Telemedicine, time to change the paradigm of hepatitis C management: improve access and reduce costs In reference to: Chronic viral hepatitis C micro-elimination program using telemedicine. The Mexican experience, by Pérez Hernández et al.

Hepatitis C (HCV) management has dramatically changed with the advent of direct-acting antivirals. Their high efficacy and safety are changing the paradigm of detection and treatment of patients with an active HCV infection. Following the latest guidelines, the path to elimination of hepatitis C will be achieved by simplifying management.

Disease burden and economic impact of diagnosed non-alcoholic steatohepatitis in five European countries in 2018: A cost-of-illness analysis.

BACKGROUND AND AIMS: Non-alcoholic steatohepatitis (NASH) is a chronic disease that can progress to end-stage liver disease (ESLD). A large proportion of early-stage NASH patients remain undiagnosed compared to those with advanced fibrosis, who are more likely to receive disease management interventions. This study estimated the disease burden and economic impact of diagnosed NASH in the adult population of France, Germany, Italy, Spain and the United Kingdom in 2018. METHODS: The socioeconomic burden of diagnosed NASH was estimated using cost-of-illness methodology applying a prevalence approach to estimate the number of adults with NASH and the attributable economic and wellbeing costs. Given undiagnosed patients do not incur costs in the study, the probability of diagnosis is central to cost estimation. The analysis was based on a literature review, databases and consultation with clinical experts, economists and patient groups. RESULTS: The proportion of adult NASH patients with a diagnosis ranged from 11.9% to 12.7% across countries, which increased to 38.8%-39.1% for advanced fibrosis (F3-F4 compensated cirrhosis). Total economic costs were €8548-19 546M. Of these, health system costs were €619-1292M. Total wellbeing costs were €41 536-90 379M. The majority of the undiagnosed population (87.3%-88.2% of total prevalence) was found to have early-stage NASH, which, left untreated, may progress to more resource consuming ESLD over time. CONCLUSIONS: This study found that the majority of economic and wellbeing costs of NASH are experienced in late disease stages. Earlier diagnosis and care of NASH patients could reduce future healthcare costs.

Biochemical assessment of metabolic associated fatty liver disease.

Metabolic-associated fatty liver disease (MAFLD) is defined as fat accumulation in the liver in the presence of metabolic alterations. This disorder is generally asymptomatic and may progress to severe liver disease, which are linked to inflammation and/or fibrosis. MAFLD has a high prevalence (26%) and therefore a considerable number of patients are at high risk of having advanced liver disease. This document provides an overview of the most relevant serological markers in the characterization and diagnosis of MAFLD. An example is provided of a routine diagnostic algorithm that incorporates serological testing. A range of useful serological scores are currently available for the management of MAFLD patients, especially for the stratification of patients at risk of fibrosis. A large proportion of the population is at risk of developing severe liver disease. The integration of non-invasive serological markers in the stratification of patients at risk for liver fibrosis may contribute to improve the control and management of MAFLD patients.

Telemedicine efficiently improves access to hepatitis C management to achieve HCV elimination in the penitentiary setting.

INTRODUCTION: Linkage to care for hepatitis C includes a new tool: teleconsultation. Micro-elimination in prison is a recommendation and is feasible. An economic evaluation of telemedicine for hepatitis C virus (HCV) treatment in prisons has not yet been performed. This study aimed to provide a cost-minimization analysis comparing two strategies of HCV treatment in a prison: telemedicine clinical practice (TCP) and the usual clinical practice (UCP). METHODS: An observational cost-minimization study was carried out on a cohort of inmates who received anti-HCV treatment in El Dueso prison (May 2016-November 2017). A decision tree was constructed, incorporating different clinical profiles according to the severity of the disease, the results of diagnostic tests, and treatment outcomes as well as the costs of each profile. Satisfaction with telemedicine was evaluated through an 11-question questionnaire with a 5-point Likert scale. RESULTS: Seventy-five inmates were treated and underwent TCP with a follow-up of one year. The average cost per patient with the TCP strategy was €1,172 (€1,151 direct costs). Had UCP been carried out, the cost would have been €1,687 (€1,630 direct). Telemedicine consultation practice produced savings of €516 (30.6%) per patient, with total savings of €38,677. The transfer costs from prison to hospital represented the most important saving item, accounting for 99.3% of the TCP-related savings. The questionnaire revealed high levels of satisfaction with TCP, with a median score of 5 in each question. Sustained virological response rates were 94.7% after the first treatment and 100% after retreatment of the four relapses. CONCLUSION: Telemedicine consultation practice is a more efficient strategy than UCP, mainly due to the reduction of transfer costs while preserving effectiveness and user satisfaction.

Overall clinical and economic impact of non-alcoholic fatty liver disease.

OBJECTIVES: to establish the clinical and economic consequences (resource utilization and healthcare costs) of non-alcoholic fatty liver in the setting of the usual clinical practice in Spain. PATIENTS AND METHODS: an observational, retrospective study was performed based on a review of the medical records of adult patients ≥ 18 years of age who sought medical care from 2017 to 2018. Patients were categorized into two groups according to fibrosis stage (estimation method: FIB-4): a) F0-F2; and b) F3-F4 (advanced fibrosis). Follow-up lasted one year. Primary endpoints included comorbidity, concomitant medication, resource utilization and costs. Results were analyzed using a multivariate approach with p < 0.05. RESULTS: a total of 8,151 patients were recruited with a mean age of 61.1 years and 51.5 % were male. By group: a) mild fibrosis n = 7,127, 87.4 %; and b) advanced fibrosis n = 1,024, 12.6 % (6.8 % with liver cirrhosis). The most common comorbidities included 63 % dyslipidemia, 52 % obesity, 52 % hypertension and 35 % diabetes. The average number of drugs used was 2.1 per patient. Patients with advanced fibrosis (F3-F4) had a higher average number of concomitant medications (2.5 vs 2.1; p < 0.001) and a higher AST/ALT ratio (1.1 vs 0.8; p < 0.001). The average cost (patient-year) for subjects with advanced fibrosis, corrected for covariates, was higher (€1,812 vs €1,128, p < 0.001). Age, morbidity, concomitant medication, fibrosis stage and total costs were higher in patients with diabetes. CONCLUSIONS: patients with advanced fibrosis were associated with more comorbidity and concomitant medications, which resulted in higher healthcare costs for the National Health System.

Principles for implementing a population screening strategy for hepatitis C in Spain.

BACKGROUND: hepatitis C, besides health impairment, results in significant loss of productivity and diminished quality of life, and noticeably contributes to health expenditure increases. Because of all this, the Spanish Ministry of Health (Ministerio de Sanidad, Consumo y Bienestar Social - MSCBS) implemented in 2015 a strategic plan for managing hepatitis C (Plan Estratégico para el Abordaje de la Hepatitis C - PEAHC) within the National Health System. However, the PEAHC includes no screening plan. The MSCBS developed a framework document on population screening (Documento Marco sobre Cribado Poblacional) that defines the criteria a disease must meet in order to consider implementing a screening program. Specifically, it defines 4 criteria related to the health issue, 4 related to the screening test, and 3 criteria dealing with diagnosis confirmation and treatment. OBJECTIVE: to identify whether there is scientific evidence to support hepatitis C meeting the criteria to be considered a disease qualifying for a population screening strategy in Spain. METHODS: a literature search for scientific evidence concerning each required criterion for implementing a population screening plan for hepatitis C in Spain. RESULTS: sufficient scientific evidence was found to support hepatitis C meeting the criteria required by the MSCBS for the implementation of a population screening program. CONCLUSIONS: according to the available scientific evidence, hepatitis C in Spain meets the required criteria to qualify for consideration of population screening plan.

Epidemiology of hepatitis C virus infection in a country with universal access to direct-acting antiviral agents: Data for designing a cost-effective elimination policy in Spain.

Accurate HCV prevalence estimates are necessary for guiding elimination policies. Our aim was to determine the HCV prevalence and assess the cost-effectiveness of a screen-and-treat strategy in the Spanish population. A population-based, cross-sectional study (PREVHEP-ETHON Cohort, Epidemiological sTudy of Hepatic infectiONs; NCT02749864) was performed from July 2015-April 2017. Participants from three Spanish regions were selected using two-stage conglomerate sampling, and stratified by age, with randomized subject selection. Anthropometric and demographic data were collected, and blood samples were taken to detect anti-HCV antibodies/quantify HCV RNA. The cost-effectiveness of the screening strategies and treatment were analysed using a Markov model. Among 12 246 participants aged 20-74 (58.4% females), the overall anti-HCV prevalence was 1.2% (95% CI 1.0-1.4), whereas the detectable HCV-RNA prevalence was 0.3% (0.2-0.4). Infection rates were highest in subjects aged 50-74 years [anti-HCV 1.6% (1.3-1.9), HCV RNA 0.4% (0.3-0.6]. Among the 147 anti-HCV + subjects, 38 (25.9%) had active infections while 109 (74.1%) had been cleared of infection; 44 (40.4%) had cleared after antiviral treatment, whereas 65 (59.6%) had cleared spontaneously. Overall, 59.8% of the anti-HCV + participants were aware of their serological status. Considering a cost of treatment of €7000/patient, implementing screening programmes is cost-effective across all age cohorts, particularly in patients aged 50-54 (negative incremental cost-effectiveness ratio which indicates a cost-saving strategy). The current HCV burden is lower than previously estimated, with approximately 25% of anti-HCV + individuals having an active infection. A strategy of screening and treatment at current treatment prices in Spain is cost-effective across all age cohorts.

Improved Health Outcomes from Hepatitis C Treatment Scale-Up in Spain's Prisons: A Cost-Effectiveness Study.

Hepatitis C virus (HCV) is 15 times more prevalent among persons in Spain's prisons than in the community. Recently, Spain initiated a pilot program, JAILFREE-C, to treat HCV in prisons using direct-acting antivirals (DAAs). Our aim was to identify a cost-effective strategy to scale-up HCV treatment in all prisons. Using a validated agent-based model, we simulated the HCV landscape in Spain's prisons considering disease transmission, screening, treatment, and prison-community dynamics. Costs and disease outcomes under status quo were compared with strategies to scale-up treatment in prisons considering prioritization (HCV fibrosis stage vs. HCV prevalence of prisons), treatment capacity (2,000/year vs. unlimited) and treatment initiation based on sentence lengths (>6 months vs. any). Scaling-up treatment by treating all incarcerated persons irrespective of their sentence length provided maximum health benefits-preventing 10,200 new cases of HCV, and 8,300 HCV-related deaths between 2019-2050; 90% deaths prevented would have occurred in the community. Compared with status quo, this strategy increased quality-adjusted life year (QALYs) by 69,700 and costs by €670 million, yielding an incremental cost-effectiveness ratio of €9,600/QALY. Scaling-up HCV treatment with DAAs for the entire Spanish prison population, irrespective of sentence length, is cost-effective and would reduce HCV burden.

Shadows in the current management of hepatocellular carcinoma in Spain - An embarrassing truth.

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related deaths worldwide. Up to 80% of patients with HCC have concomitant cirrhosis as a result of hepatitis B or C virus, alcohol abuse, or non-alcoholic steatohepatitis.

The efficiency of several one-step testing strategies for the diagnosis of hepatitis C.

BACKGROUND: implementing one-step strategies for hepatitis C diagnosis would help shorten the time to treatment access. Thus avoiding disease progression and complications, while facilitating hepatitis C virus (HCV) elimination. OBJECTIVE: to assess the validity and certainty of potential one-step strategies for the diagnosis of HCV infection and their associated cost and efficiency. METHODS: the study design is an economic appraisal of efficiency (cost/efficacy) using decision trees and deterministic sensitivity analysis. The analysis was performed from the payer perspective (Spanish National Health System), which exclusively considers the direct costs. Only the differential costs (diagnostic testing costs) were taken into account and the study was set in Spain. The efficacy of a diagnostic strategy was defined as the percentage of patients with an active HCV infection who received a positive diagnosis and the efficiency was defined as the cost per patient with a correctly diagnosed and active infection. RESULTS: the one-step strategies evaluated for the diagnosis of HCV had an acceptable validity and certainty due to the high sensitivity and specificity of the considered tests. The Ab-Ag strategy was the most efficient, followed by Ab-Ag-VL and Ab-VL. Ab-Ag was the most efficient due to the lower cost per patient tested, although the efficacy was lower than the Ab-VL efficacy. CONCLUSION: the study findings may help to establish more appropriate one-step diagnostic approaches whilst considering the efficacy and efficiency.

Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are increasingly a cause of cirrhosis and hepatocellular carcinoma globally. This burden is expected to increase as epidemics of obesity, diabetes and metabolic syndrome continue to grow. The goal of this analysis was to use a Markov model to forecast NAFLD disease burden using currently available data. METHODS: A model was used to estimate NAFLD and NASH disease progression in eight countries based on data for adult prevalence of obesity and type 2 diabetes mellitus (DM). Published estimates and expert consensus were used to build and validate the model projections. RESULTS: If obesity and DM level off in the future, we project a modest growth in total NAFLD cases (0-30%), between 2016-2030, with the highest growth in China as a result of urbanization and the lowest growth in Japan as a result of a shrinking population. However, at the same time, NASH prevalence will increase 15-56%, while liver mortality and advanced liver disease will more than double as a result of an aging/increasing population. CONCLUSIONS: NAFLD and NASH represent a large and growing public health problem and efforts to understand this epidemic and to mitigate the disease burden are needed. If obesity and DM continue to increase at current and historical rates, both NAFLD and NASH prevalence are expected to increase. Since both are reversible, public health campaigns to increase awareness and diagnosis, and to promote diet and exercise can help manage the growth in future disease burden. LAY SUMMARY: Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis can lead to advanced liver disease. Both conditions are becoming increasingly prevalent as the epidemics of obesity and diabetes continue to increase. A mathematical model was built to understand how the disease burden associated with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis will change over time. Results suggest increasing cases of advanced liver disease and liver-related mortality in the coming years.

Cost-effectiveness of a hepatitis B virus screening strategy to prevent reactivation in patients with hematologic neoplasms.

INTRODUCTION: The effectiveness of a screening strategy for the detection of a hepatitis B virus (HBV) infection followed by prophylaxis in order to prevent HBV reactivation was assessed in patients with hematologic neoplasms. MATERIAL AND METHODS: A decision tree was developed to compare the cost and effectiveness (prevented reactivations) over an 18 month period of a screening strategy prior to chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) with a non-screening approach. HBsAg+ (hepatitis B surface antigen) and/or anti-HBc+ (antibodies to hepatitis B core antigen) and HBV-DNA+ patients received oral antiviral prophylaxis with tenofovir disoproxil (245 mg once daily) from chemotherapy baseline until one year after chemotherapy completion. Non-screened patients received tenofovir in case of a reactivation. Model probabilities were obtained from the literature. The total cost (€, 2015) included: antiviral prophylaxis, R-CHOP, screening tests (HBsAg, anti-HBc, HBV-DNA) and liver function tests. Drug therapy costs were estimated using ex-factory prices with mandatory deductions. The incremental cost-effectiveness ratio (ICER) was calculated in order to assess the cost-effectiveness of this intervention in terms of cost per reactivation averted versus no screening. RESULTS: In a hypothetical cohort of 1,000 patients, screening prevented 7.36 reactivations when compared to the non-screening approach (14.9 versus 22.3). Total cost/patient (including €8,282 for R-CHOP) was €8,584 for the screening strategy and €8,449 for the non-screening approach. The ICER for screening versus non-screening was €18,376/prevented reactivation. CONCLUSION: HBV screening followed by oral antiviral prophylaxis yielded more health benefits than non-screening, reducing HBV reactivation in patients with hematologic neoplasms on chemotherapy.

Pharmacoeconomic analysis of the treatment of chronic hepatitis C with peginterferon alfa-2a or peginterferon alfa-2b plus ribavirin in Spain.

BACKGROUND: An independent meta-analysis of randomized comparative trials of peginterferons alfa-2a and alfa-2b, both combined with ribavirin, analyzed the probability of achieving a sustained virological response (SVR). OBJECTIVE: To estimate the long-term cost-effectiveness of treatment of patients with chronic hepatitis C with peginterferon alfa-2a (180µg/week) plus ribavirin (800-1200mg/day) vs. alfa-2b (1.5µg/kg/week) plus ribavirin (800-1400mg/day), from the perspective of the Spanish National Health System. METHODS: A Markov model was developed with 7 health states to simulate lifetime disease progression. SVR was calculated from the meta-analysis data. Transition probabilities and health state utilities were obtained from published literature. Direct healthcare costs were obtained from the drug catalog, while costs of disease-related complications were obtained from published studies and healthcare cost database. Costs were expressed in 2010€. The annual discount rate applied was 3.5% for both costs and benefits. RESULTS: SVR rate for treatment with alfa-2a was higher than with alfa-2b; the differences were 6.0%, 7.6% and 8.7% for all genotypes, genotypes 1/4 and genotypes 2/3, respectively. Each patient would gain 0.469, 0.600 and 0.685 life-years and 0.155, 0.198 and 0.227 quality-adjusted life-years with alfa-2a vs. alfa-2b, for the respective genotypes. The cost saving per patient treated with alfa-2a would be €705, €672 and €1900, for all genotypes and for genotypes 1/4 and 2/3, respectively, alfa-2a being dominant. CONCLUSIONS: According to the present model, treatment of patients with chronic hepatitis C with peginterferon alfa-2a is cost-effective compared with peginterferon alfa-2b, both combined with ribavirin.

[Adefovir dipivoxil compassionate use program in Spain: efficacy and resistance analysis]. / Programa de uso compasivo con adefovir dipivoxil en España: valoración de su eficacia y estudio de las resistencias.

BACKGROUND AND OBJECTIVE: The extended treatment with lamivudine in patients with chronic hepatitis B is associated with the emergence of resistances. Patients with resistance to lamivudine show a loss of biochemical and virological responses and a higher progression of their liver disease. Adefovir dipivoxil, an analogue of the nucleotides, is effective for the treatment of patients with resistance to lamivudine. The aim of this study was to evaluate the efficacy, safety and resistance of adefovir dipivoxil in patients with chronic hepatitis B refractory to treatment with lamivudine. PATIENTS AND METHOD: One hundred and twenty hepatits B virus patients refractory to lamivudine were treated with adefovir dipivoxil. Seventy-four patients were followed up during two years. In all cases, the hepatitis B virus-DNA was determined by polymerase chain reaction, and in those cases without response to treatment, the presence of resistances to adefovir and lavimudine were studied. RESULTS: At the second year of treatment, we observed a biological response of 54.1%, a biochemical response of 62.2%, while an elimination of hepatitis B e antigen was seen in 21% cases. 20% patients developed resistance to adefovir dipivoxil, and the most frequent detected mutations were: A181V, A181T and N236T. Drug safety was excellent; in fact, only one adverse effect related to the drug was detected. CONCLUSIONS: Treatment with adefovir dipivoxil for 2 years in mono-therapy in patient who are previously non-responders to lavimudine is associated with a high biochemical and virologycal response with an excellent safety. At the second year of treatment, the adefovir dipivoxil resistance rate is 20%.