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

摘要：项目2.风险分层和基于简化磁共振成像的监测 这个翻译项目将首先进一步研究肝细胞癌发病机制的临床意义。 我们描述了这一点，这在AI/AN患者中尤其重要，即HBV型特异性突变。我们 然后将使用我们小组描述的AI/AN特定的肝细胞癌危险因素(包括乙肝病毒基因和基因- 特定突变)，以开发针对AI/AN的肝癌风险计算器，用于肝癌风险分层和基于风险 监视系统。最后，我们将使用肝癌风险计算器来识别高危患者，以进行更密集的治疗 使用简化核磁共振成像的监测战略，这将在试点和可行性随机对照试验中进行测试。该项目将 实现以下具体目标： SA1.阿拉斯加本地人乙肝病毒基因突变在肝细胞癌发生中的作用 患者：确定不同乙肝病毒携带者的HBV型特异性突变的发展 肝细胞癌发生前的基因类型与未发生肝细胞癌的适当对照的比较，以及过度肝细胞癌 与这些突变相关的风险。 SA2.开发并验证患有乙肝或肝硬化的AI/AN患者的“肝细胞癌风险计算器”。 特定于AI/AN患者的人口学预测指标，用于风险分层、识别高危人群 患者和个性化的肝细胞癌监测策略。 SA3.进行简化磁共振成像(AMRI)与非磁共振成像(AMRI)的试点和可行性随机对照试验 超声对200例高危AI/AN患者进行肝癌筛查。 意义重大。该项目将为基于肝细胞癌评估的精确肝细胞癌筛查奠定基础 使用肝癌风险计算器对个体患者进行风险评估，根据患者的肝癌风险对患者进行风险分层，以及 针对不同类别的肝细胞癌风险制定具体的肝细胞癌监测策略。这将被开发和 在随后的P50申请中进一步追查

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