Enhancing interventions for prevention of mother-to-child- transmission of hepatitis B virus.

Prevention of mother-to-child transmission of hepatitis B virus (HBV) infection is a cornerstone of efforts to support progress towards elimination of viral hepatitis. Current guidelines recommend maternal screening, antiviral therapy during the third trimester of high-risk pregnancies, universal and timely HBV birth dose vaccination, and post-exposure prophylaxis with hepatitis B immunoglobulin for selected neonates. However, serological and molecular diagnostic testing, treatment and HBV vaccination are not consistently deployed, particularly in many high endemicity settings, and models predict that global targets for reduction in paediatric incidence will not be met by 2030. In this article, we briefly summarise the evidence for current practice and use this as a basis to discuss areas in which prevention of mother-to-child transmission can potentially be enhanced. By reducing health inequities, enhancing pragmatic use of resources, filling data gaps, developing advocacy and education, and seeking consistent investment from multilateral agencies, significant advances can be made to further reduce vertical transmission events, with wide health, societal and economic benefits.

Cost-effectiveness of treating all hepatitis B-positive individuals in the United States.

Chronic hepatitis B virus (HBV) infection is a leading cause of liver disease and related mortality globally. However, most of the infected individuals in the United States remain undiagnosed and untreated. There is a need to understand more completely the economic and disease burden impact of removing treatment restrictions and increasing diagnosis and treatment. The PRoGReSs model, a dynamic HBV model that tracks the infected population by year, disease stage, and gender, was used to quantify the disease and economic burden of chronic HBV infection in the United States from 2020 to 2050 based on four scenarios: a status quo (base) scenario and three treat-all scenarios, in which screening, diagnosis, and treatment were maximized at different annual treatment price levels of $5382, $2000 and $750. Compared to the base scenario, the treat-all scenarios would avert 71,100 acute and 11,100 chronic incident cases of HBV, and 169,000 liver-related deaths from 2020 to 2050. At an annual treatment cost of $2000, treating all HBV infections would be highly cost-effective, and at $750 would be cost saving and would achieve a positive return on investment before 2050. Maximizing the diagnosed and treated HBV population in the United States would avert a significant number of cases of advanced liver disease and related mortality. Such interventions can also be cost-effective compared to the status quo strategy, and cost saving at a treatment price threshold of $750 annually, above the current lowest annual treatment cost of $362.

Impacts of the Egyptian national screening and treatment programme for viral hepatitis C: A cost-effectiveness model.

BACKGROUND & AIMS: Egypt used to have one of the highest prevalences of HCV infection worldwide. The Egyptian Ministry of Health launched a national campaign for the detection and management of HCV to reduce its burden. This study aims to carry out a cost-effectiveness analysis to evaluate the costs and benefits of the Egyptian national screening and treatment programme. METHODS: A disease burden and economic impact model was populated with the Egyptian national screening and treatment programme data to assess direct medical costs, health effects measured in disability-adjusted life years and the incremental cost-effectiveness ratio. The scenario was compared to a historical base case, which assumed that no programme had been conducted. RESULTS: Total number of viremic cases is expected to decrease in 2030 by 86% under the national screening and treatment programme, versus by 41% under the historical base case. Annual discounted direct medical costs are expected to decrease from $178 million in 2018 to $81 million by 2030 under the historical base case, while annual direct medical costs are estimated to have peaked in 2019 at $312 million before declining to $55 million by 2030 under the national screening and treatment programme. Under the programme, annual disability-adjusted life years are expected to decline to 127 647 by 2030, leading to 883 333 cumulative disability-adjusted life years averted over 2018-2030. CONCLUSIONS: The national screening and treatment programme is highly cost-effective by the year 2021, cost-saving by 2029 and expected to save about $35 million in direct costs and $4705 million in indirect costs by 2030.

Cost-effectiveness and economic investment to eliminate chronic hepatitis C in Mexico.

In July 2020, the Mexican Government initiated the National Program for Elimination of Hepatitis C (HCV) under a procurement agreement, securing universal, free access to HCV screening, diagnosis and treatment for 2020-2022. This analysis quantifies the clinical and economic burden of HCV (MXN) under a continuation (or end) to the agreement. A modelling and Delphi approach was used to evaluate the disease burden (2020-2030) and economic impact (2020-2035) of the Historical Base compared to Elimination, assuming the agreement continues (Elimination-Agreement to 2035) or terminates (Elimination-Agreement to 2022). We estimated cumulative costs and the per-patient treatment expenditure needed to achieve net-zero cost (the difference in cumulative costs between the scenario and the base). Elimination is defined as a 90% reduction in new infections, 90% diagnosis coverage, 80% treatment coverage and 65% reduction in mortality by 2030. A viraemic prevalence of 0.55% (0.50-0.60) was estimated on 1st January 2021, corresponding to 745,000 (95% CI 677,000-812,000) viraemic infections in Mexico. The Elimination-Agreement to 2035 would achieve net-zero cost by 2023 and accrue 31.2 billion in cumulative costs. Cumulative costs under the Elimination-Agreement to 2022 are estimated at 74.2 billion. Under Elimination-Agreement to 2022, the per-patient treatment price must decrease to 11,000 to achieve net-zero cost by 2035. The Mexican Government could extend the agreement through 2035 or reduce the cost of HCV treatment to 11,000 to achieve HCV elimination at net-zero cost.

Cost-effectiveness modelling of birth and infant dose vaccination against hepatitis B virus in Ontario from 2020 to 2050.

BACKGROUND: The World Health Organization recommends universal birth dose vaccination for hepatitis B virus (HBV), yet only 3 provinces and territories in Canada provide birth dose vaccination, and Canadian-born children in Ontario are acquiring HBV before adolescent vaccination. We sought to determine whether birth and/or infant HBV vaccination is cost-effective. METHODS: We used a dynamic HBV model that incorporates population by year, disease stage, sex and the influence of immigration to quantify the disease and economic burden of chronic HBV infection in Ontario from 2020 to 2050. We compared 4 vaccination scenarios, which included a birth dose vaccine and variations of the 2 subsequent doses (either alone or as a part of the hexavalent vaccine) and a hexavalent-only strategy in infancy with the current adolescent vaccination strategy. Our costing estimates were based on values from 2020. RESULTS: All 4 infant vaccination approaches prevented an additional 550-560 acute and 160 chronic pediatric HBV infections from 2020 to 2050 compared with adolescent vaccination. Whereas birth dose could be cost-effective, incorporating vaccination into a hexavalent vaccine was cost saving. By 2050, the hexavalent approach led to $428 000 in cost savings per disability-adjusted life years averted. INTERPRETATION: At the current prevalence in Ontario, a switch to birth dose or infant dose will be cost-effective or even cost saving. Introducing any form of infant HBV immunization in Ontario will prevent acute and chronic pediatric HBV infections.

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.

The Payer License Agreement, or "Netflix model," for hepatitis C virus therapies enables universal treatment access, lowers costs and incentivizes innovation and competition.

BACKGROUND AND AIMS: High unit prices of treatments limit access. For epidemics like that of hepatitis C virus (HCV), reduced treatment access increases prevalence and incidence, making the infectious disease increasingly difficult to manage. The objective of the current study was to construct and test an alternative pricing model, the Payer License Agreement (PLA), and determine whether it could improve outcomes, cut costs and incentivize innovation versus the current unit-based pricing model. METHODS: We built and used computational models of hepatitis C disease progression, treatment, and pricing in historical and future scenarios and quantitatively analyzed their economic and epidemiological impact in three high-income countries. RESULTS: This study had three key results regarding HCV treatment. First, if the PLA model had been implemented when interferon-free direct-acting antiviral (DAA) combinations launched, the number of patients treated and cured would have more than doubled in the first three years, while the liver-related deaths (LRDs) would have decreased by around 40%. Second, if the PLA model had been implemented beginning in 2018, the year that several Netflix-like payment models were under implementation, the number of treated and cured patients would nearly double, and the LRDs would decline by more than 55%. Third, implementing the PLA model would result in a decline in total payer costs of more than 25%, with an increase to pharmaceutical manufacturer revenues of 10%. These results were true across the three healthcare landscapes studied, the USA, the UK and Italy, and were robust against variations to critical model parameters through sensitivity analysis. CONCLUSIONS AND RELEVANCE: These results suggest that implementation of the PLA model in high-income countries across a variety of health system contexts would improve patient outcomes at lower payer cost with more stable revenue for pharmaceutical manufacturers. Health policy-makers in high-income countries should consider the PLA model for application to more cost-effective management of HCV, and explore its application for other infectious diseases with curative therapies available now or soon.

HCV disease burden and population segments in Switzerland.

BACKGROUND: Switzerland has made strides towards hepatitis C virus elimination, but as of 2019, elimination was not guaranteed. However, political interest in viral hepatitis has been increasing. We sought to develop a better understanding of Switzerland's progress towards HCV elimination and the profile of remaining HCV-RNA-positive patients. METHODS: A previously described Markov model was updated with recent diagnosis and treatment data and run to generate new forecasts for HCV disease burden. Two scenarios were developed to evaluate HCV morbidity and mortality under the status quo and a scenario that achieves the Swiss Hepatitis Strategy Elimination targets. Next, an analysis was conducted to identify population segments bearing a high burden of disease, where future elimination efforts could be directed. RESULTS: At the beginning of 2020, an estimated 32 100 viremic infections remained in Switzerland (0.37% viremic prevalence). Adult (≥18 years of age) permanent residents born abroad represented the largest subpopulation, accounting for 56% of HCV infections. Thirteen countries accounted for ≥60% of viremic infections amongst permanent residents born abroad, with most people currently residing in Zurich, Vaud, Geneva, Bern, Aargau and Ticino. Amongst Swiss-born HCV-RNA-positive persons, two-thirds had a history of IDU, corresponding to 33% of total infections. CONCLUSIONS: In Switzerland, extra efforts for diagnosis and linkage to care are warranted in foreign-born populations and people with a history of drug use. Population-level measures (eg increasing the number of providers, increase screening) can identify patients who may have otherwise fallen through the gaps or avoided care because of stigma.

Global prevalence of hepatitis C virus in women of childbearing age in 2019: a modelling study.

BACKGROUND: Treatment for infection with hepatitis C virus (HCV) during pregnancy has not yet been approved; however, interventions specifically targeting women, especially those of childbearing age (15-49 years), could prevent vertical transmission and community spread. To assess the impact of such interventions, improved prevalence estimates in this group are needed. We aimed to estimate the global prevalence of viraemic HCV in 2019 among women of childbearing age. METHODS: In this modelling study, we used previously developed models for 110 countries inputted with country-specific demographic and HCV epidemiology data. We did a literature review, searching PubMed, Embase, and grey literature for studies published between Jan 1, 2000, and June 30, 2018, reporting HCV antibody or viraemic prevalence in women of childbearing age. Studies from the literature review and studies in models were compared by use of a data quality scoring system and models were updated, as appropriate, when a better study was identified. We used these HCV disease burden models to calculate the 2019 prevalence of viraemic HCV in women of childbearing age. In countries without a model, prevalence was extrapolated by Global Burden of Disease (GBD) region. FINDINGS: An estimated 14 860 000 (95% uncertainty interval [UI] 9 667 000-18 282 000) women aged 15-49 years had HCV infection worldwide in 2019, corresponding to a viraemic prevalence of 0·78% (95% UI 0·62-0·86). Globally, HCV prevalence increased with age, rising from 0·25% (95% UI 0·20-0·27) in women aged 15-19 years to 1·21% (0·97-1·34) in women aged 45-49 years. China (16% of total infections) and Pakistan (15%) had the greatest numbers of viraemic infections, but viraemic prevalence was highest in Mongolia (5·14%, 95% CI 3·46-6·28) and Burundi (4·91%, 3·80-18·75). Of the countries with 500 cases or more, viraemic prevalence was lowest in Chile (0·07%, 95% UI 0·04-0·12). Among the GBD regions, eastern Europe had the highest viraemic prevalence (3·39%, 95% UI 1·88-3·54). By WHO region, the Eastern Mediterranean region had the highest viraemic prevalence (1·75%, 95% UI 1·26- 1·90). INTERPRETATION: Most research on HCV disease burden among women aged 15-49 years focuses on pregnant women. Using modelling, this analysis provides global and national estimates of HCV prevalence in all women of childbearing age. These data can inform preconception test-and-treat strategies to reduce vertical transmission and total disease burden. FUNDING: Gilead Sciences, John C Martin Foundation, private donors.

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.

The Hep-CORE policy score: A European hepatitis C national policy implementation ranking based on patient organization data.

BACKGROUND: New hepatitis C virus (HCV) treatments spurred the World Health Organization (WHO) in 2016 to adopt a strategy to eliminate HCV as a public health threat by 2030. To achieve this, key policies must be implemented. In the absence of monitoring mechanisms, this study aims to assess the extent of policy implementation from the perspective of liver patient groups. METHODS: Thirty liver patient organisations, each representing a country, were surveyed in October 2018 to assess implementation of HCV policies in practice. Respondents received two sets of questions based on: 1) WHO recommendations; and 2) validated data sources verifying an existing policy in their country. Academic experts selected key variables from each set for inclusion into policy scores. The similarity scores were calculated for each set with a multiple joint correspondence analysis. Proxy reference countries were included as the baseline to contextualize results. We extracted scores for each country and standardized them from 0 to 10 (best). RESULTS: Twenty-five countries responded. For the score based on WHO recommendations, Bulgaria had the lowest score whereas five countries (Cyprus, Netherlands, Portugal, Slovenia, and Sweden) had the highest scores. For the verified policy score, a two-dimensional solution was identified; first dimension scores pertained to whether verified policies were in place and second dimension scores pertained to the proportion of verified policies in-place that were implemented. Spain, UK, and Sweden had high scores for both dimensions. CONCLUSIONS: Patient groups reported that the European region is not on track to meet WHO 2030 HCV goals. More action should be taken to implement and monitor HCV policies.

Do the most heavily burdened countries have the right policies to eliminate viral hepatitis B and C?

In 2019, a Lancet Gastroenterology & Hepatology Commission on accelerating the elimination of viral hepatitis reported on the status of 11 viral hepatitis policy indicators in 66 countries and territories with the heaviest burden by global region. Policies were reported as being either in place, in development, or not in place. This study uses the Commission findings to estimate hepatitis B virus (HBV) and hepatitis C virus (HCV) policy scores and rankings for these 66 countries and territories. We applied a multiple correspondence analysis technique to reduce data on policy indicators into a weighted summary for the HBV and HCV policies. We calculated HBV and HCV policy scores for each country. Countries and territories that received higher scores had more policies in place and in development than did countries with lower scores. The highest scoring country for HBV was Australia, whereas Somalia had the lowest score. For the HCV policy score, Australia and New Zealand had perfect scores, whereas Somalia, Sudan, and Yemen had the lowest scores, all having no policy indicators in place.

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.

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.

Nonalcoholic fatty liver disease burden: Australia, 2019-2030.

BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) account for a large and growing proportion of liver disease burden globally. The burden of NAFLD/NASH manifests in increasing levels of advanced liver disease and primary liver cancer in Australia. A Markov model was used to forecast NAFLD burden in Australia through 2030. METHODS: A model was used to estimate fibrosis progression, primary liver cancer, and liver deaths among the Australian NAFLD population, with changes in incident NAFLD cases based on long-term trends for changes in the prevalence of obesity. Published estimates and surveillance data were applied to build and validate the model projections, including surveillance data for the incidence of liver cancer. RESULTS: Prevalent NAFLD cases were projected to increase 25% from the current burden (5 551 000 [4 748 000-6 306 000] cases in 2019) to 7 024 000 [5 838 000-7 886 000] cases in 2030. The projected increase in the number of NASH cases (40%) was greater than that of NAFLD cases. Incident cases of advanced liver disease are projected to increase up to 85% by 2030, and incident NAFLD liver deaths are estimated to increase 85% from 1900 (1100-3300) deaths in 2019 to 3500 (2100-6100) deaths in 2030. CONCLUSIONS: Restraining growth of the obese and diabetic populations, along with potential therapeutic options, will be essential for mitigating disease burden.