Population-Based Testing for Undiagnosed Hepatitis C: A Systematic Review of Economic Evaluations.

BACKGROUND AND OBJECTIVES: Recognising the significant public health threat posed by hepatitis C, international targets have been established by the World Health Organization with the aim of eradicating the hepatitis C virus (HCV) by 2030. With the availability of safe and effective therapies, the greatest challenge to achieving elimination is the identification and treatment of those currently undiagnosed. This systematic review aimed to identify and appraise the international literature on the cost-effectiveness of birth cohort, universal, and age-based general population testing for identifying people with undiagnosed chronic HCV infection. METHODS: A comprehensive literature search was undertaken in Medline, Embase and grey literature sources to identify studies published between 1 January 2000 and 17 July 2020. Retrieved citations were independently reviewed by two reviewers according to pre-defined eligibility criteria. Data extraction and critical appraisal were completed in duplicate. Study quality, relevance and credibility were assessed using the Consensus for Health Economic Criteria and the ISPOR questionnaires. All costs were reported in 2019 Irish Euro following adjustment for inflation and purchasing power parity. Willingness-to-pay (WTP) thresholds of €20,000 and €45,000 were adopted as reference points for interpreting cost-effectiveness in the narrative synthesis. The systematic review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. RESULTS: Overall, 4622 citations were retrieved in the literature search. Of these, 27 studies met the inclusion criteria. Six (22%) of the 27 studies were rated as low quality, 17 (63%) were moderate quality and four (15%) were high quality. Compared with no testing or risk-based testing: 14 of 16 (88%) cost-utility analyses found that birth cohort testing was cost effective, eight of nine (89%) analyses found that universal testing was cost effective, and eight of eight (100%) analyses found that age-based general population testing was cost effective. Cost effectiveness was influenced by disease prevalence and progression, testing and treatment uptake, treatment eligibility of those identified by testing, the cost of treatment and the proportion of those treated that achieve sustained virological response. CONCLUSION: Overall, the international evidence supports the potential cost effectiveness of birth cohort, universal, and age-based general population testing, but is caveated by study generalisability, specifically the transferability of findings from one jurisdiction to another, and institutional variations in healthcare delivery systems and budgetary constraints. The cost effectiveness of each approach will vary according to population- and health system-specific characteristics such as epidemiological context, testing coverage, linkage to care and capacity to treat. Given issues regarding the transferability of economic evaluations (for example, model inputs and assumptions) and the significant resources required to implement these interventions, jurisdiction-specific economic evaluations and budget impact analyses will likely be required to inform investment and implementation decisions. REGISTRATION: PROSPERO, CRD42019127159. Registered 29 April 2019.

Assessing cost-effectiveness of hepatitis C testing pathways in Georgia using the Hep C Testing Calculator.

The cost of testing can be a substantial contributor to hepatitis C virus (HCV) elimination program costs in many low- and middle-income countries such as Georgia, resulting in the need for innovative and cost-effective strategies for testing. Our objective was to investigate the most cost-effective testing pathways for scaling-up HCV testing in Georgia. We developed a Markov-based model with a lifetime horizon that simulates the natural history of HCV, and the cost of detection and treatment of HCV. We then created an interactive online tool that uses results from the Markov-based model to evaluate the cost-effectiveness of different HCV testing pathways. We compared the current standard-of-care (SoC) testing pathway and four innovative testing pathways for Georgia. The SoC testing was cost-saving compared to no testing, but all four new HCV testing pathways further increased QALYs and decreased costs. The pathway with the highest patient follow-up, due to on-site testing, resulted in the highest discounted QALYs (123 QALY more than the SoC) and lowest costs ($127,052 less than the SoC) per 10,000 persons screened. The current testing algorithm in Georgia can be replaced with a new pathway that is more effective while being cost-saving.

Health and economic benefits of achieving hepatitis C virus elimination in Pakistan: A modelling study and economic analysis.

BACKGROUND: Modelling suggests that achieving the WHO incidence target for hepatitis C virus (HCV) elimination in Pakistan could cost US$3.87 billion over 2018 to 2030. However, the economic benefits from integrating services or improving productivity were not included. METHODS AND FINDINGS: We adapt a HCV transmission model for Pakistan to estimate the impact, costs, and cost-effectiveness of achieving HCV elimination (reducing annual HCV incidence by 80% by 2030) with stand-alone service delivery, or partially integrating one-third of initial HCV testing into existing healthcare services. We estimate the net economic benefits by comparing the required investment in screening, treatment, and healthcare management to the economic productivity gains from reduced HCV-attributable absenteeism, presenteeism, and premature deaths. We also calculate the incremental cost-effectiveness ratio (ICER) per disability-adjusted life year (DALY) averted for HCV elimination versus maintaining current levels of HCV treatment. This is compared to an opportunity cost-based willingness-to-pay threshold for Pakistan (US$148 to US$198/DALY). Compared to existing levels of treatment, scaling up screening and treatment to achieve HCV elimination in Pakistan averts 5.57 (95% uncertainty interval (UI) 3.80 to 8.22) million DALYs and 333,000 (219,000 to 509,000) HCV-related deaths over 2018 to 2030. If HCV testing is partially integrated, this scale-up requires an investment of US$1.45 (1.32 to 1.60) billion but will result in US$1.30 (0.94 to 1.72) billion in improved economic productivity over 2018 to 2030. This elimination strategy is highly cost-effective (ICER = US$29 per DALY averted) by 2030, with it becoming cost-saving by 2031 and having a net economic benefit of US$9.10 (95% UI 6.54 to 11.99) billion by 2050. Limitations include uncertainty around what level of integration is possible within existing primary healthcare services as well as a lack of Pakistan-specific data on disease-related healthcare management costs or productivity losses due to HCV. CONCLUSIONS: Investment in HCV elimination can bring about substantial societal health and economic benefits for Pakistan.

Estimating the net value of treating hepatitis C virus using sofosbuvir-velpatasvir in India.

Recently developed direct-acting antiviral (DAA) treatments for hepatitis C virus (HCV) have been groundbreaking for their high efficacy across disease genotypes and lack of severe side effects. This study uses a cost-of-illness (COI) approach to estimate the net value conferred by this class of drugs using the cost and efficacy of one of these novel drug combinations, sofosbuvir and velpatasvir (SOF/VEL), recently licensed for generic manufacture in India. This study considers COI of lifetime earnings lost by patients and potential secondarily infected individuals due to disability and premature death from HCV infection. Expected net benefits of treatment are substantial for non-cirrhotic (NC) and compensated cirrhotic (CC) patients (ranging from 5,98,003 INR for NC women to 1,05,25,504 INR for CC men). Increased earnings are not sufficient to fully offset cost of treatment for decompensated cirrhotic individuals but treatment may still be justified on the basis of the intrinsic value of health improvements and other treatment benefits.

The impact of public coverage of newer hepatitis C medications on utilization, adherence, and costs in British Columbia.

BACKGROUND: Sofosbuvir and ledipasvir-sofosbuvir are both newer direct-acting antiviral agents for the treatment of hepatitis C. The high list prices for both drugs have led to concern about the budget impact for public drug coverage programs. Therefore, we studied the impact of public prescription drug coverage for both drugs on utilization, adherence, and public and private expenditure in British Columbia, Canada. METHODS: We used provincial administrative claims data from January 2014 to June 2017 for all individuals historically tested for either hepatitis C and/or human immunodeficiency virus. Using interrupted time series analysis, we examined the impact of public insurance coverage on treatment uptake, adherence (proportion of days covered), and public and private expenditures. RESULTS: Over our study period, 4,462 treatment initiations were eligible for analysis (1,131 sofosbuvir and 3,331 ledipasvir-sofosbuvir, which include 19 patients initiated on both treatments). We found the start of public coverage for sofosbuvir and ledipasvir-sofosbuvir increased treatment uptake by 154%. Adherence rates were consistently high and did not change with public coverage. Finally, public expenditure increased after the policy change, and crowded out some private expenditure. CONCLUSION: Public coverage for high-cost drugs for hepatitis C dramatically increased use of these drugs, but did not reduce adherence. From a health policy perspective, public payers should be prepared for increased treatment uptake following the availability of public coverage. However, they should not be concerned that populations without private insurance coverage will be less adherent and not finish their treatment course.

Economic and epidemiological evaluation of interventions to reduce the burden of hepatitis C in Yunnan province, China.

BACKGROUND: The paradigm shift in hepatitis C virus (HCV) treatment options in the last five years has raised the prospect of eliminating the disease as a global health threat. This will require a step-change in the number being treated with the new direct-acting antivirals (DAAs). Given constrained budgets and competing priorities, policy makers need information on how to scale-up access to HCV treatment. To inform such decisions, we examined the cost effectiveness of screening and treatment interventions in Yunnan, China. METHODS AND FINDINGS: We simulated the HCV epidemic using a previously published model of HCV transmission and disease progression, calibrated to Yunnan data, and implemented a range of treatment and screening interventions from 2019. We incorporated treatment, diagnosis, and medical costs (expressed in 2019 US Dollars, USD) to estimate the lifetime benefits and costs of interventions. Using this model, we asked: is introducing DAAs cost effective from a healthcare sector perspective; what is the optimal combination of screening interventions; and what is the societal return on investment of intervention? The incremental cost-effectiveness ratio (ICER) of switching to DAAs with a median cost of 7,400 USD (50,000 Chinese Yuan) per course is 500 USD/disability adjusted life year (DALY) averted; at a threshold of 50% of Yunnan gross domestic product (2,600 USD), switching to DAAs is cost effective 94% of the time. At this threshold, the optimal, cost-effective intervention comprises screening people who inject drugs, those in HIV care, men who have sex with men, and ensuring access to DAAs for all those newly diagnosed with HCV. For each USD invested in this intervention, there is an additional 0·80 USD (95% credible interval: 0·17-1·91) returned through reduced costs of disease or increased productivity. Returns on investment are lower (and potentially negative) if a sufficiently long-term horizon, encompassing the full stream of future benefits, is not adopted. The study had two key limitations: costing data were not always specific to Yunnan province but were taken from China-level studies; and modelled interventions may require more operational research to ensure they can be effectively and efficiently rolled-out to the entire province. CONCLUSIONS: Introducing DAAs is cost effective, the optimal package of screening measures is focussed on higher risk groups, and there are likely to be positive returns from investing in such HCV interventions. Our analysis shows that targeted investment in HCV interventions will have net benefits to society; these benefits will only increase as DAA costs fall.

Cost-Effectiveness of Testing and Treatment for Hepatitis B Virus and Hepatitis C Virus Infections: An Analysis by Scenarios, Regions, and Income.

OBJECTIVES: Testing and treatment for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are highly effective, high-impact interventions. This article aims to estimate the cost-effectiveness of scaling up these interventions by scenarios, regions, and income groups. METHODS: We modeled costs and impacts of hepatitis elimination in 67 low- and middle-income countries from 2016 to 2030. Costs included testing and treatment commodities, healthcare consultations, and future savings from cirrhosis and hepatocellular carcinomas averted. We modeled disease progression to estimate disability-adjusted life-years (DALYs) averted. We estimated incremental cost-effectiveness ratios (ICERs) by regions and World Bank income groups, according to 3 scenarios: flatline (status quo), progress (testing/treatment according to World Health Organization guidelines), and ambitious (elimination). RESULTS: Compared with no action, current levels of testing and treatment had an ICER of $807/DALY for HBV and -$62/DALY (cost-saving) for HCV. Scaling up to progress scenario, both interventions had ICERs less than the average gross domestic product/capita of countries (HBV: $532/DALY; HCV: $613/DALY). Scaling up from flatline to elimination led to higher ICERs across countries (HBV: $927/DALY; HCV: $2528/DALY, respectively) that remained lower than the average gross domestic product/capita. Sensitivity analysis indicated discount rates and commodity costs were main factors driving results. CONCLUSIONS: Scaling up testing and treatment for HBV and HCV infection as per World Health Organization guidelines is a cost-effective intervention. Elimination leads to a much larger impact though ICERs are higher. Price reduction strategies are needed to achieve elimination given the substantial budget impact at current commodity prices.

HEPCARE EUROPE- A case study of a service innovation project aiming at improving the elimination of HCV in vulnerable populations in four European cities.

OBJECTIVES: Hepatitis C Virus (HCV) is a significant cause of chronic liver disease. Among at-risk populations, access to diagnosis and treatment is challenging. We describe an integrated model of care, Hepcare Europe, developed to address this challenge. METHODS: Using a case-study approach, we describe the cascade of care outcomes at all sites. Cost analyses estimated the cost per person screened and linked to care. RESULTS: A total of 2608 participants were recruited across 218 clinical sites. HCV antibody test results were obtained for 2568(98•5%); 1074(41•8%) were antibody-positive, 687(60•5%) tested positive for HCV-RNA, 650(60•5%) were linked to care, and 319(43•5%) started treatment. 196(61•4%) of treatment initiates achieved a Sustained Viral Response (SVR) at dataset closure, 108(33•9%) were still on treatment, eight (2•7%) defaulted from treatment, and seven (2•6%) had virologic failure or died. The cost per person screened varied from €194 to €635, while the cost per person linked to care varied from €364 to €2035. CONCLUSIONS: Hepcare enhanced access to HCV treatment and cure, and costs were affordable in all settings, offering a framework for scale-up and reproducibility.

Hepatitis C Virus Infection as a Predictor of Complications and Increased Costs Following Primary Lumbar Fusion Surgery.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The aim of this study was to identify whether hepatitis C virus (HCV) diagnosis influences in-hospital lengths of stay (LOS), postoperative complications, readmission rates, or costs following primary posterior lumbar fusions in an elective setting. SUMMARY OF BACKGROUND DATA: Although joint arthroplasty literature has shown increased complication rates and costs for patients seropositive with HCV without liver disease compared to those without HCV, this comorbidity has not been explored in the spine literature. To our knowledge, this is the first publication in the lumbar spine literature to solely focus on HCV as the disease burden. METHODS: A national database was queried for patients who underwent primary lumbar spine fusion for degenerative lumbar pathology with Medicare insurance from 2005 to 2014. The 90-day postoperative complication rates, readmission rates, and treatment costs were queried. To limit confounding, HCV patients were matched with a control cohort of non-HCV patients using patient demographics, treatment modality, and comorbid conditions, and then analyzed by multivariate logistic regression. Patients with active liver disease were excluded to better isolate HCV as the comorbidity. RESULTS: A cohort of 28,841 patients were included in the final analysis. Postoperatively, compared to those without HCV infection, those with HCV had significantly higher odds of blood transfusions (odds ratio [OR]: 3.06), pneumonia (OR: 2.49), respiratory failure (OR: 2.49), urinary tract infections (OR: 1.89), wound-/implant-related infections (OR: 1.74), cerebrovascular events (OR: 1.70), or any postoperative complication within 90 days (OR: 2.93; all P < 0.0001). Furthermore, HCV positive patients had higher day of surgery costs ($28,713.26 vs. $25,448.26, P < 0.0001) and 90-day costs ($33,447.39 vs. $29,016.77, P < 0.0001). There was not a significant difference for patients with HCV infection compared to those without in regard to hospital LOS (10 days vs. 8 days, P = 0.332) and rates of a 90-day readmission (0.37% vs. 0.22%; OR: 1.70, 95% confidence interval: 1.00-2.90, P: 0.050). CONCLUSION: In patients undergoing primary lumbar fusion, a seropositivity for HCV without liver disease is associated with higher costs and complication rates, including higher rates of blood transfusion requirements and pneumonia-related complications. This data shed new light on elective spine surgery in HCV patients and may influence the risks and benefits considerations for surgeons considering lumbar fusion in this population. LEVEL OF EVIDENCE: 3.

Association of Direct-Acting Antiviral Therapy for Hepatitis C With After-Treatment Costs Among Medicare Beneficiaries.

Importance: Direct-acting antiviral (DAA) therapy for hepatitis C is highly effective but expensive. Evidence is scarce on whether DAA therapy reduces downstream medical costs. Objective: To examine the association of DAA therapy with posttreatment medical costs among Medicare beneficiaries. Design, Setting, and Participants: This retrospective cohort study obtained data from various Medicare claims files for 2013 to 2017. The study population comprised patients with a hepatitis C diagnosis in 2014 who were enrolled in fee-for-service Medicare and Part D. Multivariate regression models were used to compare changes in medical costs over a 30-month posttreatment follow-up period between patients who used DAA therapy (treatment group) and a propensity score-matched cohort of patients who did not use DAA (control group). The model was estimated separately for patients with and those without cirrhosis. Data were analyzed between September 1, 2019, and March 31, 2020. Exposures: Completion of DAA therapy. Main Outcomes and Measures: Two outcomes were established: hepatitis C or liver disease-related costs and total medical costs. Costs were measured by Medicare-allowed payments, which included Medicare reimbursements, patient responsibilities, and third-party payments. Results: A propensity score-matched cohort of 15 198 patients (9038 men [59.5%]; mean [SD] age, 60.2 [10.8] years) was analyzed. During the first 6 months after DAA therapy, hepatitis C or liver disease-related costs decreased by $2498 (95% CI, -$3356 to -$1640) in patients with cirrhosis and by $486 (95% CI, -$603 to -$369) in patients without cirrhosis compared with control or untreated patients. Cumulative reductions in hepatitis C or liver disease-related costs during 30 months after DAA treatment were $15 808 (95% CI, -$22 530 to -$9085) in patients with cirrhosis and $5372 (95% CI, -$6384 to -$4360) in patients without cirrhosis. Among those who used DAA therapy compared with control patients, total medical costs decreased by $2905 (95% CI, -$4832 to -$979) in patients with cirrhosis and by $1287 (95% CI, -$2393 to -$283) in patients without cirrhosis during the first 6 months after DAA therapy. No statistically significant association was found between DAA therapy and total medical cost reductions after 12 months of follow-up. Cumulative reductions in total costs during 30 months after DAA therapy were $7074 (95% CI, -$18 448 to $4298) in patients with cirrhosis and $7497 (95% CI, -$14 287 to -$709) in patients without cirrhosis. Conclusions and Relevance: This study reported that DAA therapy appeared to be associated with a decrease in hepatitis C or liver disease-related costs for 30 months after treatment and with reduction in total medical costs for only 12 months after treatment in patients with or without cirrhosis. Longer-term follow-up studies with diverse outcomes are necessary to assess the value of DAA therapy.

The Ethics of Precision Rationing: Human Genetics and the Need for Debate on Stratifying Access to Medication.

Rising prices for new, transformative therapies are challenging health systems around the world, leading many payers and providers to begin rationing access to treatments, even in the countries that have been most resistant to doing so. This is the case for direct-acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV). However, little attention has been paid to the increasing role that human genetics might play in rationing decisions. Researchers have already proposed that genetic markers associated with spontaneous HCV clearance could be used to restrict DAA access for some patients, although treatment would be medically beneficial for those patients. Would such forms of rationing present a form of genetic discrimination? And what of the public health implications of these approaches? Here we present an ethical analysis of such proposals for "precision rationing" and raise 4 key areas of concern. We argue that ethical issues arising in this area are not substantively different from the pressing ethical issues regarding rationing and discrimination more broadly, but provide important impetus for motivating broad public debate to find ethically sound ways of managing genomics and new expensive medications.

A tool to measure the impact of inaction toward elimination of hepatitis C: A case study in Korea.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) and its sequelae present a significant source of economic and societal burden. Introduction of highly effective curative therapies has made HCV elimination attainable. The study used a predictive model to assess the clinical and economic impact of implementing national screening and treatment policies toward HCV elimination in Korea. METHODS: A previously validated Markov disease progression model of HCV infection was employed to analyze the clinical and economic impact of various strategies for HCV diagnosis and treatment in Korea. In this analysis, the model compared the clinical and economic outcomes of current HCV-related interventions in Korea (7,000 patients treated and 4,200 patients newly diagnosed annually, starting in 2017) to four elimination scenarios: 1) initiating sufficient diagnosis and treatment interventions to meet the World Health Organization's GHSS elimination targets by 2030, 2) delaying initiation of interventions by one year, 3) delaying initiation of interventions by two years and 4) accelerating initiation of interventions to meet elimination targets by 2025. Modelled historical incidence of HCV was calibrated to match a viremic HCV prevalence of 0.44% in 2009. Elimination scenarios required 24,000 treatments and 34,000 newly diagnosed patients annually, starting in 2018, to reach the 2030 targets. RESULTS: Compared to current "status quo" interventions, elimination (or accelerated elimination by 2025) would avert 23,700 (27,000) incident cases of HCV, 1,300 (1,400) liver-related deaths (LRDs) and 2,900 (3,100) cases of end-stage liver disease (ESLD) over the 2017-2030 time period. Postponing interventions by one (or two) years would avert 21,100 (18,600) new HCV infections, 920 (660) LRDs and 2,000 (1,400) cases of ESLD by 2030. Following elimination or accelerated elimination strategies would save 860 million USD or 1.1 billion USD by 2030, respectively, compared to the status quo, requiring an up-front investment in prevention that decreases spending on liver-related complications and death. CONCLUSIONS: By projecting the impact of interventions and tracking progress toward GHSS elimination targets using modelling, we demonstrate that Korea can prevent significant morbidity, mortality and spending on HCV. Results should serve as the backbone for policy and decision-making, demonstrating how aggressive prevention measures are designed to reduce future costs and increase the health of the public.

Trends in the Burden of Chronic Liver Disease Among Hospitalized US Adults.

Importance: One factor associated with the rapidly increasing clinical and economic burden of chronic liver disease (CLD) is inpatient health care utilization. Objective: To understand trends in the hospitalization burden of CLD in the US. Design, Setting, and Participants: This cross-sectional study of hospitalized adults in the US used data from the National Inpatient Sample from 2012 to 2016 on adult CLD-related hospitalizations. Data were analyzed from June to October 2019. Main Outcomes and Measures: Hospitalizations identified using a comprehensive review of CLD-specific International Classification of Diseases, Ninth Revision, Clinical Modification and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes. Survey-weighted annual trends in national estimates of CLD-related hospitalizations, in-hospital mortality, and hospitalization costs, stratified by demographic and clinical characteristics. Results: This study included 1 016 743 CLD-related hospitalizations (mean [SD] patient age, 57.4 [14.4] years; 582 197 [57.3%] male; 633 082 [62.3%] white). From 2012 to 2016, the rate of CLD-related hospitalizations per 100 000 hospitalizations increased from 3056 (95% CI, 3042-3069) to 3757 (95% CI, 3742-3772), and total inpatient hospitalization costs increased from $14.9 billion (95% CI, $13.9 billion to $15.9 billion) to $18.8 billion (95% CI, $17.6 billion to $20.0 billion). Mean (SD) patient age increased (56.8 [14.2] years in 2012 to 57.8 [14.6] years in 2016) and, subsequently, the proportion with Medicare also increased (41.7% [95% CI, 41.1%-42.2%] to 43.6% [95% CI, 43.1%-44.1%]) (P for trend < .001 for both). The proportion of hospitalizations of patients with hepatitis C virus was similar throughout the period of study (31.6% [95% CI, 31.3%-31.9%]), and the proportion with alcoholic cirrhosis and nonalcoholic fatty liver disease showed increases. The mortality rate was higher among hospitalizations with alcoholic cirrhosis (11.9% [95% CI, 11.7%-12.0%]) compared with other etiologies. Presence of hepatocellular carcinoma was also associated with a high mortality rate (9.8% [95% CI, 9.5%-10.1%]). Cost burden increased across all etiologies, with a higher total cost burden among hospitalizations with alcoholic cirrhosis ($22.7 billion [95% CI, $22.1 billion to $23.2 billion]) or hepatitis C virus ($22.6 billion [95% CI, $22.1 billion to $23.2 billion]). Presence of cirrhosis, complications of cirrhosis, and comorbidities added to the CLD burden. Conclusions and Relevance: Over the study period, the total estimated national hospitalization costs in patients with CLD reached $81.1 billion. The inpatient CLD burden in the US is likely increasing because of an aging CLD population with increases in concomitant comorbid conditions.

Estimating the price at which hepatitis C treatment with direct-acting antivirals would be cost-saving in Japan.

In Japan, 1.5-2 million people are chronically infected with hepatitis C virus (HCV) infection. New direct-acting antiviral agents (DAA) offer an unprecedented opportunity to cure HCV. While the price of HCV treatment decreased recently in most countries, it remains one of the highest in Japan. Our objective was to evaluate the cost-effectiveness of HCV treatment in patients of different age groups and to estimate the price at which DAAs become cost-saving in Japan. A previously developed microsimulation model was adapted to the Japanese population and updated with Japan-specific health utilities and costs. Our model showed that compared with no treatment, the incremental cost-effectiveness ratio (ICER) of DAAs at a price USD 41,046 per treatment was USD 9,080 per quality-adjusted life year (QALY) gained in 60-year-old patients. HCV treatment became cost-effective after 9 years of starting treatment. However, if the price of DAAs is reduced by 55-85% (USD 6,730 to 17,720), HCV treatment would be cost-saving within a 5 to 20-year time horizon, which should serve to increase the uptake of DAA-based HCV treatment. The payers of health care in Japan could examine ways to procure DAAs at a price where they would be cost-saving.

Cost effectiveness of an intervention to increase uptake of hepatitis C virus testing and treatment (HepCATT): cluster randomised controlled trial in primary care.

OBJECTIVE: To evaluate the effectiveness and cost effectiveness of a complex intervention in primary care that aims to increase uptake of hepatitis C virus (HCV) case finding and treatment. DESIGN: Pragmatic, two armed, practice level, cluster randomised controlled trial and economic evaluation. SETTING AND PARTICIPANTS: 45 general practices in South West England (22 randomised to intervention and 23 to control arm). Outcome data were collected from all intervention practices and 21/23 control practices. Total number of flagged patients was 24 473 (about 5% of practice list). INTERVENTION: Electronic algorithm and flag on practice systems identifying patients with HCV risk markers (such as history of opioid dependence or HCV tests with no evidence of referral to hepatology), staff educational training in HCV, and practice posters/leaflets to increase patients' awareness. Flagged patients were invited by letter for an HCV test (with one follow-up) and had on-screen pop-ups to encourage opportunistic testing. The intervention lasted one year, with practices recruited April to December 2016. MAIN OUTCOME MEASURES: Primary outcome: uptake of HCV testing. SECONDARY OUTCOMES: number of positive HCV tests and yield (proportion HCV positive); HCV treatment assessment at hepatology; cost effectiveness. RESULTS: Baseline HCV testing of flagged patients (six months before study start) was 608/13 097 (4.6%) in intervention practices and 380/11 376 (3.3%) in control practices. During the study 2071 (16%) of flagged patients in the intervention practices and 1163 (10%) in control practices were tested for HCV: overall intervention effect as an adjusted rate ratio of 1.59 (95% confidence interval 1.21 to 2.08; P<0.001). HCV antibodies were detected in 129 patients from intervention practices and 51 patients from control practices (adjusted rate ratio 2.24, 1.47 to 3.42) with weak evidence of an increase in yield (6.2% v 4.4%; adjusted risk ratio 1.40, 0.99 to 1.95). Referral and assessment increased in intervention practices compared with control practices (adjusted rate ratio 5.78, 1.6 to 21.6) with a risk difference of 1.3 per 1000 and a "number needed to help" of one extra HCV diagnosis, referral, and assessment per 792 (95% confidence interval 558 to 1883) patients flagged. The average cost of HCV case finding was £4.03 (95% confidence interval £2.27 to £5.80) per at risk patient and £3165 per additional patient assessed at hepatology. The incremental cost effectiveness ratio was £6212 per quality adjusted life year (QALY), with 92.5% probability of being below £20 000 per QALY. CONCLUSION: HepCATT had a modest impact but is a low cost intervention that merits optimisation and implementation as part of an NHS strategy to increase HCV testing and treatment. TRIAL REGISTRATION: ISRCTN61788850.

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.