The current and future burden of hepatitis B in Switzerland: a modelling study.

BACKGROUND AND AIMS: Chronic hepatitis B infection (defined as sustained detection of hepatitis B virus [HBV] surface antigen [HBsAg] protein in serum) is a leading cause of cirrhosis, hepatocellular carcinoma and liver-related deaths. A situation analysis carried out by the Swiss Federal Office of Public Health estimated the HBsAg prevalence in Switzerland to be 0.53% (95% CI: 0.32-0.89%) in 2015 (~44,000 cases). A lower prevalence of chronic HBV in the younger generation and the adoption of universal coverage in the first year of life are expected to decrease the burden of HBV; however, a number of people in key populations (including migrants) remain undiagnosed and untreated, and infected individuals remain at risk of progressing to cirrhosis, hepatocellular carcinoma and death. Our primary objective was to examine the current and estimate the future disease burden of HBV in Switzerland and the impact of migration. The secondary objective was to estimate the impact of changing future treatment numbers. METHODS: A modelling study was performed using an existing, validated model (PRoGReSs Model) applied to the Swiss context. Model inputs were selected through a literature search and expert consensus. Population data from the Federal Statistical Office were used alongside prevalence data from the Polaris Observatory to estimate the number of HBV infections among people born abroad. The PRoGReSs Model was populated with and calibrated to the available data and what-if scenarios were developed to explore the impact of intervention on the future burden of disease. A Monte Carlo simulation was used to estimate 95% uncertainty intervals (95% UIs). RESULTS: In 2020, there were an estimated 50,100 (95% UI: 47,500-55,000) HBsAg+ cases among people born abroad. Among people born in Switzerland, there were approximately 62,700 (UI: 58,900-68,400) total HBV infections (0.72% [UI: 0.68-0.79%] prevalence). Prevalence among infants and children under the age of 5 were both <0.1%. By 2030, prevalence of HBV is expected to decrease, although morbidity and mortality will increase. Increasing diagnosis (90%) and treatment (80% of those eligible) to meet the global health sector strategy on viral hepatitis programme targets could prevent 120 cases of hepatocellular carcinoma and 120 liver-related deaths. CONCLUSIONS: Thanks to the historical vaccination programmes and the continued rollout of universal 3-dose coverage in the first year of life, Switzerland is expected to exceed the global health sector strategy targets for the reduction of incidence. While overall prevalence is decreasing, the current diagnosis and treatment levels remain below global health sector strategy targets.

The impact of immigration on hepatitis B burden in the United States: a modelling study.

Background: The 2016 World Health Assembly endorsed the elimination of hepatitis B virus (HBV) infections by 2030. However, the HBV prevalence in Western countries, where the historical prevalence is low and highly impacted by immigration trends, remains uncertain making planning difficult. We aimed to develop a more accurate estimate of HBV prevalence and identify key immigrant populations that need to be screened, vaccinated, and treated to achieve the elimination targets. Methods: US immigration data from 1900 forward and country-specific modeled prevalence by age and sex were used to estimate immigrated HBV infections entering the US, new infections in the US, mortality (all-cause and liver-related), and disease burden through 2030. Findings: Using a dynamic Markov model, we estimated 1.8 million (95% uncertainty interval: 1.3-2.6 million) HBV infections in 2020 in all ages, higher than the NHANES national serosurvey. Infections between ages 30-74 accounted for 82% of all cases. Furthermore, HBV infections were concentrated among immigrants. New decompensated cirrhosis, hepatocellular carcinoma, and liver related deaths are expected to increase by 20%, 31% and 25% respectively from 2019 to 2030 at current diagnosis and treatment rate. Interpretation: National serosurveys can underestimate total infections due to under-sampling in immigrant populations. To meet the WHO elimination targets, culturally appropriate screening and linkage to care programs in the immigrant populations are needed in the US. In their absence, there will be significant increases in the burden of HBV and the US will fail to meet the elimination targets by 2030. Funding: This analysis was funded by a research grant from Gilead Sciences (IN-US-988-5786) and made possible by grants from John C Martin Foundation (2019-G024), ZeShan Foundation (2021-0101-1-CDA-HEP-10), and EndHep2030 who supported country analyses.

Evidence for Benefits of Early Treatment Initiation for Chronic Hepatitis B.

Chronic hepatitis B (CHB) is the most common cause of hepatocellular carcinoma (HCC) worldwide. Antiviral treatment reduces the risk of HCC and mortality; nonetheless, globally in 2019, only 2.2% of CHB patients received treatment. Current international CHB guidelines recommend antiviral treatment only in subsets of patients with clear evidence of liver damage. This contrasts with hepatitis C or HIV where early treatment is recommended in all infected patients, regardless of end-organ damage. This narrative review aims to provide an overview of data on the early initiation of antiviral treatment and its related potential economic impact. Literature searches were performed using PubMed and abstracts from international liver congresses (2019-2021). Data on risk of disease progression and HCC and the impact of antiviral treatment in currently ineligible patients were summarized. Cost-effectiveness data on early antiviral treatment initiation were also collated. Accumulating molecular, clinical, and economic data suggest that early initiation of antiviral treatment could save many lives through HCC prevention in a highly cost-effective manner. In light of these data, we consider several alternative expanded treatment strategies that might further a simplified 'treatment as prevention' approach.

Hepatitis D double reflex testing of all hepatitis B carriers in low-HBV- and high-HBV/HDV-prevalence countries.

Hepatitis D virus (HDV) infection occurs as a coinfection with hepatitis B and increases the risk of hepatocellular carcinoma, decompensated cirrhosis, and mortality compared to hepatitis B virus (HBV) monoinfection. Reliable estimates of the prevalence of HDV infection and disease burden are essential to formulate strategies to find coinfected individuals more effectively and efficiently. The global prevalence of HBV infections was estimated to be 262,240,000 in 2021. Only 1,994,000 of the HBV infections were newly diagnosed in 2021, with more than half of the new diagnoses made in China. Our initial estimates indicated a much lower prevalence of HDV antibody (anti-HDV) and HDV RNA positivity than previously reported in published studies. Accurate estimates of HDV prevalence are needed. The most effective method to generate estimates of the prevalence of anti-HDV and HDV RNA positivity and to find undiagnosed individuals at the national level is to implement double reflex testing. This requires anti-HDV testing of all hepatitis B surface antigen-positive individuals and HDV RNA testing of all anti-HDV-positive individuals. This strategy is manageable for healthcare systems since the number of newly diagnosed HBV cases is low. At the global level, a comprehensive HDV screening strategy would require only 1,994,000 HDV antibody tests and less than 89,000 HDV PCR tests. Double reflex testing is the preferred strategy in countries with a low prevalence of HBV and those with a high prevalence of both HBV and HDV. For example, in the European Union and North America only 35,000 and 22,000 cases, respectively, will require anti-HDV testing annually.

Hepatitis C prevalence and elimination planning in Pakistan, a bottom-up approach accounting for provincial variation.

In Pakistan, substantial changes to hepatitis C virus (HCV) programming and treatment have occurred since the 2008 nationwide serosurvey estimated a 4.8% anti-HCV prevalence. In the absence of an updated national study, this analysis uses provincial data to estimate a national prevalence and the interventions needed to achieve elimination. Using a Delphi process, epidemiologic HCV data for the four provinces of Pakistan (accounting for 97% of the population) were reviewed with 21 subject-matter experts in Pakistan. Province-level estimates were inputted into a mathematical model to estimate the national HCV disease burden in the absence of intervention (Base), and if the World Health Organization (WHO) elimination targets are achieved by 2030 (80% reduction in new infections, 90% diagnosis coverage, 80% treatment coverage, and 65% reduction in mortality: WHO Elimination). An estimated 9,746,000 (7,573,000-10,006,000) Pakistanis were living with viraemic HCV as of January 1, 2021; a viraemic prevalence of 4.3% (3.3-4.4). WHO Elimination would require an annual average of 18.8 million screens, 1.1 million treatments, and 46,700 new infections prevented anually between 2022 and 2030. Elimination would reduce total infections by 7,045,000, save 152,000 lives and prevent 104,000 incident cases of hepatocellular carcinoma from 2015 to 2030. Blood surveys, programmatic data, and expert panel input uncovered more HCV infections and lower treatment numbers in the provinces than estimated using national extrapolations, demonstrating the benefits of a bottom-up approach. Screening and treatment must increase 20 times and 5 times, respectively, to curb the HCV epidemic in Pakistan and achieve elimination by 2030.

Modeling HCV elimination recovery following the COVID-19 pandemic in the United States: Pathways to regain progress.

BACKGROUND: As of 2019, the United States (US) was not on track to achieve targets for elimination, due to increasing incidence and treatment barriers. In 2020, the COVID-19 pandemic disrupted HCV services globally and in the US. As healthcare services normalize, there is an urgent need to reassess progress and evaluate scenarios that restore a pathway toward HCV elimination. METHODS: We updated a validated Markov model to estimate HCV-related morbidity and mortality in the US. Five scenarios were developed to bookend possible HCV outcomes in the wake of the pandemic. These included 1) return to pre-COVID-19 treatment forecasts; 2) achieve elimination targets through treatment and harm reduction; 3) long-term treatment disruptions; 4/5) achieve elimination targets through increased treatment without increased harm reduction, starting in either 2022 or 2025. FINDINGS: From 2014-2019, more than 1.2 million patients were treated for HCV in the US. Elimination targets in 2030 could be achieved in the US by treating an additional 3.2-3.3 million patients from 2020 to 2030, or by preventing new infections through expanded harm reduction programs and treating up to 2.7 million patients. Intervention scenarios could prevent over 30,000 HCC cases and over 29,000 liver-related deaths. INTERPRETATION: The US has made strides toward HCV elimination, but gains could be lost in the wake of the pandemic. However, it is still possible to avert nearly 30,000 deaths through increased harm reduction and increased treatment rates. This requires a coordinated effort from the entire HCV community.

Securing wider EU commitment to the elimination of hepatitis C virus.

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.

Impact of expanding hepatitis B treatment guidelines: A modelling and economic impact analysis.

BACKGROUND: Antiviral treatment in patients with chronic hepatitis B (CHB) may decrease the risk of hepatocellular carcinoma (HCC) and death. However, only 2.2% of CHB patients receive antiviral treatment globally. The complexity and strictness of the current clinical practice guidelines may limit expanding the treatment coverage for CHB. AIMS: To examine the impact of expanding treatment criteria on future disease burden in Korea, a hepatitis B virus (HBV) endemic country with high diagnostic rates. MATERIALS: Dynamic country-level data were used to estimate the HCC incidence, overall mortality and economic impact of three incremental scenarios compared to the base case in Korea through 2035. RESULTS: In 2020, 1,409,000 CHB cases were estimated, with the majority born before 1995. All scenarios assumed treating 70% of eligible individuals. The first scenario removed viral load restrictions in cirrhotic patients, which would avert 13,000 cases of HCC and save 11,800 lives. The second scenario, lowering the alanine aminotransferase (ALT) level restriction to the upper limit of the normal in non-cirrhotic patients, would avert 26,700 cases of HCC and save 23,300 lives. The last scenario removed the restriction by ALT and HBeAg in treating non-cirrhotic individuals with a viral load of ≥2000 IU/ml, which would avert 43,300 cases of HCC and save 37,000 lives. All scenarios were highly cost-effective. CONCLUSIONS: Simplifying and expanding treatment eligibility for CHB would save many lives and be highly cost-effective when combined with high diagnostic rates. These dynamic country-level data may provide new insights for their global application.

Updated epidemiology of hepatitis C virus infections and implications for hepatitis C virus elimination in Germany.

In 2014, an analysis was conducted to evaluate the hepatitis C virus (HCV) epidemiology and disease burden in Germany. Since then, there have been considerable developments in HCV management such as the implementation of direct acting antivirals. The aim of this analysis was to assess the recent data available for Germany, establish an updated 2020 HCV prevalence and cascade of care and evaluate the impact of what-if scenarios on the future burden of disease using modelling analysis. A dynamic Markov model was used to forecast the HCV disease burden in Germany. Model inputs were retrieved through literature review, unpublished sources and expert input. Next, three "what-if" scenarios were developed to evaluate the status quo, COVID-19 pandemic, and steps needed to achieve the WHO targets for elimination. At the beginning of 2020, there were 189,000 (95% UI: 76,700-295,000) viremic infections in Germany, a decline of more than 85,000 viremic infections since 2012. Annual treatment starts went down since 2015. Compared with 2019, the COVID-19 pandemic resulted in a further 11% decline in 2020. If this continues for two years, it could result in 110 excess HCC cases and 200 excess liver related deaths by 2030. To achieve the WHO targets, 81,200 people need to be diagnosed, with 118,600 initiated on treatment by 2030. This could also avert 1,020 deaths and 720 HCC cases between 2021 and 2030. Germany has made strides towards HCV elimination, but more efforts are needed to achieve the WHO targets by 2030.

Epidemiology, Natural History, and Outcomes of Primary Sclerosing Cholangitis: A Systematic Review of Population-based Studies.

BACKGROUND & AIMS: The aim of this study was to quantify the global epidemiology of primary sclerosing cholangitis (PSC), alongside the incidence of liver transplantation, cancer, and death, through robust systematic review of population-based data. METHODS: We searched MEDLINE and EMBASE up to and including June 30, 2020 to identify population-based studies reporting the incidence and/or prevalence of PSC. Studies that did not report original data, or of exclusively pediatric-onset disease (diagnosis age <16 years) or exclusively PSC-associated with inflammatory bowel disease were excluded. RESULTS: Of 4922 published studies, 17 fulfilled inclusion criteria; 16 documenting incidence and 14 prevalence. The highest reported incidence of PSC was reported in Northern Europe (Finland, 1.58 and Norway, 1.3 per-100,000 population, respectively) and North America (Minnesota, 1.47); with the lowest being observed across the Mediterranean Basin (Italy, 0.1). Prevalence ranged from 31.7 in Finland and 23.99 in Minnesota, to 1.33 in Singapore and 0.0 in Alaska. Of studies reporting temporal occurrence, an increase in disease incidence was observed across North America and Northern Europe (4 studies), alongside an increase in prevalence over time (4 studies). The incidence and risks for clinical outcomes were presented by 9 of the included studies. Median transplant-free survival ranged from 9.7 (United States) to 20.6 years (Netherlands), with standardized mortality ratios of 2.5 and 4.2 compared with the control population. The standardized incidence of cholangiocarcinoma ranged from 235 (Finland) to 398 (Netherlands). CONCLUSIONS: Estimates of PSC incidence and prevalence vary, with most studies conducted in North America and Western Europe; the latter showing a steady increase in disease occurrence over time. Further research is needed to understand changes in disease epidemiology, including etiological drivers, the implications of rising case burden on health care policy, and better appreciation of PSC in the developing world.

Progress towards achieving viral hepatitis B and C elimination in the Asia and Pacific region: Results from modelling and global reporting.

In 2016, Asia and Pacific countries endorsed action plans for reaching viral hepatitis elimination targets set in the Global Health Sector Strategy (GHSS) for Viral Hepatitis 2016-2021. We examine the region's progress by modelling disease burden and constructing the cascade of care. Between 2015 and 2020, chronic HBV prevalence declined from 4.69% to 4.30%, and HCV prevalence declined from 0.64% to 0.58%. The region achieved the 2020 target of 30% incidence reduction for HBV, whereas HCV incidence declined by 6%. Hepatocellular carcinoma incidence for HBV and HCV increased by 9% and 7%, respectively. Liver-related deaths from HBV rose by 8%, and mortality attributable to HCV plateaued. Large testing and treatment gaps remained in 2019: only 13% of chronic HBV infections were diagnosed and 25% treated; 21% of chronic HCV infection were diagnosed and 11% treated. Viral hepatitis must become national priority with adequate funding to reach elimination goals by 2030.

Lives saved with vaccination for 10 pathogens across 112 countries in a pre-COVID-19 world.

Background: Vaccination is one of the most effective public health interventions. We investigate the impact of vaccination activities for Haemophilus influenzae type b, hepatitis B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, rotavirus, rubella, Streptococcus pneumoniae, and yellow fever over the years 2000-2030 across 112 countries. Methods: Twenty-one mathematical models estimated disease burden using standardised demographic and immunisation data. Impact was attributed to the year of vaccination through vaccine-activity-stratified impact ratios. Results: We estimate 97 (95%CrI[80, 120]) million deaths would be averted due to vaccination activities over 2000-2030, with 50 (95%CrI[41, 62]) million deaths averted by activities between 2000 and 2019. For children under-5 born between 2000 and 2030, we estimate 52 (95%CrI[41, 69]) million more deaths would occur over their lifetimes without vaccination against these diseases. Conclusions: This study represents the largest assessment of vaccine impact before COVID-19-related disruptions and provides motivation for sustaining and improving global vaccination coverage in the future. Funding: VIMC is jointly funded by Gavi, the Vaccine Alliance, and the Bill and Melinda Gates Foundation (BMGF) (BMGF grant number: OPP1157270 / INV-009125). Funding from Gavi is channelled via VIMC to the Consortium's modelling groups (VIMC-funded institutions represented in this paper: Imperial College London, London School of Hygiene and Tropical Medicine, Oxford University Clinical Research Unit, Public Health England, Johns Hopkins University, The Pennsylvania State University, Center for Disease Analysis Foundation, Kaiser Permanente Washington, University of Cambridge, University of Notre Dame, Harvard University, Conservatoire National des Arts et Métiers, Emory University, National University of Singapore). Funding from BMGF was used for salaries of the Consortium secretariat (authors represented here: TBH, MJ, XL, SE-L, JT, KW, NMF, KAMG); and channelled via VIMC for travel and subsistence costs of all Consortium members (all authors). We also acknowledge funding from the UK Medical Research Council and Department for International Development, which supported aspects of VIMC's work (MRC grant number: MR/R015600/1).JHH acknowledges funding from National Science Foundation Graduate Research Fellowship; Richard and Peggy Notebaert Premier Fellowship from the University of Notre Dame. BAL acknowledges funding from NIH/NIGMS (grant number R01 GM124280) and NIH/NIAID (grant number R01 AI112970). The Lives Saved Tool (LiST) receives funding support from the Bill and Melinda Gates Foundation.This paper was compiled by all coauthors, including two coauthors from Gavi. Other funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Estimating the health impact of vaccination against ten pathogens in 98 low-income and middle-income countries from 2000 to 2030: a modelling study.

BACKGROUND: The past two decades have seen expansion of childhood vaccination programmes in low-income and middle-income countries (LMICs). We quantify the health impact of these programmes by estimating the deaths and disability-adjusted life-years (DALYs) averted by vaccination against ten pathogens in 98 LMICs between 2000 and 2030. METHODS: 16 independent research groups provided model-based disease burden estimates under a range of vaccination coverage scenarios for ten pathogens: hepatitis B virus, Haemophilus influenzae type B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, Streptococcus pneumoniae, rotavirus, rubella, and yellow fever. Using standardised demographic data and vaccine coverage, the impact of vaccination programmes was determined by comparing model estimates from a no-vaccination counterfactual scenario with those from a reported and projected vaccination scenario. We present deaths and DALYs averted between 2000 and 2030 by calendar year and by annual birth cohort. FINDINGS: We estimate that vaccination of the ten selected pathogens will have averted 69 million (95% credible interval 52-88) deaths between 2000 and 2030, of which 37 million (30-48) were averted between 2000 and 2019. From 2000 to 2019, this represents a 45% (36-58) reduction in deaths compared with the counterfactual scenario of no vaccination. Most of this impact is concentrated in a reduction in mortality among children younger than 5 years (57% reduction [52-66]), most notably from measles. Over the lifetime of birth cohorts born between 2000 and 2030, we predict that 120 million (93-150) deaths will be averted by vaccination, of which 58 million (39-76) are due to measles vaccination and 38 million (25-52) are due to hepatitis B vaccination. We estimate that increases in vaccine coverage and introductions of additional vaccines will result in a 72% (59-81) reduction in lifetime mortality in the 2019 birth cohort. INTERPRETATION: Increases in vaccine coverage and the introduction of new vaccines into LMICs have had a major impact in reducing mortality. These public health gains are predicted to increase in coming decades if progress in increasing coverage is sustained. FUNDING: Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation.

Impact of COVID-19 on global HCV elimination efforts.

BACKGROUND & AIMS: Coronavirus disease 2019 (COVID-19) has placed a 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 HCV liver-related deaths and liver cancer, following a 3-month, 6-month, or 1-year hiatus in hepatitis elimination programs. 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% uncertainty interval [UI]: 43,800-49,300) excess hepatocellular carcinoma cases and 72,300 (95% UI: 70,600-79,400) excess liver-related deaths, relative to the 'no-delay' scenario globally, from 2020 to 2030. Most missed treatments would be in lower-middle income countries, whereas most excess hepatocellular carcinoma and liver-related deaths would be among high-income countries. CONCLUSIONS: The impact of COVID-19 extends beyond the direct morbidity and mortality associated with exposure and infection. 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. LAY SUMMARY: 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 to do so.

A tool to measure the economic impact of Hepatitis B elimination: A case study in Saudi Arabia.

BACKGROUND: No virologic cure exists for hepatitis B virus (HBV) infection, and existing therapies are designed to control viral replication. We aimed to estimate the national prevalence of HBsAg in 2017 and study the impact of an enhanced diagnosis rate and universal treatment administration on HBV-related outcomes in Saudi Arabia. MATERIALS AND METHODS: A dynamic transmission and disease burden model was developed to estimate the future economic burden of HBV infection. The infected population was tracked by age and gender-defined cohorts; direct costs (healthcare, screening, diagnostics and treatment) and indirect costs (disability-adjusted life years and the value of a statistical life year) were calculated. The impact of two intervention scenarios (Achieve WHO Targets: diagnose 90% of infections and treat 80% of high viral load patients by 2030; and Diagnose and Treat All: diagnose and treat all infected patients by 2022) were compared against the Base Case scenario (no policy action), with near-universal vaccination coverage rates held constant. A sensitivity analysis of future treatment cost was also conducted. RESULTS: In 2017, HBsAg prevalence was estimated at 1.7%, corresponding to 574,000 infections. The same year, there was an estimated incidence of 490 cases of decompensated cirrhosis, 1500 cases of hepatocellular carcinoma (HCC) and 1740 liver-related deaths (LRD). HBsAg prevalence was 0.1% among 5-year-olds and <0.1% among infants. Disease burden outcomes by 2030, as compared with 2015, were as follows - Base Case: LRDs and HCC incidence were projected to increase by 70%. WHO Targets: A 30-35% decline in both HCC incidence and LRDs. Diagnose and Treat All: A 50-55% decline in HCC incidence and LRDs. In all scenarios, HBsAg prevalence among infants and 5-year-olds declined to <0.1% with the Diagnose and Treat all scenario resulting in a prevalence approaching zero in this age group. Annual direct costs are projected to increase and peak by 2022 in both intervention scenarios due to expansion of treatment and diagnostics. However, these are offset by the reduction of indirect economic costs, starting immediately in the WHO Targets scenario and by 2023 in the strategy to diagnose and treat all. Achieving WHO Targets is estimated to achieve a positive return on investment (ROI) by 2021 when examining direct costs and indirect economic losses at a treatment price of $2700 USD per patient yearly. Diagnosing and treating all patients, however, would require at least a 50% reduction in the unit cost of treatment to achieve a positive ROI by 2029. CONCLUSIONS: Increased diagnosis and treatment rates of HBV would lead to substantial declines in HCC and LRD. This effect would be dramatically enhanced by administering treatment to all HBV cases regardless of viral load and estimated to be highly cost-effective if treatment prices can be substantially reduced.

Tailored screening and dedicated funding for direct acting antiviral drugs: how to keep Italy on the road to hepatitis C virus elimination?

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.

Burden of nonalcoholic fatty liver disease in Canada, 2019-2030: a modelling study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) account for a growing proportion of liver disease cases, and there is a need to better understand future disease burden. We used a modelling framework to forecast the burden of disease of NAFLD and NASH for Canada. METHODS: We used a Markov model to forecast fibrosis progression from stage F0 (no fibrosis) to stage F4 (compensated cirrhosis) and subsequent progression to decompensated cirrhosis, hepatocellular carcinoma, liver transplantation and liver-related death among Canadians with NAFLD from 2019 to 2030. We used historical trends for obesity prevalence among adults to estimate longitudinal changes in the number of incident NAFLD cases. RESULTS: The model projected that the number of NAFLD cases would increase by 20% between 2019 and 2030, from an estimated 7 757 000 cases to 9 305 000 cases. Increases in advanced fibrosis cases were relatively greater, as the number of model-estimated prevalent stage F3 cases would increase by 65%, to 357 000, and that of prevalent stage F4 cases would increase by 95%, to 195 000. Estimated incident cases of hepatocellular carcinoma and decompensated cirrhosis would increase by up to 95%, and the number of annual NAFLD-related deaths would double, to 5600. INTERPRETATION: Increasing rates of obesity translate into increasing NAFLD-related cases of cirrhosis and hepatocellular carcinoma and related mortality. Prevention efforts should be aimed at reducing the incidence of NAFLD and slowing fibrosis progression among those already affected.

Assessment of Treatment Strategies to Achieve Hepatitis C Elimination in Canada Using a Validated Model.

Importance: Achievement of the World Health Organization (WHO) target of eliminating hepatitis C virus (HCV) by 2030 will require an increase in key services, including harm reduction, HCV screening, and HCV treatment initiatives in member countries. These data are not available for Canada but are important for informing a national HCV elimination strategy. Objective: To use a decision analytical model to explore the association of different treatment strategies with HCV epidemiology and HCV-associated mortality in Canada and to assess the levels of service increase needed to meet the WHO elimination targets by 2030. Design, Setting, and Participants: Study participants in this decision analytical model included individuals with hepatitis C virus infection in Canada. Five HCV treatment scenarios (optimistic, very aggressive, aggressive, gradual decrease, and rapid decrease) were applied using a previously validated Markov-type mathematical model. The optimistic and very aggressive treatment scenarios modeled a sustained annual treatment of 10 200 persons and 14 000 persons, respectively, from 2018 to 2030. The aggressive, gradual decrease, and rapid decrease scenarios assessed decreases in treatment uptake from 14 000 persons to 10 000 persons per year, 12 000 persons to 8500 persons per year, and 12 000 persons to 4500 persons per year, respectively, between 2018 and 2030. Main Outcomes and Measures: Hepatitis C virus prevalence and HCV-associated health outcomes were assessed for each of the 5 treatment scenarios with the goal of identifying strategies to achieve HCV elimination by 2030. Results: An estimated mean 180 142 persons (95% CI, 122 786-196 862 persons) in Canada had chronic HCV infection at the end of 2017. The optimistic and gradual decrease scenarios estimated a decrease in HCV prevalence from 180 142 persons to 37 246 persons and 37 721 persons, respectively, by 2030. Relative to 2015, this decrease in HCV prevalence was associated with 74%, 69%, and 69% reductions in the prevalence of decompensated cirrhosis, hepatocellular carcinoma, and liver-associated mortality, respectively, leading to HCV elimination by 2030. More aggressive treatment uptake (very aggressive scenario) could result in goal achievement up to 3 years earlier than 2030, although a rapid decrease in the initiation of treatment (rapid decrease scenario) would preclude Canada from reaching the HCV elimination goal by 2030. Conclusions and Relevance: The study findings suggest that Canada could meet the WHO goals for HCV elimination by 2030 by sustaining the current national HCV treatment rate during the next decade. This target will not be achieved if treatment uptake is allowed to decrease rapidly.

Global Epidemiology of Viral Hepatitis.

Viral hepatitis (A, B, C, D, and E) is the leading cause of inflammation of liver tissue (hepatitis). The disease burden associated with hepatitis A and E occurs shortly after infection; it is more severe among adults. With hepatitis A and E, the number of incident cases (new acute infections) is important from a public health perspective. Long-term hepatitis has been shown to cause cirrhosis and hepatocellular carcinoma in patients. The disease burden associated with hepatitis B, C, and D appears 10 to 20 years after infection. Thus, the prevalence of these infections is important from a public health perspective.