Risk stratification strategies and abbreviated MRI-based surveillance for early detection of HCC in high-risk AI/AN patients

点击翻译按钮获取中文摘要

ABSTRACT: PROJECT 2. Risk Stratification and abbreviated MRI-based surveillance This translational project will first investigate further the clinical significance of an HCC pathogenetic mechanism that we described, which is particularly important in AI/AN patients, i.e. HBV genotype-specific mutations. We will then use AI/AN-specific HCC risk factors described by our group (including HBV genotype and genotype- specific mutations) to develop AI/AN-specific “HCC Risk Calculators” for HCC risk stratification and risk-based surveillance. Finally, we will use HCC Risk Calculators to identify high-risk patients for more intensive surveillance strategies using abbreviated MRI, which will be tested in a pilot and feasibility RCT. The project will accomplish the following specific aims: SA1. Investigate the role of genotype-specific HBV mutations in the development of HCC in Alaska Native patients: Determine the development of HBV genotype-specific mutations in AN patients with different HBV genotypes prior to the occurrence of HCC compared to appropriate controls without HCC, and the excess HCC risk associated with these mutations. SA2. Develop and validate “HCC Risk Calculators” in AI/AN patients with HBV or cirrhosis using biological and demographic predictors specific to AI/AN patients for the purpose of risk stratification, identification of high-risk patients and personalized HCC surveillance strategies. SA3. Perform a pilot and feasibility randomized controlled trial of abbreviated MRI (aMRI) versus ultrasonography (US) for HCC screening in 200 AI/AN patients who have high HCC risk. SIGNIFICANCE. This project will set the foundation for “precision HCC screening” based on estimating HCC risk in individual patients using HCC Risk Calculators, risk stratifying patients according to their HCC risk, and developing specific HCC surveillance strategies for different categories of HCC risk. This will be developed and pursued further in a subsequent P50 application