Title: StraTified Medicine Research to Support Hepatocellular Carcinoma ScReening DecIsions for HCV Cirrhosis PatiEnts after Sustained Viral Response (THRIVE-SVR)
Funder: Medical Research Foundation

Abstract: Liver cirrhosis is a major milestone in the natural history of chronic Hepatitis C Virus (HCV) infection. Achievement of a Sustained Viral Response (SVR) via antiviral therapy improves prognosis for HCV cirrhosis patients considerably. But it is not a panacea; after SVR, individuals with cirrhosis still exhibit a high rate of hepatocellular carcinoma occurrence of approximately 1.0-2.5 events per 100 person years. Survival following HCC occurrence is poor overall, with most patients not surviving beyond 5 years. As a result, HCC severely comprises life expectancy for HCV cirrhosis patients after SVR, and limits the benefits of SVR achievement. Although overall survival following HCC diagnosis is poor, it is also highly variable. If HCC is detected at a very early stage (i.e. single nodule less <2cm), five-year survival exceeds 70%. The benefit of SVR achievement for cirrhosis depends therefore on the early HCC detection initiatives in place for this population. Existing standard-of-care Is to screen all cirrhosis SVR patients every six months for HCC (via abdominal ultrasound examination ± alpha fetoprotein measurement). This generic "one-size-fits-all” approach has major weaknesses, including low compliance, infrequent early detection, and high number of false-positive findings. A precision-medicine approach, where clinicians tailor screening decisions to a patient's individual characteristics, could improve patient outcomes immeasurably. This SURVIVE study will help clinicians to stratify cirrhosis SVR patients, according to expected HCC screening benefit. HYPOTHESIS: The hypothesis underpinning this study is that there is substantial variability in the benefits that cirrhosis SVR patients stand to gain from biannual HCC screening. If this hypothesis is correct, then shifting towards an individualised HCC screening program could improve patient outcomes considerably. AIMS: The.SURVIVE study has four main aims. To: 1) Describe population-level changes in the demand/eligibility for HCC screening at post-SVR stage. 2) Quantify adherence to standard-of-care biannual HCC screening for post-SVR cirrhosis patients. 3). Examine individual-level factors that influence benefit of biannual screening, including risk of HCC occurrence, host genetic factors, and non-HCC competing mortality risk. 4) Generate a decision model that estimates median survival benefit conferred via HCC biannual screening, according to patient characteristics. METHODS: I will perform innovative statistical analyses on a strategic set of large and unparalleled HCV data sets from the UK and beyond. These datasets include the Hepatitis C Research UK study (N=2,700 cirrhosis SVR patients); the STOP-HCV cirrhosis study (N=1,255 HCV cirrhosis patients); Scottish cirrhosis SVR enhanced dataset (N=874 cirrhosis SVR patients); Scottish population datasets.(N=>30,000 HCV patient records) and British Columbia HCV population datasets (N=>50,000 HCV patient records). Together, these datasets provide host genomic data, record-linkage data to diverse national registries, and detailed clinical data -all at an individual patient-level. Following analysis of these datasets, we will create a microsimulation. Markov model that computes the expected number of life years gained through HCC screening for a patient with a given set of characteristics at SVR achievement. IMPACT: The SURIVAL study will support progress towards an individualised approach to HCC screening - thus, maximising the benefit of SVR achievement for HCV cirrhosis patients.


Research activity codes: 4.4 POPULATION SCREENING;8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: ORAL AND GASTROINTESTINAL