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

摘要：项目2。风险分层和简化的基于MRI的监测 这个翻译项目将首先进一步研究肝癌发病机制的临床意义 这在AI/AN患者中特别重要，即HBV基因型特异性突变。我们 然后将使用我们小组描述的AI/AN特异性HCC风险因素（包括HBV基因型和基因型- 特定突变）开发AI/AN特异性“HCC风险计算器”，用于HCC风险分层和基于风险的 监视最后，我们将使用HCC风险计算器来识别高危患者， 使用简化MRI的监测策略，将在试点和可行性RCT中进行测试。该项目将 实现以下具体目标： SA 1.研究基因型特异性HBV突变在阿拉斯加原住民HCC发生中的作用 患者：确定不同HBV感染的AN患者中HBV基因型特异性突变的发生情况 与没有HCC的适当对照相比，HCC发生前的基因型， 与这些突变相关的风险。 SA 2.使用生物学和生物学方法，在患有HBV或肝硬化的AI/AN患者中开发并验证“HCC风险计算器”， 特定于AI/AN患者的人口统计学预测因素，用于风险分层，识别高风险 患者和个性化HCC监测策略。 SA 3.对简化MRI（aMRI）与 在200例具有高HCC风险的AI/AN患者中进行超声（US）检查以进行HCC筛查。 意义该项目将为基于估计HCC的“精确HCC筛查”奠定基础 使用HCC风险计算器评估个体患者的风险，根据患者的HCC风险对患者进行风险分层，以及 针对不同类别的HCC风险制定具体的HCC监测策略。这将是发展和 在随后的P50申请中进一步追求

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