CanHepC is designed to facilitate the establishment and development of inter-institutional, inter-disciplinary, cross-jurisdictional research initiatives. The network is structured around four research cores in addition to two transversal cores dedicated to training and knowledge translation and implementation.
Basic Science Discovery Core
Leader: Dr. Naglaa Shoukry
Although highly effective direct-acting agents (DAAs) will greatly improve clinical outcomes, the need for basic research remains prominent. Development data to assess vaccine delivery and effectiveness in high-risk populations is a strength of our network. In addition, enhancing our understanding of molecular mechanisms underlying HCV pathogenesis and development of hepatocellular carcinoma (HCC) will help identify biomarkers that predict disease progression to help inform decisions on treatment priority. Biomarkers will also be useful to determine if liver injury will reverse and complications like HCC and liver transplant will still occur after successful therapy. Finally, it is possible that resistance to the current DAAs will be a problem. Strategies to rapidly detect resistance will enhance the development of a personalized approach to HCV treatment. This core will focus on the following areas of research:
- Development of prophylactic vaccines against HCV
- Biomarkers of liver disease progression and incidence of HCC
- Impact of treatment on reversing liver disease progression and other pathologies.
Behavioural and Epidemiology Research Core
Leader: Dr. Julie Bruneau
This core will address issues crucial to HCV prevention and care among vulnerable populations. Injection drug use is at the center of the HCV epidemic, accounting for the majority of new HCV cases in Canada. Drug injecting patterns change constantly and vary considerably between settings. Prescription opioid injection has emerged as a major public health concern in both urban and rural areas, and has been associated with transition to heroin use and HCV transmission in some settings, but not others. Likewise, there is an elevated HCV risk in men who have sex with men (MSM), especially among HIV-positive MSM. To enhance our prevention efforts, it is thus crucial to continue monitoring new HCV infections and reinfections in at-risk populations, and examine associated factors. Such data are essential for proper modelling and cost effectiveness studies to inform policies and programs. Moreover, strategies to enhance HCV care in vulnerable populations require addressing key elements that often precede and impede clinical care and treatment, such as stigma, substance use patterns, high risk behaviours, mental health problems, HCV awareness and testing and adapted linkage to HCV care. Administrative databases can inform on population-based outcomes but a comprehensive data collection system is needed to help identify factors that will help optimize HCV prevention and control, and treatment decision-making at the individual and system level in specific sub-populations. This core will focus on the following areas of research:
- Monitoring primary HCV infection and reinfection incidence and associated factors
- Identifying and evaluating prevention strategies to reduce incidence (both primary and reinfection) among at-risk individuals, particularly people who inject drugs (PWID)
- Assessing HCV awareness, screening technologies, and characterizing understudied at-risk populations (e.g. Indigenous people, immigrants, rural young PWID, and HIV+ MSM)
- Evaluating access to care and strategies to enhance linkage between communities and clinics for disengaged and vulnerable populations
- Measuring the long-term impact of HCV treatment and care on injection and non-injection drug use, risk behaviours and HCV reinfection
Clinical Research Core
Leader: Dr. Jordan Feld
Successful clinical trials for HCV DAA therapies have focused only on viral cure (SVR), target highly selected adherent patient populations largely excluding PWID and other marginalized populations, and do not address critically important longer-term clinical outcomes such as end-stage liver disease, HCC, liver transplantation and rates of reinfection. Given the high costs of DAAs, understanding the longer-term health benefits of therapy, will be critical to guide policy. Further, achieving HCV elimination in Canada will require treatment of individuals with minimal or no liver disease who are at high risk of transmitting the virus. Determining the optimal models of care to deliver treatment to vulnerable populations, and carefully documenting reinfection rates and long-term health outcomes in these populations, will be critical to assess the feasibility of this approach. Members of this Network are well poised to address these critical questions, with extensive experience in long-term follow-up studies. Following on the highly successful model of the HIV Clinical Trials Network, the clinical network will also serve as a platform for conducting investigator-initiated clinical trials to answer important questions unlikely to be evaluated by the pharmaceutical industry. This core will focus on the following areas of research:
- Clinical effectiveness of HCV therapy with a focus on short-term (SVR, adherence, toxicity) and long-term (resistance, reinfection) outcomes with comparisons between different clinical populations and models of care
- Assessment of long-term clinical outcomes (HCC, liver transplantation, liver-related mortality, all-cause mortality, regression of fibrosis) in different clinical populations
- Access to care and treatment uptake in different HCV-infected populations and using different models of care delivery
Health System and Policy research core
Leader: Dr. Mel Krajden
This core will provide a strong surveillance, monitoring and analytical infrastructure and support analytical research to address its main objectives. Administrative databases are mostly valuable for monitoring health outcomes at the population level. In addition, linkages with biological, clinical and behavioural data available in the network registries and organized through our data support and methodology will allow an increased capacity to examine issues pertaining to each of the major affected population groups (PWID, HCV/HIV co-infected, baby boomers, immigrants and Indigenous people). Little is known about the proportions of people tested for HCV, linked to care, and treated, also known as the “HCV cascade of care.” Further, although new interferon-free therapies have great potential to reverse the impending wave of HCV-related morbidity and mortality, these regimens will be expensive. Addressing the burden of HCV-related liver disease in Canada will require an understanding of the epidemiological and economic impact of strategies for allocating and optimizing HCV testing and treatment. This information will provide the required empirical evidence to inform HCV clinical management and to develop meaningful HCV health policy. This core will focus on the following areas of research:
- Estimating and monitoring trends in HCV incidence, prevalence and HCV-related liver disease burden in Canada with a focus on the impact of new HCV therapies
- Describing the HCV cascade of care in Canada
- Mathematically modelling the epidemiological impact and cost-effectiveness of strategies for increasing and allocating HCV testing and treatment, including HCV Treatment as Prevention
Knowledge Translation and Implementation
Leader: Daryl Luster
The Knowledge Translation (KT) core is built on the principles of integrated KT, to take advantage of the various partnerships enabled by the Network. The objectives of our research must be informed by the current realities facing HCV patients and healthcare systems and must achieve outcomes that will impact them. Each stage in the research process will be used as an opportunity to create and foster collaboration with knowledge users (KUs). Community-based organizations, very active with vulnerable populations, will enable feasible integration of new knowledge into practice and different communities. Decision makers will help the network to achieve broadly applicable and sustainable health services interventions and population health strategies. We aim to leverage the ability of patient organizations to reach out to patients to facilitate patient-mediated KT strategies.
The ultimate KT goal of the Network is the development of a Canadian Hepatitis C Strategy, based on the concerted effort of researchers, affected communities, healthcare providers, the community sector and decision-makers, and translating evidence-based results emerging from the Network into enhanced and efficient programs, practices, and policies that improve health of HCV-infected individuals. To deliver this Strategy, the Network will prioritize 3 targets and work with specific KUs to develop specific Knowledge-to-Action Framework:
- Primary Care providers and relevant Healthcare professionals – increase their participation in interventions offering testing, clinical management, treatment assessment and follow up among people from priority populations – collaboration with Canadian Association of Hepatology Nurses (CAHN), Canadian Association for the Study of the Liver (CASL)
- Patients and communities – enhance the use of systematic comprehensive screening programs in vulnerable populations, improve awareness and knowledge about testing and treatment options – collaboration with the Canadian Liver Foundation (CLF), CATIE –Canada’s Source for HIV and Hepatitis C information, other organizations and patient partners.
- Decision-makers - to actively provide accurate data to decision-makers to inform the planning and delivery of prevention and disease management options – collaboration with Health Canada
Training and mentorship core
Leader: Dr. Christopher D. Richardson
CanHepC is dedicated to provide transdisciplinary training and mentorship to accelerate the development of critically needed capacity in HCV research. CanHepC is building on the achievements of the National CIHR Research training program in Hepatitis C (NCRTP-HepC), established in 2003, to train the next generation of researchers in all areas related to HCV in Canada using a multidisciplinary approach. Since 2003, a total of 71 trainees and 46 summer students have benefited from the program and their success is recognized worldwide. Some of them became leaders in the field and have now come full circle as independent investigators and co-applicants of this network.
The existing NCRTP-HepC curriculum and trainees is now completely integrated into and remain a central focus of the CanHepC. Click here to learn more about the CanHepC training program.