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In 2016, the Hepatitis B and C Public Policy Association (HepBCPPA), gathered all the main stakeholders in the field of hepatitis C virus (HCV) to launch the now landmark HCV Elimination Manifesto, calling for the elimination of HCV in the EU by 2030. Since then, many European countries have made progress towards HCV elimination. Multiple programmes—from the municipality level to the EU level—were launched, resulting in an overall decrease in viremic HCV infections and liver-related mortality. However, as of 2021, most countries are not on track to reach the 2030 HCV elimination targets set by the WHO. Moreover, the COVID-19 pandemic has resulted in a decrease in HCV diagnoses and fewer direct-acting antiviral treatment initiations in 2020. Diagnostic and therapeutic tools to easily diagnose and treat chronic HCV infection are now well established. Treating all patients with chronic HCV infection is more cost-saving than treating and caring for patients with liver-related complications, decompensated cirrhosis or hepatocellular carcinoma. It is more important than ever to reinforce and scale-up action towards HCV elimination. Yet, efforts urgently need the dedicated commitment of policymakers at all governmental and policy levels. Therefore, the third EU Policy Summit, held in March 2021, featured EU parliamentarians and other key decision makers to promote dialogue and take strides towards securing wider EU commitment to advance and achieve HCV elimination by 2030. We have summarized the key action points and reported the ‘Call-to-Action’ statement supported by all the major relevant European associations in the field.

Background and aims: Severe liver disease markers assessed before HCV eradication are acknowledged to usually improve after the SVR. We prospectively evaluated, in the PITER cohort, the long-term HCC risk profile based on predictors monitored after HCV eradication by direct-acting antivirals in patients with cirrhosis. Methods: HCC occurrence was evaluated by Kaplan-Meier analysis. Cox regression analysis identified the post-treatment variables associated with de-novo HCC; their predictive power was presented in a nomogram. Results: After the end of therapy (median follow-up:28.47 months), among 2064 SVR patients, 119 (5.8%) developed de-novo HCC. The HCC incidence was 1.90%, 4.21%, 6.47% at 12-, 24- and 36-months from end-of-therapy, respectively (incidence rate 2.45/100 person-years). Age, genotype 3, diabetes, platelets (PLT)≤120,000/µl and albumin ≤3.5g/dl levels were identified as pre-treatment HCC independent predictors. Adjusting for age, the post-treatment PLT≤120,000/µl (AdjHR 1.92; 95%CI:1.06-3.45) and albumin≤3.5g/dl (AdjHR 4.38; 95%CI 2.48-7.75) values were independently associated with HCC occurrence. Two different risk profiles were identified by combining long-term post-therapy evaluation of PLT ≤ vs. >120,000/µl and albumin ≤ vs. >3.5g/dl showing a significant different HCC incidence rate of 1.35 vs. 3.77/100 p-y, respectively. Conclusions: The nomogram score based on age, PLT and albumin levels after SVR showed an accurate prediction capability and may support the customizing management for early HCC detection.

Background The aim was to evaluate the hepatitis C virus (HCV) cascade of care in the general population (GP) and in two high-risk populations: patients with diabetes mellitus (DM) and substance users (AS) in treatment in Reggio Emilia Province, Italy. Methods A population-based cross-sectional study was conducted that included 534,476 residents of the Reggio Emilia Province, of whom 32,800 were DM patients and 2726 AS patients. Age-adjusted prevalence was calculated using the direct method of adjustment based on the age-specific structure of EU population. Results The prevalence of HCV testing was 11.5%, 13.8%, and 47.8% in GP, DM, and AS patients respectively, while HCV prevalence was 6.5/1000, 12.6/1000, and 167/1000, respectively. The prevalence of HCV RNA positivity was 4.4/1000, 8.7/1000, and 114/1000 in the three populations, respectively. The rates of HCV RNA-positive individuals not linked to care were 27.9%, 27.3%, and 26% in GP, DM, and AS patients, respectively, while the rates of those cured or cleared were 70.9%, 71%, and 69.9%, respectively. The prevalence of HCV testing was higher for females of reproductive age than for males the same age: 218.4/1000 vs. 74.0/1000, respectively. While more foreigners than Italians underwent the HCV test and were HCV positive, fewer foreigners than Italians received HCV treatment and were cured. Conclusions The low HCV testing and linkage to care rates remain an important gap in the HCV cascade of care in Northern Italy. The prevalence of cured/cleared residents remains lower among foreigners than among Italians.

At a time when hepatitis C virus clearance can be obtained by DAAs in almost all infected patients, global infection burden control is an objective within reach, even if achieving the WHO HCV elimination targets by 2030 may not be attainable. 1 The lowest cost intervention is an awareness campaign to bring in those who are recently diagnosed and those who were previously diagnosed but not treated. Only 30% of all HCV‐diagnosed patients are linked‐to‐care. 2 The next level of intervention is case‐finding for disease control and screening. Screening invites people who do not have symptoms to undergo testing, whereas health professionals are focused on detecting conditions as early as possible among people with symptoms to avoid late clinical presentation. 3 , 4 With continuous efforts for disease control as a priority, early diagnosis in those with liver disease, but unknown HCV status, is the key intervention to avoid further disease progression and costs

Although Italy has been on track for Hepatitis C Virus (HCV) elimination since 2019, it fell off track due to the decrease in the number of treated patients. HCV elimination in Italy will be possible if immediate action is taken. A health policy was implemented beginning in 2021, consisting of screening among key populations and birth cohorts (1969-1989), estimated to have a high prevalence of undiagnosed individuals. The active screening requires regional governance that manages the processes' complexity integrating a well-organized network between territory assistance and hospital to achieve an effective HCV care cascade. This document aims to support the regional decision-making process by defining paths for screening and linkage-to-care. Implementing active screening strategies beyond a risk-based approach is required as a General Practitioners' task. Simplified paths must be drawn for the key populations screening. The infrastructure built for COVID-19 vaccination could be used also for HCV screening. According to a multidisciplinary care delivery, screening should be supplemented with rapid linkage-to-care and treatment of newly diagnosed patients. The realization of the proactive screening during the first two years is vital because it will define the tracks for the whole HCV cost-effective screening of 1948-1988 birth cohorts in Italy.

This study provides an update on hepatitis C virus (HCV) estimates across Italy up to January 2021. A mathematical probabilistic modelling approach, including a Markov chain for liver disease progression, was used to estimate current HCV viraemic burden. Prevalence was defined by geographic area using an estimated annual historical HCV incidence by age, treatment, and migration rate from the Italian National database (ISTAT). Viraemic infection was estimated for the main HCV transmission routes by stages F0-F3 (patients without liver cirrhosis, i.e., potentially asymptomatic liver disease) and F4 (patients with liver cirrhosis, i.e., potentially symptomatic liver disease). By January 2021, we estimated that there were 398,610 individuals in Italy with active HCV infection (prevalence of 0.66%; 95% CI: 0.66-0.67), of which 287,730 (0.48%; 95% CI: 0.46-0.59%) were stage F0-F3. Prevalence values for all individuals with active HCV infection were: North 0.54% (95% CI: 0.53-0.54%), Central 0.88% (95% CI: 0.87-0.89%), South 0.72% (95% CI: 0.71-0.73%), and the Isles 0.67% (95% CI: 0.66-0.68%). The population at risk for previous/current drug injection accounted for 48.6% of all individuals with active HCV infection. A modelling approach such as this to estimate and update the prevalence of active HCV infection could be a useful methodology for the evaluation of healthcare policies related to HCV elimination plans.

Background and Aims: Mixed cryoglobulinemia is the most common HCV extrahepatic manifestation. We aimed to prospectively evaluate the cryoglobulinemic vasculitis (CV) clinical profile after a sustained virologic response (SVR) over a medium-term to long-term period. Approach and Results: Direct-acting antiviral–treated cryoglobulinemic patients, consecutively enrolled in the multicentric Italian Platform for the Study of Viral Hepatitis Therapy cohort, were prospectively evaluated. Cumulative incidence Kaplan-Meier curves were reported for response, clinical deterioration, relapse and relapse-free survival rates. Cox regression analysis evaluated factors associated with different outcomes. A clinical response was reported in at least one follow-up point for 373 of 423 (88%) patients with CV who achieved SVR. Clinical response increased over time with a 76% improvement rate at month 12 after the end of treatment. A full complete response (FCR) was reached by 164 (38.8%) patients in at least one follow-up point. CV clinical response fluctuated, with some deterioration of the initial response in 49.6% of patients (median time of deterioration, 19months). In patients who achieved FCR and had an available follow-up (137 patients) a relapse was observed in 13% and it was transient in 66.7% of patients. The rate of patients without any deterioration was 58% and 41% at 12 and 24months, respectively. After achieving SVR, a clinical nonresponse was associated with older age and renal involvement; a clinical deterioration/relapse was associated with high pretreatment rheumatoid factor values, and FCR was inversely associated with age, neuropathy, and high cryocrit levels. Conclusion: In patients with CV, HCV eradication may not correspond to a persistent clinical improvement, and clinical response may fluctuate. This implies an attentive approach to post-SVR evaluation through prognostic factors and tailored treatment.

Objectives: Optimized diagnostic algorithms to detect active infections are crucial to achieving HCV elimination. We evaluated the cost effectiveness and sustainability of different algorithms for HCV active infection diagnosis, in a context of a high endemic country for HCV infection. Methods: A Markov disease progression model, simulating six diagnostic algorithms in the birth cohort 1969‐1989 over a 10‐year horizon from a healthcare perspective was used. Conventionally diagnosis of active HCV infection is through detection of antibodies (HCV‐Ab) detection followed by HCV‐RNA or HCV core antigen (HCV‐Ag) confirmatory testing either on a second sample or by same sample reflex testing. The undiagnosed and unconfirmed rates were evaluated by assays false negative estimates and each algorithm patients’ drop‐off. Age, liver disease stages distribution, liver disease stage costs, treatment effectiveness and costs were used to evaluate the quality‐adjusted life‐years (QALYs) and the incremental cost‐effectiveness ratios (ICER). Results: The reference option was Rapid HCV‐Ab followed by second sample HCV‐Ag testing which produced the lowest QALYs (866,835 QALYs). The highest gains in health (QALYs=974,458) was obtained by HCV‐RNA reflex testing which produced a high cost‐effective ICER (€891/QALY). Reflex testing (same sample‐single visit) vs two patients’ visits algorithms, yielded the highest QALYs and high cost‐effective ICERs (€566 and €635/QALY for HCV‐Ag and HCV‐RNA, respectively), confirmed in 99.9% of the 5,000 probabilistic simulations. Conclusions: Our data confirm, by a cost effectiveness point of view, the EASL and WHO clinical practice guidelines recommending HCV reflex testing as most cost effective diagnostic option vs other diagnostic pathways.

Italy has been one of the countries with the greatest burden of HCV in Western Europe and with the highest number of HCV liver-related deaths. In order to achieve HCV elimination by 2030 Italy, like many other countries, will need to succeed in tackling the undiagnosed individuals with active HCV infection. To this aim beginning in 2021, a nationwide action has been implemented, consisting of the performance of screening tests among key populations and birth cohorts (1969-1989), estimated to have a high prevalence of undiagnosed individuals. The realization of the proactive screening during the first two years will define the tracks for the whole optimized screening strategy, including also the screening of 1948-1968 birth cohorts, reported to be the best cost-effective strategy in achieving the HCV elimination targets by 2030 in Italy. Each Italian region needs to define the present and future steps to reach HCV elimination goal by 2030 guaranteeing the equity of care.

The World Health Organization (WHO) HBV and HCV elimination targets, set in 2016 and based on projections to 2030, were unable to consider the impact of intervening factors. To evaluate the impact of the COVID-19 pandemic on viral hepatitis elimination programs, the European Association for the Study of the Liver (EASL) conducted a survey in liver centers worldwide in 2021.A web-based questionnaire was distributed (May-July 2021) to all EASL members representing clinical units providing HBV and HCV hepatitis care. Results are expressed as absolute numbers and reduction rates for each care activity.Data were collected from 32 European and 12 non-European clinical centers. Between January 2019 (pre-pandemic) and December 2020 (during the pandemic), chronic HBV consultations decreased by 32% and 26%, new referrals by 38% and 39%, HBV testing rates by 39% and 21% (for HBsAg detection) and 30% and 22% (for HBV DNA detection), and new HBV treatments by 20% and 44% (All steps in the viral hepatitis care cascade have been hampered by the COVID-19 pandemic, with a comparable impact across different centers. These data reaffirm the pandemic's major effect on global viral hepatitis elimination programs and suggest that actions to achieve the WHO 2030 targets should be reconsidered and revised to account for each country's progress relative to pre-pandemic values.The EASL multinational survey conclusively shows that viral hepatitis elimination programs, expected to provide control of hepatitis B and hepatitis C worldwide by 2030, have been held back by the COVID-19 pandemic in clinical centers from several European and non-European countries, with a comparable impact across centers. Limitations in the cascade of care for both HBV and HCV were linked to limited access to screening, consultations, specific testing, and actual treatment. As restrictions for COVID-19 begin to lift, efforts to diagnose and provide treatment for viral hepatitis should remain high on the list of priorities for public health officials to maintain the WHO elimination efforts. Measures that have been put in place to control the COVID-19 pandemic could be transferred to increasing the diagnosis and linkage to care of people with hepatitis.

Not available.

Background Although an increase in hepatitis C virus (HCV) prevalence from Northern to Southern Italy has been reported, the burden of asymptomatic individuals in different Italian regions is currently unknown. Methods A probabilistic approach, including a Markov chain for liver disease progression, was applied to estimate current HCV viraemic burden. The model defined prevalence by geographic area using an estimated annual historical HCV incidence by age, treatment rate, and migration rate from the Italian National database. Viraemic infection by age group was estimated for each region by main HCV transmission routes of individuals for stage F0–F3 (i.e. patients without liver cirrhosis and thus potentially asymptomatic) and F4 (patients with liver cirrhosis, thus potentially symptomatic). Results By January 2020, it was estimated that there were 409,184 Italian individuals with HCV (prevalence of 0.68%; 95% CI: 0.54–0.82%), of which 300,171 (0.50%; 95% CI: 0.4–0.6%) were stage F0–F3. Considering all individuals with HCV in stage F0–F3, the geographical distributions (expressed as the proportion of HCV infected individuals by macroarea within the overall estimated number of F0–F3 individuals and prevalence values, expressed as the percentage of individuals with HCV versus the overall number of individuals for each macroarea) were as follows: North 42.1% (0.45%; 95% CI: 0.36–0.55%), Central 24.1% (0.61%; 95% CI: 0.48–0.74%), South 23.2% (0.50%; 95% CI: 0.4–0.61%), and the Isles 10.6% (0.49%; 95% CI: 0.39–0.59%). The population of people who inject drugs accounted for 50.4% of all individuals infected (F0–F3). Undiagnosed individuals (F0–F3) were ~ 15 years younger (⁓ 50 years) compared with patients with stage F4 (⁓ 65 years), with similar age distributions across macroareas. In contrast to what has been reported on HCV epidemiology in Italy, an increasing trend in the proportion of potentially undiagnosed individuals with HCV (absolute number within the F0–F3) from South (23.2%) to North (42.1%) emerged, independent of similar regional prevalence values. Conclusion This targeted approach, which addresses the specific profile of undiagnosed individuals, is helpful in planning effective elimination strategies by region in Italy and could be a useful methodology for other countries in implementing their elimination plans.

Background The universal treatment of diagnosed patients with chronic HCV infection has been widely conducted in Italy since 2017. However, the pool of individuals diagnosed but yet to be treated in Italy has been estimated to end around 2025, leaving a significant proportion of infected individuals undiagnosed/without care. Estimates of this population are currently unknown. Methods A probabilistic modelling approach was applied to estimate annual historical HCV incident cases by their age-group (0–100 years) distribution from available literature and Italian National database (1952 to October 2019). Viraemic infection rates were modelled on the main infection routes in Italy: people who inject drugs (PWID), tattoos, sexual transmission, glass syringe use, blood transfusion and vertical transmission. Annual liver fibrosis stage transition probabilities were modelled using a Markov model. The number of HCV viraemic asymptomatic (fibrosis stage F0-F3:potentially undiagnosed/unlinked to care) and symptomatic (fibrosis stage F4: potentially linked to care) individuals was estimated. Results By October 2019, total viraemic HCV individuals in Italy (excluding treated patients since 1992) were estimated to be 410,775 (0.68 % of current population of Italy; 95 % CI: 0.64−0.71%, based on the current Italian population), of which 281,809 (0.47 %; 95 % CI:0.35−0.60%) were fibrosis stage F0-F3. Among different high risk groups in stage F0-F3, the following distribution was estimated: PWID; 52.0 % (95 % CI:37.9–66.6 %), tattoo; 28.8 % (95 % CI:23–32.3 %), sexual transmission; 12.0 % (95 % CI:9.6–13.7 %), glass syringe and transfusion; 6.4 % (95 % CI:2.4–17.8 %), and vertical transmission; 0.7 % (95 % CI:0.4–1.2 %). Conclusion Under the assumption that most untreated HCV-infected individuals with stage F0-F3 are undiagnosed, more than 280,000 individuals are undiagnosed and/or unlinked to care in Italy. Marked heterogeneity across the major routes of HCV transmission was estimated. This modelling approach may be a useful tool to characterise the HCV epidemic profile also in other countries, based on country specific epidemiology and HCV main transmission routes.

The World Health Organization (WHO) targets for eliminating HCV by 2030 may be overambitious for many high-income countries. Recent analyses (ie, data from 2017 to 2019) show that only 11 countries are on track for meeting WHO’s elimination targets. For a country to be truly on track, it is important that the majority of infected individuals be identified and treated. There is still a need for country and population-specific evaluations within the different HCV screening and treatment strategies available, in order to assess their cost-effectiveness and sustainability and support an evidence-based policy for HCV elimination. Any health policy model is affected by the diversity and quality of the available data and by gaps in data. Given the differences among countries, comparing progress based on fixed global targets will not necessarily be suitable in the same measure for each country. In a recent document, the European Collaborators of Polaris Observatory provide insight into the limitations of the current WHO targets. The absolute targets identified by each country in accordance with the measures set by WHO would be essential in reaching the HCV elimination. All analytic models to assess the progress towards HCV elimination are based on projections to 2030 not including the impact of the COVID-19 pandemic on hepatitis-related services. With specific regard to the achievement of WHO hepatitis elimination goals, all measures that will be put in place during and after COVID-19 pandemic could be transferred in increasing diagnosis and linkage to care of people with hepatitis.

The 69th World Health Assembly endorsed the Global Health Sector Strategy for Viral Hepatitis, embracing a goal to eliminate hepatitis infection as a public health threat by 2030. This was followed by the World Health Organization's (WHO) global targets for the care and management of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. These announcements and targets were important in raising awareness and calling for action; however, tracking countries’ progress towards these elimination goals has provided insights to the limitations of these targets. The existing targets compare a country's progress relative to its 2015 values, penalizing countries who started their programmes prior to 2015, countries with a young population, or countries with a low prevalence. We recommend that (1) WHO simplify the hepatitis elimination targets, (2) change to absolute targets and (3) allow countries to achieve these disease targets with their own service coverage initiatives that will have the maximum impact. The recommended targets are as follows: reduce HCV new chronic cases to ≤5 per 100000, reduce HBV prevalence among 1-year-olds to ≤0.1%, reduce HBV and HCV mortality to ≤5 per 100000, and demonstrate HBV and HCV year-to-year decrease in new HCV- and HBV-related HCC cases. The objective of our recommendations is not to lower expectations or diminish the hepatitis elimination standards, but to provide clearer targets that recognize the past and current elimination efforts by countries, help measure progress towards true elimination, and motivate other countries to follow suit.

Aim To evaluate the cost-consequences of the investment for anti-hepatitis C virus (HCV) treatment by the Italian National Health System (NHS) for patients who will be newly diagnosed through active HCV screening, implemented in Italy from 2020. Methods A previously published Markov model was used to estimate the disease complications avoided and the associated savings over 20 years to treat a standardised population of 10,000 HCV-infected patients diagnosed as a result of screening. Disease progression probabilities and fibrosis stage distribution were based on previously reported data in the literature. Real-life treatment effectiveness and medical expenses for disease management were estimated starting from a representative cohort of HCV-treated patients in Italy (Italian Platform for the Study of Viral Hepatitis Therapies). The breakeven point in time (BPT) was defined as the years required for the initial investment in treatment to be recovered in terms of cumulative costs saved. Results Over a 20-year time horizon, the treatment of 10,000 standardized patients diagnosed through active HCV screening results in 7769 avoided events of progression, which are associated with €838.73 million net savings accrued by the Italian NHS. The initial investment in treatment is recouped in 4.3 years in the form of savings from disease complications avoided. Conclusion Investment in treatment of newly diagnosed patients will bring a significant reduction in disease complications, which is associated with great economic benefits. This type of action can reduce the infection rate as well as the clinical and economic disease burden of HCV in Italy. Supplementary Information The online version contains supplementary material available at 10.1007/s40258-021-00677-x.

Background & Aims COVID-19 has placed significant strain on national healthcare systems at a critical moment in the context of hepatitis elimination. Mathematical models can be used to evaluate the possible impact of programmatic delays on hepatitis disease burden. The objective of this analysis was to evaluate the incremental change in hepatitis C liver-related deaths and liver cancer, following a 3-month, 6-month, or 1-year hiatus in hepatitis elimination program progress. Methods Previously developed models were adapted for 110 countries to include a status quo or “no delay” scenario and a “1-year delay” scenario assuming significant disruption in interventions (screening, diagnosis and treatment) in the year 2020. Annual, country-level, model outcomes were extracted, and weighted averages were used to calculate regional (WHO and World Bank Income Group) and global estimates from 2020 to 2030. The incremental annual change in outcomes was calculated by subtracting the “no-delay” estimates from the “1-year delay” estimates. Results The “1-year delay” scenario resulted in 44,800 (95% UI: 43,800 – 49,300) excess hepatocellular carcinoma (HCC) cases and 72,300 (95% UI: 70,600 – 79,400) excess liver-related deaths (LRDs), relative to the “no delay” scenario globally, from 2020-2030. Most missed treatments would be in lower-middle income countries, while most excess HCC and LRDs would be among high-income countries. Conclusions The impact of COVID-19 extends beyond the direct morbidity and mortality associated with exposure and infection. In order to mitigate the impact on viral hepatitis programming and reduce excess mortality from delayed treatment, policy makers should prioritize hepatitis programs as soon as it becomes safe to do so., Graphical abstract, Highlights • With only 10 years left for hepatitis elimination, COVID-19 is impacting progress • A 1-year delay in HCV programs could cause excess HCV morbidity and mortality • A 1-year delay could cause 72,000 excess deaths from HCV • Most excess deaths would be in the lower middle income and high-income groups, COVID-19 has resulted in many hepatitis elimination programs slowing or stopping altogether. A 1-year delay in hepatitis diagnosis and treatment could result in an additional 44,800 liver cancers and 72,300 deaths from HCV globally by 2030. Countries have committed to hepatitis elimination by 2030, so attention should shift back to hepatitis programming as soon as it becomes appropriate.

Background and aims. Hepatitis C virus (HCV) elimination for Italy is an ambitious, but achievable goal. In Italy, there is political will, which aims to achieve the World Health Organization (WHO) elimination goals recognizing the need to identify undiagnosed individuals in key high-risk groups and in the general population, however there is concern regarding HCV treatment implementation in Italian Regions. Methods. A modelling analysis was conducted, using the “Italy Polaris” model, to forecast the impact of different HCV treatment rates in achieving the HCV elimination goals in Italy. The model assessed two treatment scenarios: 2018 Scenario and 2019 Scenario, using the annually HCV treatment rate in Italy. Results. Considering a high treatment rate, as assumed by the 2018 Scenario, all HCV elimination targets would be achieved. Considering the 2019 Scenario, in which a decreasing number of newly diagnosed individuals and as consequence, a decline in the number of treated patients, were assumed, only the 65% HCV mortality reduction would be an achievable goal in Italy. The other elimination targets could be achievable over 7 years later than the year 2030. Conclusions. Establishing an ad hoc fund for DAAs for each Italian Region, binding resources both for case finding, through active screening and activities for rapid linkage to care and treatment, is of paramount importance, in order to keep Italy on track to achieve the WHO elimination targets by 2030.

Objectives To conduct a cost-effectiveness analysis of two planning strategies of the second-generation direct-acting antiviral interferon-free regimens for the treatment of chronic hepatitis C virus infection. Methods A lifetime multicohort model comprised 8125 real-life patients enrolled in the PITER (Italian platform for the study of viral hepatitis) registry, implemented by the ISS (Istituto Superiore di Sanita). Two treatment planning strategies were compared: 1) policy 1—treat all patients regardless of the stage of fibrosis (F0–F4) with second-generation direct-acting antivirals and 2) policy 2—treat patients at F3/F4 stage and those who are prioritized by the scientific guidelines first, and the remaining patients when they reach the F3 stage. Clinical outcomes and costs were evaluated by using a lifetime horizon Markov model and adopting the third-party payer perspective. Health outcomes were expressed in terms of quality-adjusted life-years (QALYs). A sensitivity analysis was run to explore first- and second-order uncertainty and heterogeneity. An expected value of perfect information analysis was also conducted. Results Policy 1 exhibits an incremental cost-effectiveness ratio of €8,775/QALY gained and remains less than €30,000/QALY in 94% of realizations produced by the Monte-Carlo simulation. Such a proportion increases to 97% when adopting a threshold of €40,000/QALY gained. Conclusions Moving from the urgency criterion to evidence-based escalating strategies when prioritizing the access to new anti–hepatitis C virus treatments is a good investment in health, whose affordability should be explored through context-specific budget impact analyses.

Background Hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide. In the European Union (EU), treatment and cure of HCV with direct-acting antiviral therapies began in 2014. WHO targets are to achieve a 65% reduction in liver-related deaths, a 90% reduction of new viral hepatitis infections, and 90% of patients with viral hepatitis infections being diagnosed by 2030. This study assessed the prevalence of HCV in the EU and the level of intervention required to achieve WHO targets for HCV elimination. Methods We populated country Markov models for the 28 EU countries through a literature search of PubMed and Embase between Jan 1, 2000, and March 31, 2016, and a Delphi process to gain expert consensus and validate inputs. We aggregated country models to create a regional EU model. We used the EU model to forecast HCV disease progression (considering the effect of immigration) and developed a strategy to acehive WHO targets. We used weighted average sustained viral response rates and fibrosis restrictions to model the effect of current therapeutic guidelines. We used the EU model to forecast HCV disease progression (considering the effect of immigration) under current screening and therapeutic guidelines. Additionally, we back-calculated the total number of patients needing to be screened and treated to achieve WHO targets. Findings We estimated the number of viraemic HCV infections in 2015 to be 3 238 000 (95% uncertainty interval [UI] 2 106 000–3 795 000) of a total population of 509 868 000 in the EU, equating to a prevalence of viraemic HCV of 0·64% (95% UI 0·41–0·74). We estimated that 1 180 000 (95% UI 1 003 000–1 357 000) people were diagnosed with viraemia (36·4%), 150 000 (12 000–180 000) were treated (4·6% of the total infected population or 12·7% of the diagnosed population), 133 000 (106 000–160 000) were cured (4·1%), and 57 900 (43 900–67 300) were newly infected (1·8%) in 2015. Additionally, 30 400 (26 600–42 500) HCV-positive immigrants entered the EU. To achieve WHO targets, unrestricted treatment needs to increase from 150 000 patients in 2015 to 187 000 patients in 2025 and diagnosis needs to increase from 88 800 new cases annually in 2015 to 180 000 in 2025. Interpretation Given its advanced health-care infrastructure, the EU is uniquely poised to eliminate HCV; however, expansion of screening programmes is essential to increase treatment to achieve the WHO targets. A united effort, grounded in sound epidemiological evidence, will also be necessary. Funding Gilead Sciences.

Daclatasvir (DCV) combinated with Sofosbuvir (SOF) has shown good efficacy and safety profile for HCV patients. The aim was to evaluate the cost-effectiveness of DCV/SOF regimen versus HCV alternative treatments for patients who failed to achieve the SVR12 after a first DAA treatment from Italian perspective (PITER cohort).A Markov model of HCV chronically infected patients was used to develop two scenarios: 1) DCV+ SOF versus Ledipasvir (LDV)+ SOF in Genotype (Gt)1 and Gt4; 2) DCV+ SOF versus no retreatment option in Gt1, Gt3, and Gt4. The percentage of patients who failed the first line with SOF/Simeprevir/Ribavirin (RBV) or SOF/RBV and were retreated or not according to evidences from PITER cohort, were used to populate the model. HCV resources consumption and SVR rates were quantified using PITER data. Transition probabilities and utility rates were derived from the literature. The outcomes were expressed in terms of Quality adjusted life years (QALYs). Probabilistic sensitivity analysis (PSA) was performed considering a cost-effectiveness threshold of € 30,000/QALY.In the base-case analysis, DCV+ SOF represents a cost-effectiveness therapy with ICERs lower than the threshold. The PSA showed robust results, ICERs remain below the threshold in 94% and 99% simulations in Scenario 1 and 2, respectively.

PubMed: 29599078, 2-s2.0-85044540918, Background: The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate viral hepatitis by 2030. Although no virological cure exists for hepatitis B virus (HBV) infection, existing therapies to control viral replication and prophylaxis to minimise mother-to-child transmission make elimination of HBV feasible. We aimed to estimate the national, regional, and global prevalence of HBsAg in the general population and in the population aged 5 years in 2016, as well as coverage of prophylaxis, diagnosis, and treatment. Methods: In this modelling study, we used a Delphi process that included a literature review in PubMed and Embase, followed by interviews with experts, to quantify the historical epidemiology of HBV infection. We then used a dynamic HBV transmission and progression model to estimate the country-level and regional-level prevalence of HBsAg in 2016 and the effect of prophylaxis and treatment on disease burden. Findings: We developed models for 120 countries, 78 of which were populated with data approved by experts. Using these models, we estimated that the global prevalence of HBsAg in 2016 was 3·9% (95% uncertainty interval [UI] 3·4–4·6), corresponding to 291 992 000 (251 513 000–341 114 000) infections. Of these infections, around 29 million (10%) were diagnosed, and only 4·8 million (5%) of 94 million individuals eligible for treatment actually received antiviral therapy. Around 1·8 (1·6–2·2) million infections were in children aged 5 years, with a prevalence of 1·4% (1·2–1·6). We estimated that 87% of infants had received the three-dose HBV vaccination in the first year of life, 46% had received timely birth-dose vaccination, and 13% had received hepatitis B immunoglobulin along with the full vaccination regimen. Less than 1% of mothers with a high viral load had received antiviral therapy to reduce mother-to-child transmission. Interpretation: Our estimate of HBV prevalence in 2016 differs from previous studies, potentially because we took into account the effect of infant prophylaxis and early childhood vaccination, as well as changing prevalence over time. Although some regions are well on their way to meeting prophylaxis and prevalence targets, all regions must substantially scale-up access to diagnosis and treatment to meet the global targets. Funding: John C Martin Foundation. © 2018 Elsevier Ltd, H28-kansei-ippan-001 National Academy of Sciences, NAS Novartis Roche World Health Organization, WHO Gilead Sciences Alnylam Pharmaceuticals AbbVie Meso Scale Diagnostics, MSD British Microcirculation Society, BMS Japan Society for the Promotion of Science, JSPS: 17H03589 Ministry of Health, Labour and Welfare, MHLW Vetenskapsrådet, VR Siemens Universiteit Antwerpen OLL-683801, DR-S, IGa, SB, SMB, CE, KM, HMN, KP, KR-S, SR, JDS, and HR report grants from John C Martin Foundation, during the conduct of the study, and grants from Gilead Sciences, AbbVie, WHO, National Academy of Sciences, Intercept Pharmaceuticals, and Boehringer Ingelheim, outside the submitted work. MHN reports grants and personal fees from Bristol-Myers Squibb (BMS), Gilead Sciences, and Janssen, and personal fees from Novartis, Anylam, and Dynavax, outside the submitted work. PVD acts as chief and principal investigator for vaccine trials done on behalf of the University of Antwerp, Belgium, for which the University obtains research grants from vaccine manufacturers; speaker's fees for presentations on vaccines are paid directly to an educational fund held by the University of Antwerp, and PVD receives no personal remuneration for this work. ACA reports personal fees from Mylan Pharmaceuticals, outside the submitted work. JEA reports fees paid to his hospital for participation on the advisory boards of Gilead Sciences, ViiV Healthcare, BMS, Janssen, and AbbVie, and grants from BMS, Merck Sharp & Dohme (MSD), AbbVie, and ViiV Healthcare, outside the submitted work. TB reports grants, personal fees, and non-financial support from AbbVie and Gilead Sciences; grants and personal fees from BMS, Janssen, Roche, MSD, and Sequana Medical; and personal fees from Bayer, Vertex, Tibotec, Intercept, Sirtex, and Alexion, outside the submitted work. PB reports grants and personal fees from AbbVie, Gilead Sciences, and MSD, outside the submitted work. MBr reports personal fees from BMS, Gilead Sciences, and Janssen, and grants from BMS, outside the submitted work. HLYC reports personal fees from Gilead Sciences, BMS, AbbVie, Roche, MedImmune, and Intellia, outside the submitted work. PBC reports grants from AbbVie, Gilead Sciences, and MSD, outside the submitted work. VC reports personal fees from AbbVie, BMS, Gilead Sciences, and MSD, and grants from BMS, outside the submitted work. MCor reports personal fees from AbbVie, BMS, Boehringer Ingelheim, Biogen Idec, Falk Foundation, Gilead Sciences, Janssen, MSD, Roche Diagnostics, Roche Pharma, and Siemens, outside the submitted work. SD and PJ report personal fees and non-financial support from AbbVie and Gilead Sciences, and personal fees from MSD, outside the submitted work. MHE-S is an advisory board member for Perspectum Diagnostics, and reports grants and non-financial support from Gilead Sciences, and non-financial support from AbbVie and Quadri Pharma, outside the submitted work. RF reports grants, personal fees, and non-financial support from Roche and Gilead Sciences, and personal fees and non-financial support from BMS, outside the submitted work. GBG reports grants and personal fees from Gilead Sciences, outside the submitted work. JG-S reports grants and personal fees from Gilead Sciences, and personal fees from MSD, Abbvie, Janssen, and BMS, outside the submitted work. JGer reports grants and personal fees from AbbVie, Gilead Sciences, Janssen, MSD, BMS, and ViiV Healthcare, outside the submitted work. RG reports grants from New South Wales Ministry of Health and provided project advice regarding viral hepatitis treatment to Gilead Sciences, outside the submitted work. AHa reports unrestricted grants from AbbVie, MSD, Gilead Sciences, BMS, and Novartis, and non-financial support from Gilead Sciences, outside the submitted work; he was also on advisory boards for AbbVie, Gilead Sciences, and BMS. CH reports personal fees from AbbVie, BMS, Gilead Sciences, Janssen, and MSD, outside the submitted work. JJ reports personal fees and non-financial support from Gilead Sciences and AbbVie, and personal fees from Roche and BMS, outside the submitted work. MK reports grants from Roche, Siemens, Hologic, and Boerhinger Ingleheim, outside the submitted work. JVL reports grants and personal fees from Gilead Sciences and personal fees from Cepheid, outside the submitted work. MMan reports personal fees from Roche, BMS, GlaxoSmithKline, Aevi Genomic Medicine, ENYO Pharma, and CureVac, and grants and personal fees from Gilead Sciences and Novartis, outside the submitted work. SMau reports personal fees and non-financial support from Gilead Sciences and BMS, outside the submitted work. CM reports grants and personal fees from AbbVie, Gilead Sciences, and BMS; personal fees from MSD; and grants from Roche, outside the submitted work. BM reports grants and personal fees from Gilead Sciences and personal fees from AbbVie, MSD, BMS, Bayer, Intercept, and Sigma-Tau, during the conduct of the study. FN reports personal fees and non-financial support from Gilead Sciences, during the conduct of the study. AR reports grants and personal fees from AbbVie, Gilead, and MSD, and personal fees form BMS, Celgene, Janssen, Intercept, and Lupin, outside the submitted work. HWR reports grants and personal fees from AbbVie, BMS, Boehringer Ingelheim, ENYO Pharma, Gilead Sciences, Janssen, MSD, PRA Health Sciences, Regulus, and Roche; personal fees from Alnylam and R-Pharm; and grants from Replicor, outside the submitted work. LRR reports grants from the Center for Clinical and Translational Science and the Swedish Research Council (Ghana), during the conduct of the study. LRR also reports grants from Gilead Sciences, BTG, Ariad, and Wako, outside the submitted work, and was a consultant and advisory board member for Wako, Medscape, Axis, OncLive, Bayer, Tavec, and Grail. SDR has served as an advisory board member and speaker for Gilead Sciences, AbbVie, and MSD. OS has served as a consultant and on advisory boards for MSD; received research grants from AbbVie, BMS, MSD, Boehringer Ingelheim, R-Pharm, and Hepatera; and served as a speaker for Abbott, AbbVie, BMS, Gilead Sciences, Janssen, MSD, and R-Pharm. JFS-A reports personal fees from AbbVie and grants from Gilead Sciences and Janssen, outside the submitted work. CSa reports personal fees from Gilead Sciences and BMS, outside the submitted work. PS reports grants and personal fees from Gilead Sciences, AbbVie, and BMS, and personal fees from Intercept, outside the submitted work. CSt has consulted with and served on advisory boards for Gilead Sciences, AbbVie, and MSD. VSy reports grants and personal fees from Gilead Sciences, personal fees and non-financial support from AbbVie, and personal fees from Janssen, outside the submitted work. KT reports grants and personal fees from AbbVie, Gilead Sciences, and BMS; personal fees from MSD and Alfa Wasserman; and grants from Janssen, outside the submitted work. AJvdM reports grants and personal fees from Gilead Sciences and personal fees from AbbVie, outside the submitted work. IW reports personal fees from AbbVie, Gilead Sciences, Janssen, Marcyrl, Mylan, Onxio, and Pharco, outside the submitted work. NW reports personal fees paid to her department from AbbVie, BMS, Gilead Sciences, and MSD, outside the submitted work. VWW reports personal fees from Gilead Sciences, BMS, and MSD, outside the submitted work. M-FY was a speaker or advisory board member for AbbVie, BMS, Gilead Sciences, Roche, GlaxoSmithKline, Fujirebio, Biocartis, and MSD, outside the submitted work. SZ reports consultancy and lecture fees from AbbVie, Gilead Sciences, and MSD, and consultancy fees from Intercept, outside the submitted work. All other authors declare no competing interests., This study was funded by the John C Martin Foundation through the Polaris Observatory. We thank the Research on Hepatitis group (H28-kansei-ippan-001 and H25-kanen-ippan-010; led by JT), funded by the Ministry of Health, Labour and Welfare of Japan, for their provision of country-level data for Japan, and Örebro County Council for providing ALF grants (OLL-683801) to A-SD, which allowed collection of country-level data for Sweden.

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.

WOS: 000426979400014, PubMed ID: 28404132, Background The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become a reality with the recent launch of direct acting antiviral therapies. Reliable disease burden estimates are required for national strategies. This analysis estimates the global prevalence of viraemic HCV at the end of 2015, an update of-and expansion on-the 2014 analysis, which reported 80 million (95% CI 64-103) viraemic infections in 2013. Methods We developed country-level disease burden models following a systematic review of HCV prevalence (number of studies, n=6754) and genotype (n=11 342) studies published after 2013. A Delphi process was used to gain country expert consensus and validate inputs. Published estimates alone were used for countries where expert panel meetings could not be scheduled. Global prevalence was estimated using regional averages for countries without data. Findings Models were built for 100 countries, 59 of which were approved by country experts, with the remaining 41 estimated using published data alone. The remaining countries had insufficient data to create a model. The global prevalence of viraemic HCV is estimated to be 1.0% (95% uncertainty interval 0.8-1.1) in 2015, corresponding to 71.1 million (62.5-79.4) viraemic infections. Genotypes 1 and 3 were the most common cause of infections (44% and 25%, respectively). Interpretation The global estimate of viraemic infections is lower than previous estimates, largely due to more recent (lower) prevalence estimates in Africa. Additionally, increased mortality due to liver-related causes and an ageing population may have contributed to a reduction in infections., John C Martin Foundation, John C Martin Foundation.

Background: Few data are available on the virological and clinical outcomes of advanced liver disease patients retreated after first-line DAA failure. Aim: To evaluate DAA failure incidence and the retreatment clinical impact in patients treated in the advanced liver disease stage. Methods: Data on HCV genotype, liver disease severity, and first and second line DAA regimens were prospectively collected in consecutive patients who reached the 12-week post-treatment and retreatment evaluations from January 2015 to December 2016 in 23 of the PITER network centers. Results: Among 3,830 patients with advanced fibrosis (F3) or cirrhosis, 139 (3.6%) failed to achieve SVR. Genotype 3, bilirubin levels >1.5mg/dl, platelet count