The key finding of this study is that only one in five of the examined high-income countries is on track to achieve the HCV elimination targets by 2030, and two out of every three are off-track by at least 20 years. These results are largely unchanged even upon considering the low country-specific chronic HCV prevalence in the sensitivity analysis. Part of this delay may be due to the fact that in 2017, over half of all high-income countries analyzed still had restrictions in place that limited access to highly effective pan-genotypic DAAs. Since this analysis was conducted, Belgium, Denmark, Finland, Greece, Israel, New Zealand, Norway, Slovenia, Sweden and Taiwan have removed their restrictions. However, even upon excluding restrictions on treatment by fibrosis score as a criterion for elimination, none of the countries considered would be on track to eliminate HCV by 2030. Simulating the Greek model with restrictions on treatment by fibrosis score lifted would achieve the incidence target by 2050, but it would still be off track to achieve the treatment target due to the low level of antiviral treatments. Similarly, the United States' fragmented healthcare system continues to have restrictions in place for patients to access the new therapies. The elimination of hepatitis C may not be possible without full access to antiviral therapies in key populations, including persons who inject drugs, are incarcerated, or have mild liver fibrosis.
Mortality and treatment targets are closely linked as increased treatment rates will reduce disease progression and mortality. As such, treatment rate remains low in most high-income countries and most are below the required number needed to treat, as 26 (58%) of the 45 countries are not expected to meet the treatment target by 2030, while 15 (33%) are not expected to meet the treatment target by 2050. Of these 15 countries, only two (Greece and Taiwan) are projected to meet the mortality target by 2050. Notably, both Greece and Taiwan had restrictions on treatment by fibrosis score in 2017, therefore unrestricted treatment is not a pre-requisite to meeting the mortality target. Similarly, many countries lack screening programs to diagnose those infected with HCV and link them to care. Of the 45 high-income countries analyzed, 21 (47%) will not reach the target of diagnosing at least 90% of the infected population before 2030. In the majority (60%) of the 45 high-income countries considered, less than half of the HCV-infected population had been diagnosed by 2017, and linking the patients who are unaware of their status to care using screening programs is a critical step in achieving elimination.
These findings suggest the need for a framework to provide countries guidance on the key success factors for eliminating HCV as a public health threat by 2030. Based on the experience of the nine high-income countries expected to meet the WHO targets by 2030, we propose eight key success factors for HCV elimination (Table 2): (a) political will to achieve the WHO elimination targets, (b) a national program that is financed, (c) implementation of or in-place harm reduction programs, (d) expanded treatment capacity beyond specialists, (e) removal of treatment restrictions, (f) monitoring and evaluation of existing programs, (g) implementation of awareness and screening programs, and (h) implementation of linkage-to-care programs (Figure 3). As Table 2 shows, not all factors may be required for achieving HCV elimination by 2030. For example, Iceland had already diagnosed the majority of its HCV-infected population and did not require a large screening program. Furthermore, the small number of HCV patients in that country can be treated by liver specialists only, so there is no need to expand treatment capacity. On the other hand, Switzerland lacks a formal national hepatitis elimination plan but is expected to achieve elimination by 2025. Germany has a general strategy for HCV without any specific targets, while Austria has none, yet they are off track towards elimination by only 1 and 2 years, respectively. Similarly, Malta only launched its national HCV strategy in 2018 but is only off track by 4 years. While no single factor is sufficient for achieving HCV elimination by 2030, three stand out as necessary: political will, removal of treatment restrictions, and monitoring and evaluation of existing programs were all in place for every country on track towards HCV elimination by 2030.
There were several limitations to this study. The calculation of liver-related deaths only considered the currently HCV-infected population. Studies have shown that following a sustained virologic response, some cirrhotic patients may continue to progress to decompensated cirrhosis, hepatocellular carcinoma, or liver-related death; however, the rate of progression is substantially reduced. The analysis also assumed a constant number of diagnosed and treated patients annually from 2017 forward. However, in most countries the number of patients treated is actually decreasing from peak levels, suggesting our estimated timing of HCV elimination may be optimistic. Based on the best available data in high-income countries, the study used the restrictions on antiviral treatment by fibrosis score from 2017 as the status quo. As shown above, several countries have since lifted these restrictions, which would lead to a better prognosis for these countries. This study only considered the impact of antiviral treatment on the incidence of HCV infection. The reduction in incidence resulting from harm reduction programs was not modelled as the presence and scope of these programs varied widely across countries. While the impact of expanding treatment to all fibrosis scores and high-risk populations on the incidence of HCV infection has been previously shown, the additional benefit of needle and syringe programs and opiate substitution therapy has also been documented. Therefore, our projections of reduction in incidence are conservative, and employing harm reduction programs would lead to more optimistic future outcomes, and hence accelerate the path towards HCV elimination. Also, the transmission of HCV occurring among persons who inject drugs or other risk groups was not explicitly modelled and HCV incidence may not necessarily be a linear function of chronic prevalence depending on the relative size of these groups to the general population. Furthermore, our analysis only considered high-income countries on the premise that they have appropriate healthcare systems for pursuing a path towards the elimination of HCV. Based on this premise, we would expect even more limited progress towards HCV elimination in middle- and low-income countries. Lastly, the proposed conceptual framework for HCV elimination may require further assessment, measurement and validation.
In conclusion, despite the desire to eliminate hepatitis C by 2030, only a few high-income countries will be able to achieve the targets outlined by the WHO. Treatment restrictions need to be removed, harm reduction programs need to be increased, screening programs need to be implemented, and treatment rates need to increase to achieve these targets. In addition, the national programs need to provide financing, expand treatment capacity beyond specialists when sufficient numbers are not available, implement monitoring and evaluation programs to track progress, linkage-to-care programs need to be instituted to make sure diagnosed patients can be treated, and awareness campaigns are needed to increase the visibility of these programs. Without political will, it is unlikely that HCV elimination targets will be met, as programs may lack sustained commitment and funding. We call for action from all stakeholders involved to help achieve the strategy recommended by the 69th World Health Assembly.
Medical writing support was provided by Ivane Gamkrelidze, employee of Center for Disease Analysis, who contributed to the data analysis and/or the drafting of the article. AbbVie Inc provided funding for this medical writing support.
DAA, direct-acting antiviral; HCV, hepatitis C virus; METAVIR, meta-analysis of histological data in viral hepatitis; SVR, sustained virologic response; WHO, World Health Organization.
The design, analysis and financial support of this study were provided by AbbVie Inc AbbVie Inc participated in the interpretation of data, review and approval of the study.
Liver International. 2020;40(3):522-529. © 2020 Blackwell Publishing