Title: Accelerating the Elimination of Hepatitis C in the UK
Funder: Department of Health and Social Care

Abstract: AimTo bring advances in experimental medicine to the clinic to accelerate the elimination of hepatitis C in the UKThe objectives of the work are to:1) Identify ongoing transmission of HCV through implementation of routine next generation viral sequencing in NHS services 2) Develop a clinical network to improve identification and treatment of recent HCV infection and underserved populations 3) Develop diagnostics for rapid delivery at point-of-care to improve linkage to care 4) Combine clinical and sequencing data to identify networks of transmission for targeting interventionWork planned as part of this application will :- Compare two methods for next generation sequencing (NGS) of hepatitis C (those developed by the STOPHCV and ICONIC consortia), against a standardized panel of isolates and existing methods of genotyping and, for the first time, implement one method into NHS practice for routine diagnosis to support identification of transmission networks. - Provide support to other centres wishing to introduce NGS sequencing into their service to develop capacity throughout the NHS. - Establish a multi-centre network to describe the cascade of care of individuals with recent hepatitis C infection. This will initially focus on People living with HIV (PLWH) where there is evidence of ongoing transmission driven by an overlap of high-risk sexual behaviour and injecting drug use. Detailed data will be collected to understand transmission risk behaviours (including sexual behaviours, use of recreational drugs, geographic location, barriers to treatment, linkage to care and treatment and outcomes of therapy, risks of reinfection). - Establish the feasibility of recruiting hepatitis C infected individuals presenting to secondary care into a clinical cohort to identify the proportion of those who are homeless or vulnerably housed and the barriers to accessing care and treatment - Develop new methodologies to diagnose active infection in seropositive individuals to address the challenges in linking newly diagnosed patients to care - For the first time in the UK, use a combination of data from above to describe networks of hepatitis C transmission across different areas and investigate whether transmissions are more likely to be detected at single centres or between centres to inform future interventions.Potential benefits to patients and the NHSThe harmonization of approaches in different clinics towards recent hepatitis C infection will provide a standard of care which will be able to assess the performance of services and ensure the best care for individual patients. There has not until now been a unified effort to bring together clinical and epidemiological data and sequence across a network of clinics to understand transmission of hepatitis C. The information collected has the potential to provide important insights to inform policies for control where data is currently lacking and provide a rational basis for future intervention studies. During the period of this fellowship the relative importance of the marginalised populations that are the focus of this work will increase as hepatitis C treatment become more affordable and it become possible to cure all those individuals engaged in care. There will be a need for a better understanding of where new infections are happening and how to best prevent them. The information generated will provide evidence for new interventions to intervention. Despite scaling up access to treatment for hepatitis C, new infection rates have yet to fall and preventing further infection will save the costs of care and treatment to the NHS. This Professorship will enable the world leading scientific advances made by the UK HCV community to benefit all those with hepatitis and accelerate the elimination of HCV in the UK.

Lay abstract: This Research Professorship will bring advances in experimental medicine to the clinic to accelerate the elimination of hepatitis C in the UK. Background Hepatitis C is a virus which can lead to scarring of the liver (cirrhosis) and liver cancer. It is a leading cause of death globally and in the UK it is one of the leading reasons for liver transplantation. It is curable but, until recently, treatment was limited by the need for weekly injections of interferon, prolonged treatment, high failure rates and significant side-effects (including flu-like symptoms). There has been a revolution in hepatitis C treatment over the last 3 years with new tablet-only therapies now available taken for between 8 and 12 weeks. They do not require interferon, have much better side-effect profiles and higher cure rates. These rapid advances are leading to serious discussion about the elimination of hepatitis C. Ambitious targets have been set by the WHO to scale up treatment to 80% of those in need by 2030. At the moment the cost of ddrug is a major barrier to treating all those in care (despite the NHS committing over 200m a year). Over the next 5 years this will change and there will need to be a greater emphasis on finding and curing those who are either not aware of their infection and/or not engaged with services. In particular, if the infection is to be eliminated, new infections will need to be stopped through identification and treatment of those at risk of passing it on. Proposed work This project looks ahead to this next phase of the response to hepatitis C and will allow identification and treatment those at risk of passing on hepatitis C, ready for a time when availability of treatment will not be the limiting factor in patients accessing care. To do this will require: (i) New tests to be used routinely within NHS laboratories allowing more detailed study of the virus. Current methods for analysing hepatitis C virus only look at a small part of the virus and don't provide enough detail to work out which individuals might have transmitted the virus to each other. Methods for doing this have been evaluated by two groups in the UK; STOPHCV and ICONIC. This project will compare these two different approaches and implement the one best able to be deployed sustainably in the NHS to detect ongoing transmission. (ii) Establishing a common approach to the identification and management of new and recent infections within NHS services by ensuring data is collected to identify networks of individuals where new infections are occurring. In particular, there are number of high risk groups for hepatitis C infection which are harder to engage in care and are important sources for new infections. This work will focus on two such groups, those with HIV infection and those who are homeless or vulnerably housed. Detailed demographic, clinical and behavioral data will be captured to understand these groups in more detail. (iii) New approaches to diagnosis to ensure that when individuals are first diagnosed with hepatitis C infection they are able to access care and treatment quickly. One of the current challenges is the need for tests carried out in central laboratories, where results may take days to come back. This project will develop a new technology which has the potential to bridge this gap by providing a test immediately, regardless of the setting. The device can operate on a USB stick to detect HIV and will be developed here to detect hepatitis C. (iv) Defining networks of individuals transmitting hepatitis C virus. By combining information on both individuals with recent hepatitis and more detailed information on their virus from new sequencing methods it will be possible to build a picture of how virus is being transmitted. Such data can be used to predict and test novel ways to tackle ongoing new infections. Patients and patient groups have been involved in prioritizing the chosen areas of work for this proposal. The evolving design of the work in sections (ii) and (iv) above will also be in close co-operation with patient groups to ensure that the information collected can be of maximal value to eliminating hepatitis C whilst ensuring confidentiality is maintained. Results from this work will be disseminated through published, peer-reviewed papers, presentations at clinical /scientific meetings and policy meetings within the UK. Patient groups and charities will be an important route for disseminating findings to help generate a wider discussion around the elimination of hepatitis C.

Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION