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.

Economic Implications of Hepatocellular Carcinoma Surveillance and Treatment: A Guide for Clinicians.

The incidence of hepatocellular carcinoma (HCC) is increasing worldwide, with significant morbidity and associated costs. Treatment allocation depends on the stage of diagnosis; however, resource utilization can be significant across all stages. We aimed to summarize the available data on the cost effectiveness of surveillance of and treatments for HCC in the context of current treatment guidelines. We performed a focused review of studies investigating the economic burden and cost effectiveness of HCC surveillance treatment modalities published between January 2000 and January 2019. The overall economic burden of HCC is increasing in the USA and in several countries worldwide due to its rising incidence and the proliferation of therapies. Liver transplantation is a cost-effective strategy for early-stage HCC treatment in selected patients. In settings where liver transplantation is not available or in patients awaiting transplant, ablative or locoregional therapies are cost effective with increases in quality-adjusted life-years. First-line therapy with sorafenib for advanced stage HCC is cost effective in the treatment of compensated cirrhosis. The cost effectiveness of recently approved systemic therapies for advanced HCC require further investigation. Existing studies have shown that guideline-recommended surveillance techniques and several available therapies for the treatment of HCC are cost effective; however, there are limitations in the literature, including reliance on suboptimal modeling with incomplete/simplified model structure or inadequate inputs. With increasing therapeutic options in patients with HCC, understanding their relative value is critical in designing HCC treatment algorithms.

Economic Consequences of Investing in Anti-HCV Antiviral Treatment from the Italian NHS Perspective: A Real-World-Based Analysis of PITER Data.

OBJECTIVE: We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy. METHODS: A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulative costs saved to recover the Italian NHS investment in DAA treatment. Three different PITER enrolment periods, which covered the full DAA access evolution in Italy, were considered. RESULTS: The disease stages of 2657 patients who consecutively underwent DAA therapy from January 2015 to December 2017 at 30 PITER clinical centres were standardized for 1000 patients. The investment in DAAs was considered to equal €25 million, €15 million, and €9 million in 2015, 2016, and 2017, respectively. For patients treated in 2015, the BPT was not achieved, because of the disease severity of the treated patients and high DAA prices. For 2016 and 2017, the estimated BPTs were 6.6 and 6.2 years, respectively. The total cost savings after 20 years were €50.13 and €55.50 million for 1000 patients treated in 2016 and 2017, respectively. CONCLUSIONS: This study may be a useful tool for public decision makers to understand how HCV clinical and epidemiological profiles influence the economic burden of HCV.

[Current drug treatment of hepatitis C : Useful therapy algorithms taking into consideration economical aspects]. / Aktuelle Arzneimitteltherapie der Hepatitis C : Sinnvolle Therapiealgorithmen unter Berücksichtigung ökonomischer Aspekte.

Treatment of chronic hepatitis C (HCV) has changed dramatically since the approval of the direct-acting antivirals (DAA). Depending on the HCV genotype and the stage of liver disease, sustained HCV clearance can be achieved in more than 95% of patients with a treatment duration of 8-12 weeks in most of the cases. The selection and combination of the drugs depends on previous antivirals therapies, the stage of liver fibrosis, HCV genotype and subtype, viral load at baseline, and renal function. Nowadays, potent antiviral therapy with minimal side effects can be offered to almost every patient. In the real-world setting, a high quality of HCV therapy considering economic aspects has been documented in the German Hepatitis C Registry. A reduction of clinical complications of chronic liver disease by clearance of HCV has already been documented.

[Economic aspects of inpatient treatment for decompensated liver cirrhosis: a prospective study employing an evidence-based clinical pathway]. / Gesundheitsökonomische Aspekte der stationären Behandlung von Patienten mit dekompensierter Leberzirrhose: eine prospektive Studie unter Nutzung eines evidenzbasierten Behandlungspfads.

The introduction of the G-DRG reimbursement system has greatly increased the pressure to provide cost effective treatment in German hospitals. Reimbursement based on diagnosis-related groups, which requires stratification of costs incurred is still not sufficiently discriminating the disease severity and severity in relation to the intensive costs in gastroenterology. In a combined retrospective and prospective study at a tertial referral centre we investigated whether this also applies for decompensated liver cirrhosis. In 2006, 64 retrospective cases (age 57 ± 12.9; ♂ 69.2 %, ♀ 29.8 %) with decompensated liver cirrhosis (ICD code K76.4) were evaluated for their length of hospitalisation, reimbursement as well as Child and MELD scores. In 2008, 74 cases with decompensated liver cirrhosis were treated in a prospective study according to a standardised and evidence-based clinical pathway (age 57 ± 12.2; 73 % ♂, ♀ 27 %). Besides a trend in the reduction of length of hospital stay (retrospective: 13.6 ± 8.6, prospective 13.0 ± 7.2, p = 0.85) overall revenues from patients treated according to a evidence-based clinical pathway were lower than the calculated costs from the InEK matrix. Costs of medication as a percentage of reimbursement amount increased with increasing severity. In both years we could demonstrate an inverse correlation between daily reimbursement and disease severity which precluded cost coverage. For the cost-covering hospital treatment of patients with decompensated liver cirrhosis an adjustment of the DRG based on clinical severity scores such as Child-Pugh or MELD is warranted, if evidence-based treatment standards are to be kept.

The cost-effectiveness of alternative strategies against HBV in Italy.

INTRODUCTION: Nowadays, guidelines for the management of HBV infection in Italy, recommend using vaccines but the screening test among non-vaccinated people is useful to detect people that have a clear presence of the virus without symptoms of the disease. Thanks to the screening test, people infected with HBV are administered traditional therapy in order to stop the progression to cirrhosis, liver failure and hepatocellular carcinoma (HCC). These diseases cause the decrease of Qol and cause a high consumption of resources for the health system. The aim of this study is to evaluate the cost-effectiveness of a strategy (test strategy) involving the administration of the screening test to patients at risk and the treatment of the infected according to the protocol therapy. This programme is compared with a strategy (no test strategy) which does not include a screening and treats patients affected by cirrhosis or HCC. METHODS: We created a Markov model following the natural history of the disease and considering the antigen HBeAg to evaluate the cost effectiveness of the test strategy. The analysis was carried out considering a third-party payer perspective. The time horizon considered was 40 cycles of one year. Patients who resulted positive to the test were administered either interferon treatment; or lamivudine or adefovir or entecavir or tenofovir, consistently with the Italian guidelines. Treatments were administered to patients included in the no-test arm after cirrhosis symptoms or HCC. RESULTS: The results of the base case analysis show that patients following the test strategy compared with patients of the no-test approach cost €17,179/QALY. The Monte Carlo simulation based on a probabilistic sensitivity analysis points out that in 95% of the scenarios assumed, the cost per QALY would be under a hypothetical threshold of €40,000 which is the amount that international guidelines for decision makers are likely to consider sustainable for a health system. In conclusion, anti-hbv test to all high-risk categories should be highly recommended.

Critical issues in the treatment of hepatitis C virus infection in methadone maintenance patients.

AIMS: Hepatitis C virus (HCV) infection is a common chronic complication of injection drug use. Methadone maintenance programs contain large numbers of patients infected with HCV. This paper reviews HCV infection with emphasis on the medical care of HCV-infected, or HCV and human immunodeficiency virus co-infected, patients on methadone or buprenorphine maintenance. METHODS: Literature searches using PubMed, PsycINFO and SocINDEX were used to identify papers from 1990-present on antiviral therapy for HCV in methadone maintenance patients and on liver transplantation in methadone maintenance patients. RESULTS: Injection drug use is the most significant risk factor for HCV infection in most western countries. The prevalence of HCV antibody is high in injection drug users (53-96%) and in patients enrolled in methadone maintenance programs (67-96%). Studies of antiviral therapy for HCV in methadone maintenance patients show rates of sustained virological response (SVR), defined as negative HCV-RNA 24 weeks after the end of treatment, of 28-94%. In studies with contrast groups, no significant differences in SVR between methadone and contrast groups were found. Excellent completion rates of antiviral therapy (72-100%) were found in five of six studies. There are many barriers to methadone maintenance patients' receiving antiviral therapy, and research on overcoming barriers is discussed. Liver transplantation has been successful in methadone maintenance patients but has not been utilized widely. CONCLUSION: High quality medical care for all aspects of HCV infection can be provided to methadone maintenance patients. The literature supports the effectiveness of such services, but the reality is that most patients do not receive them.

Treatment alternatives for hepatitis B cirrhosis: a cost-effectiveness analysis.

BACKGROUND: Hepatitis B virus (HBV) patients with cirrhosis are at risk for developing costly, morbid, or mortal events, and therefore need highly effective therapies. Lamivudine is effective but is limited by viral resistance. In contrast, adefovir and entecavir have lower viral resistance, but are more expensive. The most cost-effective approach is uncertain. METHODS: We evaluated the cost-effectiveness of six strategies in HBV cirrhosis: (1) No HBV treatment ("do nothing"), (2) lamivudine monotherapy, (3) adefovir monotherapy, (4) lamivudine with crossover to adefovir on resistance ("adefovir salvage"), (5) entecavir monotherapy, or (6) lamivudine with crossover to entecavir on resistance ("entecavir salvage"). The primary outcome was the incremental cost per quality-adjusted life-year (QALY) gained. RESULTS: The "do nothing" strategy was least effective yet least expensive. Compared with "do nothing," using adefovir cost an incremental US dollars 19,731. Entecavir was more effective yet more expensive than adefovir, and cost an incremental US dollars 25,626 per QALY gained versus adefovir. Selecting between entecavir versus adefovir was highly dependent on the third-party payer's "willingess-to-pay" (e.g., 45% and 60% of patients fall within budget if willing-to-pay US dollars 10K and US dollars 50K per QALY gained for entecavir, respectively). Both lamivudine monotherapy and the "salvage" strategies were not cost-effective. However, between the two salvage strategies, "adefovir salvage" was more effective and less expensive than "entecavir salvage." CONCLUSION: Both entecavir and adefovir are cost-effective in patients with HBV cirrhosis. Choosing between adefovir and entecavir is highly dependent on available budgets. In patients with HBV cirrhosis with previous lamivudine resistance, "adefovir salvage" appears more effective and less expensive than "entecavir salvage."

[Study on the cost-effectiveness, benefit and utility analysis on the infant inoculation hepatitis B vaccine in Shanghai].

OBJECTIVE: To study the cost-effectiveness, benefit and utility of infant hepatitis B vaccination in Shanghai from 1992 to 2001. METHODS: To calculate the cost of hepatitis B vaccination by cost analysis method. Both the numbers of persons with HBsAg positive and patient with hepatitis B, cirrhosis and liver cancer decreased as the index of direct effect. To study the sick-time and the cost of treating hepatitis B, cirrhosis and liver cancer patients, a face to face questionnaire was used and quasi method was adopted to understand the effect of cure and the course of hepatitis B. The cost benefit analysis method was also used to calculate the cost benefit of HBV vaccine. The disability adjusted life years (DALY) was regarded as an index of utility to measure the disease burden. RESULTS: Input of 501,129.49 Yuan might have the result of reducing one liver cancer patient, ten cirrhosis patients, one hundred chronic hepatitis B patients and one thousand HBsAg positive people. The cost of hepatitis B vaccination was 0.24 hundred million Yuan during the past ten years in Shanghai, which had obtained the total benefit value of 41.22 hundred million Yuan, with a cost benefit ratio of 1:172 Yuan. It was estimated that the total disease burden of hepatitis B, cirrhosis and liver cancer patients was 59,762.55 DALY in order to reduce one DALY loss cost of 402.50 Yuan. CONCLUSION: HBV vaccine inoculation in infants seemed to be a low-cost input and high-effect output strategy.