Dr. Carla Coffin

https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=520510&lang=en

The hepatitis B virus (HBV) is a major cause of liver disease and liver cancer worldwide. Most people missed getting the vaccine and acquire the virus as infants or young children. Due to the young age of exposure, their immune system does not recognize the virus, they are unable to clear infection and develop "chronic hepatitis B" (CHB). The HBV hides inside the liver life-long and some can develop severe liver disease and liver scarring (i.e., cirrhosis). However, a very small number of people (one out of every 100 per year with CHB), for unclear reasons, are able to successfully clear the HBV such that it is no longer detectable using clinical tests. These people do not need treatment and have achieved a so called "functional cure". Expanding functional cure to the other 99% of individuals is urgently needed because it reduces the risk of liver disease and eliminates the need for life-long expensive treatment. In this study, we will enroll individuals who have achieved a functional cure and compare them to people who still have chronic hepatitis B. We will analyze their blood and liver immune cells for special markers that will help us understand why some (i.e., only 1/100 per year) achieve functional cure. We will combine this data with clinical information and, using standard research methods and artificial intelligence (AI) approaches, find out how the body controls HBV. Finally, we will use liver cells grown in a lab dish, as well as woodchucks infected with a closely related virus (woodchuck hepatitis virus), to understand what factors inside the liver cell can help clear the virus. Identification of these factors can be used to develop improved treatments for hepatitis B. Our team includes experts in hepatitis B, liver and infectious disease specialists, veterinarians, scientists, artificial intelligence experts, patients and community partners that not only help achieve project goals but have enormous potential to advance understanding and care of HBV infection.

https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=450767&lang=en

The hepatitis B virus (HBV) is a major cause of severe liver disease worldwide, including cirrhosis and liver cancer. There are drugs that can control the virus but they do not cure chronic infection. There is a need for greater understanding of the immune response after exposure to virus and in the early acute infection and during long-term chronic infection in order to develop better therapies. Some subspecies of woodchucks (i.e., groundhogs) can be infected with woodchuck hepatitis virus (WHV) a cousin of the HBV, and also develop hepatitis (liver inflammation) and associated liver cancer similar to people. WHV infection in woodchucks is a valuable model helping to understand how liver disease and cancer develops. This animal model is also important for testing of new antiviral drugs. Until now, most assessments of the immune response to HBV infection and to treatment were done by evaluating surrogate markers in blood. We will use well-established conventional tests along with advanced live cell imaging within the liver to assess in real time the immune response to early and long-term WHV infection and after treatment with an antiviral drugs. Our team are experts in liver disease, virology, HBV pathogenesis, in the woodchuck HBV model, woodchuck husbandry, and in using live cell imaging. We will assess, for the first time, virus-cell and cell-cell interactions inside the living liver in response to virus infection, in different stages of liver disease and during anti-viral treatment. This study will ultimately contribute to the development of new treatments aiming to achieve a cure for chronic hepatitis B and complete protection against liver cancer caused by the HBV.

https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=453439&lang=en

The hepatitis B virus (HBV) is the leading global cause of end-stage liver disease, cirrhosis and hepatocellular carcinoma (HCC or primary liver cancer). The management of hepatitis B is often complex and depends upon identifying patients at risk, appropriate diagnostic workup, treatment and follow-up. CHB affects ~260,000 Canadians but disease prevalence and the burden of associated liver disease is expected to increase due to the impact of immigration and an aging population. Despite the availability of potent oral antiviral therapy, persons living with HBV remain at risk for progressive liver disease due to suboptimum linkage to care and low treatment uptake. There is an urgent need for systematic research to identify gaps in the HBV care continuum, improve access to therapy and reduce the risk of HBV-related end-stage liver disease. The Canadian HBV Network is well-established with key infrastructure to help improve the HBV care continuum in Canada. This catalyst grant funding will spearhead an initiative to determine barriers in the linkage to HBV care and access to treatment in patients followed by the Canadian HBV Network. We will (i) conduct a pilot study to describe diagnostic workup, referral patterns, the proportion referred to tertiary care, and those who receive HBV antiviral treatment, (ii) conduct survey studies and focus groups of patients, primary care providers and hepatitis B specialists to inform development of strategies that facilitate access to care and treatment and (iii) develop working groups to inform a larger team grant to enhance collaborations on HBV research, training and improve access to care for hepatitis B in Canada. The PI and co-PIs can engage patients and stakeholders through established collaborations, and have expertise in hepatitis B and/or required research methodology. Our studies will help understand and predict the risk of liver disease related to hepatitis B an often devastating liver disease

https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=495600&lang=en

https://ctnplus.ca/our-people/carla-coffin-2/

Over 30 years, the CIHR Canadian HIV Trials Network (CTN) has built a world-class national network enabling Canadian researchers, healthcare providers and community members to collaborate locally and internationally to lead impactful, outcomes-based clinical research in HIV, hepatitis C, syphilis and other sexually transmitted and blood-borne infections (STBBIs) and train the next generation of researchers. Despite tremendous progress, important disparities across regions and populations remain. There are also many opportunities to develop new technologies, models of care and curative therapies. Aligned with the CIHR HIV/AIDS and STBBI Research Initiative, we present our proposal to restructure the CTN. At its foundation are five Interdisciplinary Clinical Trials Research Teams (Atlantic, Quebec, Ontario, Prairies, and British Columbia/Yukon) that will respond to local priorities, ensure meaningful community engagement, and offer equitable access to research for all populations. We will foster innovative pan-Canadian trials through science accelerators focused on Prevention, Treatment/Management, and Cure, informed by regional teams and people with lived/living experience including Indigenous groups. A National Coordinating Centre will provide critical infrastructure to promote network objectives and accelerate research. A Community-Centred Knowledge Mobilization (KM) Hub will support all CTN members to create high-quality, effective KM products to share research outputs using culturally safe approaches to diverse stakeholders. Strong governance will ensure equity, diversity and inclusion in decision making and engagement with national and international networks. Building on a track record of success, the reimagined CTN+ will strengthen capacity for STBBI trials in Canada, mobilize research knowledge among stakeholders, improve health equity for marginalized populations, and meaningfully advance commitments towards Truth and Reconciliation with Indigenous Peoples.