ABSTRACT
Purpose: The overarching goal of this project is to reduce HCC-related morbidity and mortality in persons with chronic hepatitis C (CHC) who have been virologically cured by direct acting antivirals (DAAs). Aims: 1) Examine determinants of HCC in virologically cured patients and develop a risk prediction model for HCC;2) Conduct a virtual clinical trial using a mathematical model of the natural history of HCC to evaluate benefits vs harms of HCC surveillance;3) Develop an online HCC Simulator. Design: Using cause-specific Cox proportional hazard models for competing risks, we will identify risk factors in a retrospective cohort study of >100,000 patients with DAA-induced SVR. For dynamic risk prediction of HCC, we will use the landmark Cox model. We will use a mathematical model to simulate a virtual trial comparing long-term effectiveness of no surveillance vs routine surveillance. Finally, we will develop an interactive decision support tool. Progress: The project is on target to be completed by 09/30/2022. Findings: 19 predictors for HCC were identified, with the nature of predictor variables changing over time. Metabolic traits predicted HCC;however, viral factors (HCV genotype) was no longer predictive at 24 months after cure. A Mathematical model of the natural history of HCC in DAA-cured CHC patients was developed that led the team to conclude that the burden of HCC will shift from viremic to virologically cured CHC patients, and to older populations. These findings are reported in a manuscript that was accepted by JAMA Network Open and is currently in press.