Multi-level Evaluation of Racial/ethnic Disparities in Liver Disease Outcomes

摘要 肝硬化-慢性肝病的终末期结果-是一种发病率高的病症， 死亡率变得越来越普遍。几乎一半的肝硬化患者 肝功能失代偿，包括肝细胞癌（HCC），频繁住院 肝硬化诊断后5年内。一些研究表明，这些肝硬化并发症 对种族/族裔少数群体和社会经济地位低的人的影响不成比例。 但是，鉴于只有少数研究调查了 这些差异背后的机制。本研究旨在提供 关于减少肝硬化预后差异的目标的可操作信息。我们将 对假设起重要作用的多层次因素进行综合评价， 在肝硬化预后的三个关键指标中引起种族/民族和SES差异：a） 肝失代偿，包括HCC，B）肝脏相关住院，和c）总生存期。 我们提出了一个大型的，多中心的，种族和社会经济多样化的队列研究， 肝硬化患者从四个医疗保健系统招募;该项目将联合收割机信息 根据现有的临床数据库、基因组数据以及患者和 临床医生-调查提供无与伦比的信息的作用，个人，人际， 和社区水平因素在肝硬化预后中的种族/民族和SES差异。 拟议的队列包括来自所有种族/民族的代表性群体（黑人，西班牙裔， 亚太岛民）和社会经济地位群体。它还涵盖了疾病严重程度的全部范围 (from补偿到晚期失代偿性疾病），而不是专注于少数 组我们将揭示建立（丙型肝炎病毒，乙型肝炎B）的相对贡献 病毒）和新出现的（肥胖、糖尿病）病因风险因素以及风险行为（酒精 使用）对肝硬化预后的影响。我们还将描述有助于 个体的高阶决定因素之间的肝硬化差异（例如，医学上的不信任）， 人际（例如，偏见），和社区（例如，交通工具），直接或 通过影响病因学或行为风险因素。确定这些根本原因机制 将确定可采取行动的干预目标和政策变化。我们还将研究一组 使用所述组群的子集中的储存血清进行遗传单核苷酸多态性， 理解遗传差异的作用，如果有的话，在解释种族/民族差异。

ABSTRACT Cirrhosis – the end-stage result of chronic liver disease – is a condition with high morbidity and mortality that is becoming increasingly common. Nearly half of all patients with cirrhosis develop hepatic decompensation including hepatocellular cancer (HCC), with frequent hospitalization within 5 years of cirrhosis diagnosis. Several studies show that these cirrhosis complications disproportionately affect racial/ethnic minorities and persons of low socioeconomic status (SES). But fundamental questions remain unanswered given that only few studies investigated the mechanisms that underlie these disparities. The research proposed here aims to provide actionable information on what to target to reduce cirrhosis prognosis disparities. We will conduct a comprehensive evaluation of multilevel factors hypothesized to play important roles in causing racial/ethnic and SES disparities in three key measures of cirrhosis prognosis: a) hepatic decompensation, including HCC, b) liver-related hospitalization, and c) overall survival. We propose a large, multicenter, racially and socio-economically diverse cohort study of cirrhosis patients enrolled from four healthcare systems; the project will combine information from existing clinical databases, genomic data, and geospatial analyses with patient- and clinician- surveys to provide unparalleled information about the role of individual, interpersonal, and community-level factors in the racial/ethnic and SES disparities in cirrhosis prognosis. The proposed cohort includes representative groups from all racial/ethnic (blacks, Hispanics, Asian-Pacific Islanders) and SES groups. It also spans the full spectrum of disease severity (from compensated to advanced decompensated disease), rather than focusing on a few groups. We will uncover the relative contributions of established (hepatitis C virus, hepatitis B virus) and emerging (obesity, diabetes) etiological risk factors as well as risk behaviors (alcohol use) to cirrhosis prognosis disparities. We will also characterize pathways that contribute to cirrhosis disparities among the high order determinants at the individual (e.g., medical mistrust), interpersonal (e.g., bias), and community (e.g., access to transportation) levels either directly or by affecting etiological or behavioral risk factors. Identification of these root cause mechanisms will identify actionable targets for intervention and policy change. We will also examine a set of genetic single nucleotide polymorphisms using stored sera in a subset of the cohort to understand the role of genetic differences, if any, in explaining racial/ethnic disparities.