Dr Zisis Kozlakidis and Dr Dewi Nur Aisyah examine Hepatitis C virus elimination and weigh up if this has the potential to become a global success story
Hepatitis C virus (HCV) infection is recognised as the worldwide leading cause of chronic liver disease and a leading cause of liver cancer. The virus can cause acute and chronic hepatitis, ranging in severity from a very mild illness to a serious, lifelong illness, including liver cirrhosis and cancer. In particular, acute HCV infections are usually asymptomatic, and most do not lead to a life-threatening disease, while an estimated average of 30% of infected persons spontaneously clear the virus within 6 months of infection without any treatment. However, the remaining 70% of infected persons will develop chronic HCV infection, highlighting our need for Hepatitis C virus elimination.
Of those with chronic HCV infection, the risk of chronic liver disease ranges from 15% to 30% within 20 years. The World Health Organization (WHO) estimated the worldwide HCV infection prevalence at approximately 1%, representing about 71 million people who are chronically infected and causing 1.34 million deaths in 2015 (1), reduced to a still considerable 0.4 million deaths by 2019. It becomes evident from the above that HCV infections will be presenting with a range of different symptoms across the population and at different time points, thus demanding a complex pathway of preventing, treating and eventually eliminating this disease.
HCV transmission through different routes
The hepatitis C virus is a bloodborne virus that infects people across all continents, with most infections occurring through exposure to blood from unsafe injection practices, unsafe health care, unscreened blood transfusions, injection drug use and sexual practices that lead to exposure to blood. For example, in the United Kingdom (UK), around 200,000 people are chronically infected by HCV, the majority of whom are from marginalised and under-served groups in society, such as people who inject drugs (2). London has the highest laboratory reports of HCV infection among other cities in England, with around 60,000 HCV cases reported in 2015, although this number is showing a steady, albeit slow, decrease in the last years and following the expansion of access to direct-acting antiviral (DAA) treatments. In other countries, the profile of HCV infections is very different. For example, in Egypt, HCV infection is a major public health burden, as the country bears the highest prevalence rate in the world. In the latter case, most HCV infections relate to unsafe clinical practices. Over two decades of national schistosomiasis treatment (mainly during the ‘60s and ‘70s), 36 million injections were administered to >6 million people, almost all with unsterilized and shared syringes and needles, facilitating the spread of HCV across the population. This represents the largest ever iatrogenic spread of blood-borne infection (3). However, even in the case of Egypt, with a heavy population infection burden, there is significant, steady progress made in the prevention and control of further HCV spread.
HCV elimination roadmaps
This gradual reduction in HCV infections and deaths in the last decade has invigorated the discussions relating to a potential HCV elimination. Such an elimination could have a tremendous impact on global health, averting the nearly 0.4 million deaths from HCV-related complications each year. In line with this vision, the WHO set an ambitious goal of eliminating viral hepatitis by 2030 (defined as a 90% reduction in new chronic infections and a 65% reduction in mortality, compared with the 2015 baseline). Specifically, in May 2016, the World Health Assembly adopted the first Global health sector strategy on viral hepatitis (2016–2020), highlighting the critical role of universal health coverage and implementing key prevention, diagnosis, treatment, and community intervention strategies for Hepatitis C virus elimination.
More recently, in May 2022, the 75th World Health Assembly noted a new set of integrated global health sector strategies on HIV, viral hepatitis and sexually transmitted infections for the period of 2022–2030. These roadmaps currently provide the backbone for national comprehensive Hepatitis C virus elimination strategies and programmes.
Immunology complementing public health initiatives
Even though the ability to define public health strategies constitutes a large part of the picture, many aspects still remain to be understood relating to the molecular biology and immunology of the virus. For example, understanding the ability of the virus to mutate and evade the human immune responses is critical in maintaining an effective clinical armament towards controlling the virus. Specifically, it is still not fully understood how HCV evades antibody and T-cell responses to establish persistent infection. Recent studies have demonstrated the plasticity of the HCV genetic information to allow rapid responses to changing selection pressures by antibodies (4). An additional complication is the overall genetic diversity of HCV, as to date, there are at least seven genotypes, and 67 subtypes of HCV found worldwide that differ by up to 30% in their overall genetic information. In the recent past, determining the HCV genotype became an important clinical parameter in selecting PEGylated interferon antiviral therapy, which could influence the treatment effectiveness rate. In the current era of effective DAAs, it is likely that understanding this genetic variation will be critical in the design of effective vaccines in the future, as any vaccines would need to be addressing the wide genetic variation of the circulating virus.
Hepatitis C virus elimination can become a reality
A major global burden imposed by HCV is gradually being controlled by a combination of improved diagnoses, a more coherent global public health response, and well-informed healthcare systems providing novel treatments, such as the DAA treatments, to increasingly larger population groups. Therefore, Hepatitis C virus elimination can become a reality in the near future and another tangible clinical success story. However, challenges remain along the way, such as the further understanding of the immunology of the virus as well as the HCV vaccine development, which is a unique challenge from many perspectives, including being able to address the wide genetic variation of circulating viral strains. Thus, it is foreseeable that in order to effectively control this complex disease, an equally as multifaceted set of coordinated activities would need to be maintained for the next decade.
References
- WHO, Global Hepatitis Report 2017, Geneva, Switzerland. https://www.who.int/publications/i/item/9789241565455
- Aisyah DN, Shallcross L, Hayward A, et al.: Hepatitis C among vulnerable populations: A seroprevalence study of homeless, people who inject drugs and prisoners in London. J Viral Hepat. 2018; 25(11): 1260–1269.
- Frank C, Mohamed MK, Strickland GT, et al. The role of parenteral antischistosomal therapy in the spread of hepatitis C virus in Egypt. Lancet. 2000;355(9207):887–891.
- Stejskal, Lenka, et al. “An entropic safety catch controls hepatitis C virus entry and antibody resistance.” Elife 11 (2022): e71854.
Where authors are identified as personnel of the International Agency for Research on Cancer/WHO, the authors alone are responsible for the views expressed in this article, and they do not necessarily represent the decisions, policies or views of the International Agency for Research on Cancer/WHO.
