Scaling up prevention and treatment towards the elimination of hepatitis C: a global mathematical model

Abstract

Background: The revolution in hepatitis C virus (HCV) treatment through the development of direct-acting antivirals (DAAs) has generated international interest in the global elimination of the disease as a public health threat. In 2017, this led WHO to establish elimination targets for 2030. We evaluated the impact of public health interventions on the global HCV epidemic and investigated whether WHO's elimination targets could be met.

Methods: We developed a dynamic transmission model of the global HCV epidemic, calibrated to 190 countries, which incorporates data on demography, people who inject drugs (PWID), current coverage of treatment and prevention programmes, natural history of the disease, HCV prevalence, and HCV-attributable mortality. We estimated the worldwide impact of scaling up interventions that reduce risk of transmission, improve access to treatment, and increase screening for HCV infection by considering six scenarios: no change made to existing levels of diagnosis or treatment; sequentially adding the following interventions: blood safety and infection control, PWID harm reduction, offering of DAAs at diagnosis, and outreach screening to increase the number diagnosed; and a scenario in which DAAs are not introduced (ie, treatment is only with pegylated interferon and oral ribavirin) to investigate the effect of DAA use. We explored the effect of varying the coverage or impact of these interventions in sensitivity analyses and also assessed the impact on the global epidemic of removing certain key countries from the package of interventions.

Findings: By 2030, interventions that reduce risk of transmission in the non-PWID population by 80% and increase coverage of harm reduction services to 40% of PWID could avert 14·1 million (95% credible interval 13·0-15·2) new infections. Offering DAAs at time of diagnosis in all countries could prevent 640 000 deaths (620 000-670 000) from cirrhosis and liver cancer. A comprehensive package of prevention, screening, and treatment interventions could avert 15·1 million (13·8-16·1) new infections and 1·5 million (1·4-1·6) cirrhosis and liver cancer deaths, corresponding to an 81% (78-82) reduction in incidence and a 61% (60-62) reduction in mortality compared with 2015 baseline. This reaches the WHO HCV incidence reduction target of 80% but is just short of the mortality reduction target of 65%, which could be reached by 2032. Reducing global burden depends upon success of prevention interventions, implemention of outreach screening, and progress made in key high-burden countries including China, India, and Pakistan.

Interpretation: Further improvements in blood safety and infection control, expansion or creation of PWID harm reduction services, and extensive screening for HCV with concomitant treatment for all are necessary to reduce the burden of HCV. These findings should inform the ongoing global action to eliminate the HCV epidemic.

Funding: Wellcome Trust.

Figure 1

Model structure Boxes represent compartments of the model and arrows denote annual transition rates that can depend upon age, sex, risk group, or duration of infection that can vary over time. At any given point, every person is in one compartment of the cascade of care (A). These compartments are further subdivided by age, sex, and risk group. Spontaneous clearance occurs in a fraction of those acutely infected who return to the susceptible population. Treatment can result in cure and reinfection can occur after successful treatment. Infection results in people entering the natural history model (B): HCV disease progresses through five METAVIR fibrosis stages, from F0 (no fibrosis) to F4 (compensated cirrhosis). The potential effects of age and male sex on progression and mortality rates are accounted for in calibration. People in the cured compartment of the treatment cascade have reduced or zero disease progression rates depending on disease stage. See appendix for full details, including a list of parameter values with dependencies and the complete model structure diagram. HCV=hepatitis C virus.

Figure 2

Calibration results (A) Comparison of the model's simulated prevalence of HCV with prevalence data for all 190 countries simulated,, , , colour-coded by GBD super-region (see appendix for the full list of regions). Overall prevalence values are from 2015 whereas PWID values come from a range of years. The diagonal lines mark equivalent estimates. (B) Comparison of modelled HCV mortality numbers with IHME HCV mortality estimates., Countries were calibrated to age-stratified and sex-stratified mortality estimates; modelled outputs were summed into overall cirrhosis and hepatocellular carcinoma mortality numbers and compared with aggregated IHME estimates for the years 1990, 1995, 2000, 2005, 2010, and 2015. GBD=Global Burden of Disease Study. HCV=hepatitis C virus. IHME=Institute for Health Metrics and Evaluation. PWID=people who inject drugs.

Figure 3

Global intervention results (A) Number of deaths due to HCV by scenario. Note that due to the high impact of the comprehensive package of interventions (intervention 4) on reducing the number of deaths, the credible intervals are extremely narrow around the median. (B) Incidence of viraemic HCV infection (number of incident chronic infections divided by number of people susceptible) by scenario. Note that the incidence curves for interventions 2 and 3 are almost coincident. Vertical dashed lines indicate baseline (2015) and the year for targeted elimination (2030). Horizontal dashed lines indicate elimination targets: 65% reduction of mortality and 80% reduction in incidence. In panels (C) and (D), data are shown by GBD region. The end of each bar represents the median year of mortality (C) or incidence (D) elimination. Grey bars show the status quo scenario; the red portion of each bar shows the comprehensive package of interventions (intervention 4). Where a red bar extends to the edge of the graph, elimination was not achieved in any scenario before 2100. The dashed vertical line indicates the WHO elimination year target of 2030. DAA=direct-acting antivirals. GBD=Global Burden of Disease Study. HCV=hepatitis C virus. PWID=people who inject drugs.

Figure 4

Distribution of global deaths averted and infections averted when implementing the comprehensive package of interventions compared with the status quo scenario Cumulative deaths and infections averted in 2017–30 are shown by country as percentages of the total global number averted.

Figure 5

Reduction in mortality and incidence in the status quo scenario upon improving prevention or screening intervention coverage Changes in mortality and incidence by 2030 upon increasing the reduction in general population (ie, non-PWID) risk, the coverage of PWID harm reduction interventions, and the proportion diagnosed by 2030, from status quo values. The vertical dashed lines show the values targeted in the intervention scenarios (see table).