by Kristen Ashworth

Graphic design by Genevieve Groulx

Hepatitis C Virus (HCV), alongside the commonly associated hepatitis B, is recognized as a significant global health concern. In fact, by 2040, chronic infection by these two blood-borne diseases will cause more deaths than HIV, tuberculosis, and malaria combined.¹ HCV raises particular concern due to its propensity to progress into a chronic condition. It is often referred to as a ‘silent killer’ because it can manifest without symptoms and quietly develop in a host for decades before eventual diagnosis, which often coincides with the emergence of advanced-stage liver disease or liver cancer.

Fortunately, there has been remarkable progress in treatment for HCV. With well-tolerated oral therapy, HCV can be cured in almost all those treated, making it the first curable chronic viral infection. This has led the World Health Organization (WHO) to an ambitious goal: to eliminate viral hepatitis as a public health threat by 2030. However, there is currently no vaccine to help prevent transmission of HCV from occurring in the first place. Without this, true eradication of HCV is near impossible.

Determined to overcome this challenge is Dr. Jordan Feld, a trailblazer in the field of hepatitis research. Dr. Feld is a clinician-scientist at Toronto General Hospital, where he works as a hepatologist and is the interim Director of the Toronto Centre for Liver Disease. Together with his lab and an esteemed team of collaborators from across Canada, his mission is to eliminate HCV in our country within the next decade. 

To reach this target, Dr. Feld’s team is using a two-armed approach. The first is to investigate strategies to improve both HCV diagnosis and the dissemination of antiviral drug treatment for those already infected with the virus. This is a collaborative effort that is being facilitated in conjunction with CanHepC, the Canadian Network on Hepatitis C, which seeks to tackle the current landscape of health outcomes for people living with HCV at all stages of care. The network has worked together to establish a national framework, entitled the Blueprint, that sets measurable goals in accordance with HCV elimination efforts that aim to bridge the gap between epidemiology, public policy, and scientific discovery in HCV research. Dr. Feld explains why the Blueprint, which focuses on diagnosis and care, is an important piece of the puzzle to eradicate HCV, but acknowledges that there are inherent challenges in disseminating this care to Canadians who need it. “All the people who are undiagnosed living with hepatitis C – how do we find them and get them into care?” he asks. “How do we overcome some of the social, financial and other barriers that inhibit people from accessing this care?” To address these obstacles, Dr. Feld has co-led the development of the Roadmap for HCV Elimination in Ontario that was launched earlier this year and brings together stakeholders across the province to address specific barriers to HCV prevention, care, and treatment to ensure we reach the elimination targets within the province. 

The second arm of Dr. Feld’s research involves developing the HCV vaccine itself. To guide their current vaccine work, Dr. Feld’s team first evaluated HCV transmission events by studying the virus in people who received organ transplants from donors with HCV. Prior to this work, donors with HCV were not considered for organ donation due to the risk of HCV transmission to the recipient. Dr. Feld’s team found that HCV infection from a donor can be efficiently treated post-transplant and, remarkably, can even be prevented by starting therapy before the transplant. This approach to organ transplantation has now been adopted as an effective standard of care at Toronto General Hospital and is being implemented at other centres across Canada, increasing organ availability and providing life-saving opportunities for patients who otherwise may die on a transplant waitlist. 

This research also shed new light on the variable nature of HCV itself. In a single infected person, billions of related but slightly distinct variants of HCV circulate, making it among the most variable human pathogens known, and serving as a major impediment to vaccine development.² Dr. Feld’s team is carefully studying the specific variants of the virus that are transmitted to organ recipients, which they hope will allow them to identify what needs to be targeted by a vaccine. Dr. Feld explains, “We know from all these variants that exist in a donor [that] only a very small number of them actually establish infection.” From this understanding, the path toward discovery of a broad-spectrum HCV vaccine became clearer. To this end, Dr. Feld’s team used a novel strategy that combined different versions of an extremely variable region of the virus to train the immune system to find commonalities amongst the diversity. Antibodies generated in mice that received this vaccine candidate prevented infection by all six major genotypes of HCV.² This approach holds promise for HCV, but, importantly, it could also potentially be applied to other highly variable pathogens, like HIV.

The challenge doesn’t end with the development of a vaccine—it also needs to be tested. There is no current animal model for HCV, therefore vaccines must be evaluated on people at risk of HCV infection. Dr. Feld’s team is collaborating with researchers across Canada to consider an alternative approach–developing a Controlled Human Infection Model for HCV. This study involves intentionally infecting healthy volunteers with HCV with the goal to test vaccine candidates. Dr. Feld emphasizes that because this unique approach involves infecting healthy people with HCV, extreme care must be taken to ensure safety. Fortunately, if people do not clear the infection on their own, they can be treated with well-tolerated oral antiviral medication. Dr. Feld and his team believe that such an approach will be required to develop an HCV vaccine, and they are working closely with ethicists, virologists, immunologists, and people with lived experience of HCV to design and carry out the CHIM studies efficiently, and, most importantly, safely. 

While HCV is a global health concern that disproportionately impacts nations where non-sterile medical practices are more prevalent than in Canada, the ramifications of HCV infection are felt locally as well. From our biggest cities to the rural north, the consequences of the ongoing opioid epidemic are ever-present, leading to a situation in which new HCV infections continue to outpace cures. Dr. Feld explains that, in addition to new infections, the rise in advanced liver disease from HCV currently observed in Canadian hospitals is likely linked to the lingering impact of the 1970s drug epidemic and the Tainted Blood Scandal of the 1980s (where contaminated blood products infected thousands of Canadians). To stop this scenario from repeating in future generations, it is imperative that an HCV vaccine is developed. Until then, efforts to expand diagnosis and treatment, particularly to marginalized populations who often fall through the cracks of the healthcare system, will be critical. With that, Dr. Feld and the researchers of CanHepC are determined to ensure Canada meets the WHO’s 2030 HCV elimination targets through their combined, ground-breaking research efforts.

References

1. El-Sayed,MH, Feld,JJ.Vaccination at the forefront of the fight against hepatitis B and C.Nat.Rev.Gastroenterol.Hepatol.2022;19(2):87–88.
2. Mosa,AI, Campo,DS, Khudyakov,Y, AbouHaidar,MG, Gehring,AJ, Zahoor,A, Ball,JL, Urbanowicz,RA, Feld,JJ.Polyvalent immunization elicits a synergistic broadly neutralizing immune response to hypervariable region 1 variants of hepatitis C virus.Proc.Natl.Acad.Sci.U.S.A.2023;120(24):e2220294120.