Methods
A previously published Markov disease progression model of HCV infection[4] was populated with demographic (population, all-cause mortality rate, fertility rate, sex ratio at birth) and epidemiological (genotype distribution of HCV, number of new diagnoses, antiviral treatments, liver transplantations due to HCV infection) inputs for 45 high-income countries per the World Bank's 2019 income group classification[5] using a previously described search strategy.[4] With the exception of Cyprus, Kuwait and Singapore, the historical chronic prevalence of HCV infection forecasted by the model had been previously published for all countries.[4] The countries considered in the analysis are listed in Table 1, comprising high-income countries with appropriate healthcare systems for pursuing a path towards the elimination of HCV. The model forecasted the annual HCV-infected population and liver-related deaths due to HCV infection by stage of liver disease, sex and age. The diagram of the Markov model is shown in Figure 1. Since the original publication, the calculation of incidence in the model has been updated: first, the incident HCV infections were separated into vertically and horizontally acquired infections; second, the horizontally acquired infections were calculated as a function of chronic prevalence in the future years.
Figure 1.
Markov model of HCV infection. HCV, hepatitis C virus
Vertically acquired infections were calculated by applying the mother-to-child transmission rate of HCV[6] to the modelled age group-specific chronic prevalence of HCV and reported fertility rates among women of childbearing age.[7] HCV-infected infants entered the disease burden model at age zero by sex, and their subsequent disease progression was tracked.
Horizontally acquired infections were calculated separately for historical and future years. Historical incident cases were calibrated to reported overall, as well as sex- and age group-specific, prevalence of chronic HCV infection in a country using a previously described calibration procedure.[4] Selection criteria for reported HCV prevalence data are described in the Appendix S1. Future incident cases were assumed to change at the same annual rate as chronic prevalent cases (F0 or overall) of HCV infection, relative to 2017. In countries with treatment or reimbursement restrictions on the basis of fibrosis stage (eg F1 or greater on the METAVIR scale), the rate of change in incident cases was tied to the rate of change in modelled F0 prevalence. In countries without treatment or reimbursement restrictions by fibrosis stage, the rate of change in incident cases was based on the rate of change in all chronic prevalent cases. Maintaining the standard of care in 2017 (number of new diagnoses and antiviral treatments, treatment eligibility and average sustained virologic response) was defined as the status quo. 2017 was chosen since this was the last year of complete treatment data and the latest year of prevalence data available for all countries analyzed.
Modelled outcomes for chronic prevalence, incidence, liver-related deaths due to HCV infection, as well as reported data on diagnosis and antiviral treatment of HCV infection were analyzed to determine the year in which a country would meet the four WHO targets to eliminate HCV as a public health threat by 2030:[2] an 80% reduction in incidence of chronic HCV infections between 2015 and 2030, 65% reduction in liver-related deaths due to chronic HCV infection between 2015 and 2030, 90% diagnosis coverage of the HCV-infected population in 2015 and 80% treatment coverage of eligible HCV-infected population in 2015. In line with the diagnosis coverage target, 90% of the chronic prevalent population was considered treatment-eligible. The earliest year in which all four targets were met was defined as the year of HCV elimination. If this year was before 2030 (inclusive), a country was considered on track towards elimination by 2030; if the year was before 2040 or 2050 (inclusive), off-track but expected to achieve elimination by 2040 or 2050, respectively; if the year was after 2051 (inclusive), off-track and not expected to achieve elimination by 2050. Countries with restrictions on treatment by fibrosis score were considered off-track to eliminate HCV before 2050, regardless of modelled outcomes.
Lastly, the average number of annual antiviral treatments (starting in 2020) necessary to achieve the WHO's treatment coverage target was calculated for countries that were not on track to achieve the target by 2030. For this calculation, 80% of the treatment-eligible population, as defined above, less cumulative treatments over 2015–2019, was divided by 11 (the number of years between 2020 and 2030).
A sensitivity analysis for each country was conducted by simulating the models at the previously reported low and high reported country-specific chronic HCV prevalence,[4] which provided the best- and the worst-case scenarios for the years of elimination and the number of treatments necessary to achieve the treatment coverage target.
Liver International. 2020;40(3):522-529. © 2020 Blackwell Publishing
