Modelling the Potential Prevention Benefits of a Treat-all Hepatitis C Treatment Strategy at Global, Regional and Country Levels

A Modelling Study

Adam Trickey; Hannah Fraser; Aaron G. Lim; Josephine G. Walker; Amy Peacock; Samantha Colledge; Janni Leung; Jason Grebely; Sarah Larney; Natasha K. Martin; Louisa Degenhardt; Matthew Hickman; Margaret T. May; Peter Vickerman


J Viral Hepat. 2019;26(12):1388-1403. 

In This Article

Abstract and Introduction


The World Health Organization (WHO) recently produced guidelines advising a treat-all policy for HCV to encourage widespread treatment scale-up for achieving HCV elimination. We modelled the prevention impact achieved (HCV infections averted [IA]) from initiating this policy compared with treating different subgroups at country, regional and global levels. We assessed what country-level factors affect impact. A dynamic, deterministic HCV transmission model was calibrated to data from global systematic reviews and UN data sets to simulate country-level HCV epidemics with ongoing levels of treatment. For each country, the model projected the prevention impact (in HCV IA per treatment undertaken) of initiating four treatment strategies; either selected randomly (treat-all) or targeted among people who inject drugs (PWID), people aged ≥35, or those with cirrhosis. The IA was assessed over 20 years. Linear regression was used to identify associations between IA per treatment and demographic factors. Eighty-eight countries (85% of the global population) were modelled. Globally, the model estimated 0.35 (95% credibility interval [95%CrI]: 0.16–0.61) IA over 20 years for every randomly allocated treatment, 0.30 (95%CrI: 0.12–0.53) from treating those aged ≥35 and 0.28 (95%CrI: 0.12–0.49) for those with cirrhosis. Globally, treating PWID achieved 1.27 (95%CrI: 0.68–2.04) IA per treatment. The IA per randomly allocated treatment was positively associated with a country's population growth rate and negatively associated with higher HCV prevalence among PWID. In conclusion, appreciable prevention benefits could be achieved from WHO's treat-all strategy, although greater benefits per treatment can be achieved through targeting PWID. Higher impact will be achieved in countries with high population growth.


Hepatitis C virus (HCV) is a bloodborne infection.[1] Globally, over 70 million people are infected with HCV.[2] An estimated 400 000 people die annually due to HCV-related disease.[1,3,4]

Direct-acting antiviral (DAA) treatments have made HCV an easily curable infection.[5] In 2016, the World Health Organization (WHO) published a Global Health Sector Strategy for eliminating HCV as a public health threat by 2030,[6] setting targets to reduce the incidence of new infections by 80%, and HCV-related mortality by 65%. Meeting these targets requires governments to efficiently allocate resources for treating HCV infections, especially where DAA prices are high or resources are low.[7]

Historically, the emphasis has been on treating people with advanced liver disease.[8] However, a wider allocation of treatment is required to eliminate HCV. To encourage widespread treatment scale-up, WHO produced guidelines in 2018 advising that countries should allow access to HCV treatment for all infected individuals: a 'treat-all' strategy.[9] This HCV treatment strategy will produce clinical benefits, such as reducing the risks of severe liver disease,[10] and should also prevent new infections from occurring through treating individuals with ongoing transmission risk.[11] Previous analyses have considered who should be treated to achieve greatest morbidity and mortality benefits,[12–14] whilst other analyses have considered the cost-effectiveness of different treatment strategies.[13] However, these analyses have generally not included prevention benefits unless they focussed on people who inject drugs (PWID), assuming these benefits would be negligible when not treating such high-risk groups.[15] To help countries understand the overall benefits of WHO's new treat-all policy, it is important to evaluate its prevention benefits and determine how country-level demographic and epidemiological differences could affect the prevention benefits achieved.

Indeed, HCV epidemics vary widely between countries, with most of the HCV burden in high-income countries being due to needle and syringe sharing among people who inject drugs (PWID),[16,17] whilst medical and community risk factors are important in most low- and middle-income countries (LMICs).[18,19] These epidemic differences will affect the prevention benefits achieved from a treat-all strategy.

We use dynamic HCV transmission modelling to determine the HCV infections averted (IA) per DAA treatment at a global, regional and country level for a random treat-all strategy, comparing it with treating other subgroups and evaluating how the impact achieved depends on different country-specific factors. Whilst other studies have investigated the morbidity and mortality benefits from different treatment allocations,[13,14] this study focuses on modelling the prevention of subsequent chronic HCV infections, comparing a treat-all policy to treating just PWID, individuals with cirrhosis or those aged ≥35 years.