EXPERT OPINION: Multiple barriers exist limiting eradication of HCV, including cost to treatment, access, simplified testing, and implementing policy to foster treatment for all groups of HCV patients. Clinically, DAAs have drastically changed the landscape of HCV, but focused targeting of vulnerable groups is needed. Public policy will continue to play a strong role in eliminating HCV. While we will focus on the cost-effectiveness of DAA, several other factors regarding HCV require on going attention, such as increasing public awareness and decreasing social stigma associated with HCV, offering universal screening followed by linkage to treatment and improving preventive interventions to decrease spread of HCV.

LiverRisk score: An accurate, cost-effective tool to predict fibrosis, liver-related, and diabetes-related mortality in the general population.

BACKGROUND: Noninvasive and early assessment of liver fibrosis is of great significance and is challenging. We aimed to evaluate the predictive performance and cost-effectiveness of the LiverRisk score for liver fibrosis and liver-related and diabetes-related mortality in the general population. METHODS: The general population from the NHANES 2017-March 2020, NHANES 1999-2018, and UK Biobank 2006-2010 were included in the cross-sectional cohort (n = 3,770), along with the NHANES follow-up cohort (n = 25,317) and the UK Biobank follow-up cohort (n = 17,259). The cost-effectiveness analysis was performed using TreeAge Pro software. Liver stiffness measurements ≥10 kPa were defined as compensated advanced chronic liver disease (cACLD). FINDINGS: Compared to conventional scores, the LiverRisk score had significantly better accuracy and calibration in predicting liver fibrosis, with an area under the receiver operating characteristic curve (AUC) of 0.76 (0.72-0.79) for cACLD. According to the updated thresholds of LiverRisk score (6 and 10), we reclassified the population into three groups: low, medium, and high risk. The AUCs of LiverRisk score for predicting liver-related and diabetes-related mortality at 5, 10, and 15 years were all above 0.8, with better performance than the Fibrosis-4 score. Furthermore, compared to the low-risk group, the medium-risk and high-risk groups in the two follow-up cohorts had a significantly higher risk of liver-related and diabetes-related mortality. Finally, the cost-effectiveness analysis showed that the incremental cost-effectiveness ratio for LiverRisk score compared to FIB-4 was USD $18,170 per additional quality-adjusted life-year (QALY) gained, below the willingness-to-pay threshold of $50,000/QALY. CONCLUSIONS: The LiverRisk score is an accurate, cost-effective tool to predict liver fibrosis and liver-related and diabetes-related mortality in the general population. FUNDING: The National Natural Science Foundation of China (nos. 82330060, 92059202, and 92359304); the Key Research and Development Program of Jiangsu Province (BE2023767a); the Fundamental Research Fund of Southeast University (3290002303A2); Changjiang Scholars Talent Cultivation Project of Zhongda Hospital of Southeast University (2023YJXYYRCPY03); and the Research Personnel Cultivation Program of Zhongda Hospital Southeast University (CZXM-GSP-RC125).

Societal costs and survival of patients with biopsy-verified non-alcoholic steatohepatitis: Danish nationwide register-based study.

INTRODUCTION AND OBJECTIVES: Studies on the societal burden of patients with biopsy-confirmed non-alcoholic fatty liver disease (NAFLD) are sparse. This study examined this question, comparing NAFLD with matched reference groups. MATERIALS AND METHODS: Nationwide Danish healthcare registers were used to include all patients (≥18 years) diagnosed with biopsy-verified NAFLD (1997-2021). Patients were classified as having simple steatosis or non-alcoholic steatohepatitis (NASH) with or without cirrhosis, and all matched with liver-disease free reference groups. Healthcare costs and labour market outcomes were compared from 5 years before to 11 years after diagnosis. Patients were followed for 25 years to analyse risk of disability insurance and death. RESULTS: 3,712 patients with biopsy-verified NASH (n = 1,030), simple steatosis (n = 1,540) or cirrhosis (n = 1,142) were identified. The average total costs in the year leading up to diagnosis was 4.1-fold higher for NASH patients than the reference group (EUR 6,318), 6.2-fold higher for cirrhosis patients and 3.1-fold higher for simple steatosis patients. In NASH, outpatient hospital contacts were responsible for 49 % of the excess costs (EUR 3,121). NASH patients had statistically significantly lower income than their reference group as early as five years before diagnosis until nine years after diagnosis, and markedly higher risk of becoming disability insurance recipients (HR: 4.37; 95 % CI: 3.17-6.02) and of death (HR: 2.42; 95 % CI: 1.80-3.25). CONCLUSIONS: NASH, simple steatosis and cirrhosis are all associated with substantial costs for the individual and the society with excess healthcare costs and poorer labour market outcomes.

Cost-Effectiveness Analysis of Hepatocellular Carcinoma Surveillance in Nonalcoholic Fatty Liver Disease Cirrhosis Using US Visualization Score C-Triggered Abbreviated MRI.

INTRODUCTION: Ultrasound (US) is associated with severe visualization limitations (US Liver Imaging Reporting and Data System visualization score C) in one-third of patients with nonalcoholic fatty liver disease (NAFLD) cirrhosis undergoing hepatocellular carcinoma (HCC) screening. Data suggest abbreviated MRI (aMRI) may improve HCC screening efficacy. This study analyzed the cost-effectiveness of HCC screening strategies, including an US visualization score-based approach with aMRI, in patients with NAFLD cirrhosis. METHODS: We constructed a Markov model simulating adults with compensated NAFLD cirrhosis in the United States undergoing HCC screening, comparing strategies of US plus visualization score, US alone, or no surveillance. We modeled aMRI in patients with visualization score C and negative US, while patients with scores A/B did US alone. We performed a sensitivity analysis comparing US plus visualization score with US plus alpha fetoprotein or no surveillance. The primary outcome was the incremental cost-effectiveness ratio (ICER), with a willingness-to-pay threshold of $100,000 per quality-adjusted life-year. Sensitivity analyses were performed for all variables. RESULTS: US plus visualization score was the most cost-effective strategy, with an ICER of $59,005 relative to no surveillance. The ICER for US alone to US plus visualization score was $822,500. On sensitivity analysis, screening using US plus visualization score remained preferred across several parameters. Even with alpha fetoprotein added to US, the US plus visualization score strategy remained cost-effective, with an ICER of $62,799 compared with no surveillance. DISCUSSION: HCC surveillance using US visualization score-based approach, using aMRI for visualization score C, seems to be the most cost-effective strategy in patients with NAFLD cirrhosis.

Differences in the pattern and cost of hospital care between Indigenous and non-Indigenous Australians with cirrhosis: an exploratory study.

BACKGROUND: Liver diseases are important contributors to the mortality gap between Indigenous and non-Indigenous Australians. AIMS: This cohort study examined factors associated with hospital admissions and healthcare outcomes among Indigenous Australians with cirrhosis. METHODS: Patient-reported outcomes were obtained by face-to-face interview (Chronic Liver Disease Questionnaire and Short Form 36 (SF-36)). Clinical data were extracted from medical records and through data linkage for 534 patients (25 indigenous). Cumulative overall survival (Kaplan-Meier), rates of hospital admissions and emergency presentations, and costs were assessed by indigenous status. Incidence rate ratios (IRR; Poisson regression) were reported. RESULTS: Indigenous Australians admitted to hospital with cirrhosis had lower educational status compared with non-indigenous patients (79.2% vs 43.4%; P < 0.001). The two groups had, in general, similar clinical characteristics including disease severity (P = 0.78), presence of cirrhosis complications (P = 0.67), comorbidities (P = 0.62), rates of cirrhosis-related admissions (P = 0.86) and 5-year survival (P = 0.30). However, indigenous patients had a lower score in the SF-36 domain related to bodily pain (P = 0.037), more cirrhosis admissions via the emergency department (IRR = 1.42, 95% confidence interval (CI) 1.10-1.83) and fewer planned cirrhosis admissions (IRR = 0.32, 95% CI 0.14-0.72). The total cost for cirrhosis-related hospital admissions for 534 patients over 6 years (July 2012 to June 2018) was A$13.7 million. The cost of cirrhosis-related hospital admissions was double for indigenous patients (cost ratio = 2.04, 95% CI 2.04-2.05). CONCLUSIONS: Our data highlight the disparities in health service use and patient-reported outcomes, despite having similar clinical profiles. Integration between primary care, Aboriginal Community Controlled Health Organisations and liver specialists is critical for appropriate health service delivery and effective use of resources. Chronic liver disease costs the community dearly.

In-patient Expenditure Between 2012 and 2020 Concerning Patients With Liver Cirrhosis in Chongqing: A Hospital-Based Multicenter Retrospective Study.

Background: Liver cirrhosis is a major global health and economic challenge, placing a heavy economic burden on patients, families, and society. This study aimed to investigate medical expenditure trends in patients with liver cirrhosis and assess the drivers for such medical expenditure among patients with liver cirrhosis. Methods: Medical expenditure data concerning patients with liver cirrhosis was collected in six tertiary hospitals in Chongqing, China, from 2012 to 2020. Trends in medical expenses over time and trends according to subgroups were described, and medical expenditure compositions were analyzed. A multiple linear regression model was constructed to evaluate the factors influencing medical expenditure. All expenditure data were reported in Chinese Yuan (CNY), based on the 2020 value, and adjusted using the year-specific health care consumer price index for Chongqing. Results: Medical expenditure for 7,095 patients was assessed. The average medical expenditure per patient was 16,177 CNY. An upward trend in medical expenditure was observed in almost all patient subgroups. Drug expenses were the largest contributor to medical expenditure in 2020. A multiple linear regression model showed that insurance type, sex, age at diagnosis, marital status, length of stay, smoking status, drinking status, number of complications, autoimmune liver disease, and the age-adjusted Charlson comorbidity index score were significantly related to medical expenditure. Conclusion: Conservative estimates suggest that the medical expenditure of patients with liver cirrhosis increased significantly from 2012 to 2020. Therefore, it is necessary to formulate targeted measures to reduce the personal burden on patients with liver cirrhosis.

Burden of compensated and decompensated cirrhosis: real world data from an Italian population-based cohort study.

OBJECTIVE: To quantify the annual healthcare resource utilization, costs and mortality rate for a large cohort of Italian patients with compensated (CC) and decompensated cirrhosis (DC). PATIENTS AND METHODS: A population-based cohort study was conducted through the data-linkage of mortality for all-cause, hospitalizations and outpatient drugs and service databases of the Campania Region. All adults hospitalized with cirrhosis diagnosis (2007-2015) were grouped in CC and DC (prevalent patients) on January 1, 2016 and followed for 1-year. Incident patients with DC (2015) were also retrieved and followed from discharge date up to 1-year. Negative binomial regression was used to estimate Incidence Rate Ratios (IRRs) for predictors of all-cause hospitalizations. Costs were evaluated from the Italian National Health Service perspective and expressed in euro patient/year. RESULTS: A total of 21,433 prevalent cirrhotic patients (57.1% CC and 42.9% DC) and 1,371 incident patients with DC were identified. During a 1-year, 21.5% of prevalent patients with CC were admitted for acute events, 26.8% of those with DC and 55.4% of incident patients with DC. Ascites (IRR=1.71;95% CI: 1.37-2.14) and hepatic encephalopathy (IRR=1.35; 95% CI: 1.04-1.77) at index admission were strong predictors of hospitalizations in incident DC patients. The 1-year mortality rate was respectively 5.8% and 10.1% for prevalent patients with CC and DC and 35.6% for incident patients with DC. Direct costs amounted to 3,194€ patient/year for the prevalent CC group and 4,001€ patient/year for the DC group and 13,806 € patient/year for incident individuals with DC. CONCLUSIONS: The burden of cirrhosis dramatically differs between CC and DC patients, especially after the first decompensation episode. Ascites and hepatic encephalopathy at index admission were strong predictors of hospitalizations in incident DC patients.

The global burden of cirrhosis: A review of disability-adjusted life-years lost and unmet needs.

Cirrhosis is a burden on the individual and on public health. The World Health Organization's metric of public health burden is the disability-adjusted life-year (DALY), the sum of years of life lost due to premature death and years of life lived with disability. The more DALYs attributable to a disease, the greater its burden on public health. Cirrhosis was responsible for 26.8% fewer DALYs in 2019 than in 1990, which is positive, but the reduction in DALYs across the spectrum of diseases in and outside the liver was 34.4%. Hepatitis C (26% of DALYs), alcohol (24%), and hepatitis B (23%) contribute almost equally to the global burden of cirrhosis. The contribution from non-alcoholic fatty liver disease (8%) is small but increasing. There is substantial global variation in the burden and causes of cirrhosis. We find that the poorest countries carry the greatest burden of cirrhosis, and that this burden is primarily caused by cirrhosis from hepatitis B infection. Interventions targeting hepatitis B infection are known, but not fully implemented. In more affluent countries, alcohol and hepatitis C are the dominant causes of cirrhosis, but non-alcoholic fatty liver will likely become a dominant cause of cirrhosis in parallel with the increasing prevalence of obesity. We also argue that the World Health Organization underestimates the public health burden associated with cirrhosis because it assigns zero disability to compensated cirrhosis and considers decompensated cirrhosis as only mildly disabling.

Modelling the cost effectiveness of non-alcoholic fatty liver disease risk stratification strategies in the community setting.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent worldwide. Identifying high-risk patients is critical to best utilize limited health care resources. We established a community-based care pathway using 2D ultrasound shear wave elastography (SWE) to identify high risk patients with NAFLD. Our objective was to assess the cost-effectiveness of various non-invasive strategies to correctly identify high-risk patients. METHODS: A decision-analytic model was created using a payer's perspective for a hypothetical patient with NAFLD. FIB-4 [≥1.3], NAFLD fibrosis score (NFS) [≥-1.455], SWE [≥8 kPa], transient elastography (TE) [≥8 kPa], and sequential strategies with FIB-4 or NFS followed by either SWE or TE were compared to identify patients with either significant (≥F2) or advanced fibrosis (≥F3). Model inputs were obtained from local data and published literature. The cost/correct diagnosis of advanced NAFLD was obtained and univariate sensitivity analysis was performed. RESULTS: For ≥F2 fibrosis, FIB-4/SWE cost $148.75/correct diagnosis while SWE cost $276.42/correct diagnosis, identifying 84% of patients correctly. For ≥F3 fibrosis, using FIB-4/SWE correctly identified 92% of diagnoses and dominated all other strategies. The ranking of strategies was unchanged when stratified by normal or abnormal ALT. For ≥F3 fibrosis, the cost/correct diagnosis was less in the normal ALT group. CONCLUSIONS: SWE based strategies were the most cost effective for diagnosing ≥F2 fibrosis. For ≥F3 fibrosis, FIB-4 followed by SWE was the most effective and least costly strategy. Further evaluation of the timing of repeating non-invasive strategies are required to enhance the cost-effective management of NAFLD.

Health care costs associated with chronic hepatitis C virus infection in Ontario, Canada: a retrospective cohort study.

BACKGROUND: High-quality estimates of health care costs are required to understand the burden of illness and to inform economic models. We estimated the costs associated with hepatitis C virus (HCV) infection from the public payer perspective in Ontario, Canada. METHODS: In this population-based retrospective cohort study, we identified patients aged 18-105 years diagnosed with chronic HCV infection in Ontario from 2003 to 2014 using linked administrative data. We allocated the time from diagnosis until death or the end of follow-up (Dec. 31, 2016) to 9 mutually exclusive health states using validated algorithms: no cirrhosis, no cirrhosis (RNA negative) (i.e., cured HCV infection), compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, both decompensated cirrhosis and hepatocellular carcinoma, liver transplantation, terminal (liver-related) and terminal (non-liver-related). We estimated direct medical costs (in 2018 Canadian dollars) per 30 days per health state and used regression models to identify predictors of the costs. RESULTS: We identified 48 239 patients with chronic hepatitis C, of whom 30 763 (63.8%) were men and 35 891 (74.4%) were aged 30-59 years at diagnosis. The mean 30-day costs were $798 (95% confidence interval [CI] $780-$816) (n = 43 568) for no cirrhosis, $661 (95% CI $630-$692) (n = 6422) for no cirrhosis (RNA negative), $1487 (95% CI $1375-$1599) (n = 4970) for compensated cirrhosis, $3659 (95% CI $3279-$4039) (n = 3151) for decompensated cirrhosis, $4238 (95% CI $3480-$4996) (n = 550) for hepatocellular carcinoma, $8753 (95% CI $7130-$10 377) (n = 485) for both decompensated cirrhosis and hepatocellular carcinoma, $4539 (95% CI $3746-$5333) (n = 372) for liver transplantation, $11 202 (95% CI $10 645-$11 760) (n = 3201) for terminal (liver-related) and $8801 (95% CI $8331-$9271) (n = 5278) for terminal (non-liver-related) health states. Comorbidity was the most significant predictor of total costs for all health states. INTERPRETATION: Our findings suggest that the financial burden of HCV infection is substantially higher than previously estimated in Canada. Our comprehensive, up-to-date cost estimates for clinically defined health states of HCV infection should be useful for future economic evaluations related to this disorder.

Trends and outcomes of peptic ulcer disease in patients with cirrhosis.

BACKGROUND: Peptic ulcer disease (PUD) is more prevalent in cirrhotic patients and it has been associated with poor outcomes. However, there are no population-based studies from the United States (U.S.) that have investigated this association. Our study aims to estimate the incidence trends, predictors, and outcomes PUD patients with underlying cirrhosis. METHODS: We analyzed Nationwide Inpatient Sample (NIS) and Healthcare Cost and Utilization Project (HCUP) data for years 2002-2014. Adult hospitalizations due to PUD were identified by previously validated ICD-9-CM codes as the primary diagnosis. Cirrhosis was also identified with presence of ICD-9-CM codes in secondary diagnosis fields. We analyzed trends and predictors of PUD in cirrhotic patients and utilized multivariate regression models to estimate the impact of cirrhosis on PUD outcomes. RESULTS: Between the years 2002-2014, there were 1,433,270 adult hospitalizations with a primary diagnosis of PUD, out of which 70,007 (4.88%) had cirrhosis as a concurrent diagnosis. There was a significant increase in the proportion of hospitalizations with a concurrent diagnosis of cirrhosis, from 3.9% in 2002 to 6.6% in 2014 (p < 0.001). In an adjusted multivariable analysis, in-hospital mortality was significantly higher in hospitalizations of PUD with cirrhosis (odd ratio [OR] 1.78; 95% confidence interval [CI] 1.63-1.97; P < 0.001), however, there was no difference in the discharge to facility (OR 1.00; 95%CI 0.94 - 1.07; P = 0.81). Moreover, length of stay (LOS) was also higher (6 days vs. 4 days, P < 0.001) among PUD with cirrhosis. Increasing age and comorbidities were associated with higher odds of in-hospital mortality among PUD patients with cirrhosis. CONCLUSION: Our study shows that there is an increased hospital burden as well as poor outcomes in terms of higher in-hospital mortality among hospitalized PUD patients with cirrhosis. Further studies are warranted for better risk stratification and improvement of outcomes.

Hepatitis C Management at Federally Qualified Health Centers during the Opioid Epidemic: A Cost-Effectiveness Study.

BACKGROUND: The opioid epidemic has been associated with an increase in hepatitis C virus (HCV) infections. Federally qualified health centers (FQHCs) have a high burden of hepatitis C disease and could serve as venues to enhance testing and treatment. METHODS: We estimated clinical outcomes and the cost-effectiveness of hepatitis C testing and treatment at US FQHCs using individual-based simulation modeling. We used individual-level data from 57 FQHCs to model 9 strategies, including permutations of HCV antibody testing modality, person initiating testing, and testing approach. Outcomes included life expectancy, quality-adjusted life-years (QALY), hepatitis C cases identified, treated and cured; and incremental cost-effectiveness ratios. RESULTS: Compared with current practice (risk-based with laboratory-based testing), routine rapid point-of-care testing initiated and performed by a counselor identified 68% more cases after (nonreflex) RNA testing in the first month of the intervention and led to a 17% reduction in cirrhosis cases and a 22% reduction in liver deaths among those with cirrhosis over a lifetime. Routine rapid testing initiated by a counselor or a clinician provided better outcomes at either lower total cost or at lower cost per QALY gained, when compared with all other strategies. Findings were most influenced by the proportion of patients informed of their anti-HCV test results. CONCLUSIONS: Routine anti-HCV testing followed by prompt RNA testing for positives is recommended at FQHCs to identify infections. If using dedicated staff or point-of-care testing is not feasible, then measures to improve immediate patient knowledge of antibody status should be considered.

Weekend admissions with ascites are associated with delayed paracentesis: A nationwide analysis of the 'weekend effect'.

INTRODUCTION AND OBJECTIVES: Weekend admissions has previously been associated with worse outcomes in conditions requiring specialists. Our study aimed to determine in-hospital outcomes in patients with ascites admitted over the weekends versus weekdays. Time to paracentesis from admission was studied as current guidelines recommend paracentesis within 24h for all patients admitted with worsening ascites or signs and symptoms of sepsis/hepatic encephalopathy (HE). PATIENTS: We analyzed 70 million discharges from the 2005-2014 National Inpatient Sample to include all adult patients admitted non-electively for ascites, spontaneous bacterial peritonitis (SBP), and HE with ascites with cirrhosis as a secondary diagnosis. The outcomes were in-hospital mortality, complication rates, and resource utilization. Odds ratios (OR) and means were adjusted for confounders using multivariate regression analysis models. RESULTS: Out of the total 195,083 ascites/SBP/HE-related hospitalizations, 47,383 (24.2%) occurred on weekends. Weekend group had a higher number of patients on Medicare and had higher comorbidity burden. There was no difference in mortality rate, total complication rates, length of stay or total hospitalization charges between the patients admitted on the weekend or weekdays. However, patients admitted over the weekends were less likely to undergo paracentesis (OR 0.89) and paracentesis within 24h of admission (OR 0.71). The mean time to paracentesis was 2.96 days for weekend admissions vs. 2.73 days for weekday admissions. CONCLUSIONS: We observed a statistically significant "weekend effect" in the duration to undergo paracentesis in patients with ascites/SBP/HE-related hospitalizations. However, it did not affect the patient's length of stay, hospitalization charges, and in-hospital mortality.

Cost-Effectiveness of Rifaximin Treatment in Patients with Hepatic Encephalopathy.

BACKGROUND: Hepatic encephalopathy (HE) is a complication of cirrhosis of the liver causing neuropsychiatric abnormalities. Clinical manifestations of overt HE result in increased health care resource utilization and effects on patient quality of life. While lactulose has historically been the mainstay of treatment for acute HE and maintenance of remission, there is an unmet need for additional therapeutic options with a favorable adverse event profile. Compared with lactulose alone, rifaximin has demonstrated proven efficacy in complete reversal of HE and reduction in the incidence of HE recurrence, mortality, and hospitalizations. Evidence suggests the benefit of long-term prophylactic therapy with rifaximin; however, there is a need to assess the economic impact of rifaximin treatment in patients with HE. OBJECTIVE: To assess the incremental cost-effectiveness of rifaximin ± lactulose versus lactulose monotherapy in patients with overt HE. METHODS: A Markov model was developed in Excel with 4 health states (remission, overt HE, liver transplantation, and death) to predict costs and outcomes of patients with HE after initiation of maintenance therapy with rifaximin ± lactulose to avoid recurrent HE episodes. Cost-effectiveness of rifaximin was evaluated through estimation of incremental cost per quality-adjusted life-year (QALY) or life-year (LY) gained. Analyses were conducted over a lifetime horizon. One-way deterministic and probabilistic sensitivity analyses were conducted to assess uncertainty in results. RESULTS: The rifaximin ± lactulose regimen provided added health benefits despite an additional cost versus lactulose monotherapy. Model results showed an incremental benefit of $29,161 per QALY gained and $27,762 per LY gained with rifaximin ± lactulose versus lactulose monotherapy. Probabilistic sensitivity analyses demonstrated that the rifaximin ± lactulose regimen was cost-effective ~99% of the time at a threshold of $50,000 per QALY/LY gained, which falls within the commonly accepted threshold for incremental cost-effectiveness. CONCLUSIONS: The clinical benefit of rifaximin, combined with an acceptable economic profile, demonstrates the advantages of rifaximin maintenance therapy as an important option to consider for patients at risk of recurrent HE. DISCLOSURES: This analysis was funded by Salix Pharmaceuticals, a division of Bausch Health US. Salix and Xcenda collaborated on the methods, and Salix, Xcenda, Jesudian, and Ahmad collaborated on the writing of the manuscript and interpretation of results. Bozkaya and Migliaccio-Walle are employees of Xcenda. Ahmad reports speaker fees from Salix Pharmaceuticals, unrelated to this study. Jesudian reports consulting and speaker fees from Salix Pharmaceuticals, unrelated to this study. The results from this model were presented at AASLD: The Liver Meeting 2014; November 7-11; Boston, MA.

Healthcare resource utilization and costs of nonalcoholic steatohepatitis patients with advanced liver disease in Italy.

BACKGROUND AND AIMS: Nonalcoholic steatohepatitis (NASH) may progress to advanced liver disease (AdvLD). This study characterized comorbidities, healthcare resource utilization (HCRU) and associated costs among hospitalized patients with AdvLD due to NASH in Italy. METHODS AND RESULTS: Adult nonalcoholic fatty liver disease (NAFLD)/NASH patients from 2011 to 2017 were identified from administrative databases of Italian local health units using ICD-9-CM codes. Development of compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), or liver transplant (LT) was identified using first diagnosis date for each severity cohort (index-date). Patients progressing to multiple disease stages were included in >1 cohort. Patients were followed from index-date until the earliest of disease progression, end of coverage, death, or end of study. Within each cohort, per member per month values were annualized to calculate all-cause HCRU or costs(€) in 2017. Of the 9,729 hospitalized NAFLD/NASH patients identified, 97% were without AdvLD, 1.3% had CC, 3.1% DCC, 0.8% HCC, 0.1% LT. Comorbidity burden was high across all cohorts. Mean annual number of inpatient services was greater in patients with AdvLD than without AdvLD. Similar trends were observed in outpatient visits and pharmacy fills. Mean total annual costs increased with disease severity, driven primarily by inpatient services costs. CONCLUSION: NAFLD/NASH patients in Italy have high comorbidity burden. AdvLD patients had significantly higher costs. The higher prevalence of DCC compared to CC in this population may suggest challenges of effectively screening and identifying NAFLD/NASH patients. Early identification and effective management are needed to reduce risk of disease progression and subsequent HCRU and costs.

Skeletal muscle loss phenotype in cirrhosis: A nationwide analysis of hospitalized patients.

BACKGROUND & AIMS: There are very limited data on the healthcare burden of muscle loss, the most frequent complication in hospitalized cirrhotics. We determined the healthcare impact of a muscle loss phenotype in hospitalized cirrhotics. METHODS: The Nationwide Inpatient Sample (NIS) database (years 2010-2014) was analyzed. Search terms included cirrhosis and its complications, and an expanded definition of a muscle loss phenotype that included all conditions associated with muscle loss. In-hospital mortality, length of stay (LOS), post-discharge disposition, co-morbidities and cost during admission were analyzed. Univariate and multivariate analyses were performed to identify associations between a muscle loss phenotype and outcomes. Impact of muscle loss in cirrhotics was compared to that in a random sample (2%) of general medical inpatients. RESULTS: A total of 162,694 hospitalizations for cirrhosis were reported, of which 18,261 (11.2%) included secondary diagnosis codes for a muscle loss phenotype. A diagnosis of muscle loss was associated with a significantly (p < 0.001 for all) higher mortality (19.3% vs 8.2%), LOS (14.2 ± 15.8 vs. 4.6 ± 6.9 days), and median hospital charge per admission ($21,400 vs. $8573) and a lower likelihood of discharge to home (30.1% vs. 60.2%). All evaluated outcomes were more severe in cirrhotics than general medical patients (n = 534,687). Multivariate regression analysis showed that a diagnosis of muscle loss independently increased mortality by 130%, LOS by 80% and direct cost of care by 119% (p < 0.001 for all). Alcohol use, female gender, malignancies and other organ dysfunction were independently associated with muscle loss. CONCLUSIONS: Muscle loss contributed to higher mortality, LOS, and direct healthcare costs in hospitalized cirrhotics.

Economic Evaluation of Hepatitis C Treatment Extension to Acute Infection and Early-Stage Fibrosis Among Patients Who Inject Drugs in Developing Countries: A Case of China.

We aimed to assess the cost-effectiveness of (1) treating acute hepatitis C virus (HCV) vs deferring treatment until the chronic phase and (2) treating all chronic patients vs only those with advanced fibrosis; among Chinese genotype 1b treatment-naïve patients who injected drugs (PWID), using a combination Daclatasvir (DCV) plus Asunaprevir (ASV) regimen and a Peg-interferon (PegIFN)-based regimen, respectively. A decision-analytical model including the risk of HCV reinfection simulated lifetime costs and quality-adjusted life-years (QALYs) of three treatment timings, under the DCV+ASV and PegIFN regimen, respectively: Treating acute infection ("Treat at acute"), treating chronic patients of all fibrosis stages ("Treat at F0 (no fibrosis)"), treating only advanced-stage fibrosis patients ("Treat at F3 (numerous septa without cirrhosis)"). Incremental cost-effectiveness ratios (ICERs) were used to compare scenarios. "Treat at acute" compared with "Treat at F0" was cost-saving (cost: DCV+ASV regimen-US$14,486.975 vs US$16,224.250; PegIFN-based regimen-US$19,734.794 vs US$22,101.584) and more effective (QALY: DCV+ASV regimen-14.573 vs 14.566; PegIFN-based regimen-14.148 vs 14.116). Compared with "Treat at F3"; "Treat at F0" exhibited an ICER of US$3780.20/QALY and US$15,145.98/QALY under the DCV+ASV regimen and PegIFN-based regimen; respectively. Treatment of acute HCV infection was highly cost-effective and cost-saving compared with deferring treatment to the chronic stage; for both DCV+ASV and PegIFN-based regimens. Early treatment for chronic patients with DCV+ASV regimen was highly cost-effective.