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

摘要 肝硬变是慢性肝病的终末期结果，是一种发病率高和 死亡率正变得越来越普遍。近一半的肝硬变患者 肝脏失代偿，包括肝细胞癌，经常住院 在确诊为肝硬变的5年内。多项研究表明，这些肝硬变并发症 不成比例地影响种族/族裔少数群体和社会经济地位较低的人。 但基本问题仍然没有得到回答，因为只有很少的研究对 形成这些差异的机制。这里提出的研究旨在提供 关于降低肝硬变预后差异的目标的可操作信息。我们会 对假定在以下方面发挥重要作用的多层次因素进行综合评估 在三个衡量肝硬变预后的关键指标中造成种族/民族和自闭症的差异：a) 肝脏失代偿，包括肝细胞癌，b)与肝脏相关的住院，以及c)总存活率。 我们建议进行一项大型、多中心、种族和社会经济多元化的队列研究 来自四个医疗保健系统的肝硬变患者；该项目将结合信息 来自现有的临床数据库、基因组数据和患者的地理空间分析--以及 临床医生-提供无与伦比的个人、人际、 以及社区水平因素对肝硬变预后的种族/民族和SES差异的影响。 拟议的队列包括来自所有种族/民族(黑人、西班牙裔、 亚太岛民)和SES群体。它还涵盖了各种疾病的严重程度。 (从代偿性疾病到晚期失代偿性疾病)，而不是专注于几个 组。我们将揭示已建立的(丙型肝炎病毒、乙肝病毒)的相对贡献 病毒)和新出现的(肥胖、糖尿病)病因风险因素以及危险行为(酒精 用途)对肝硬变预后的差异。我们还将描述有助于 在个人的高位决定因素之间的肝硬变差异(例如，医疗不信任)， 直接或间接的人际关系(如偏见)和社区(如交通工具)水平 通过影响病因或行为危险因素。确定这些根本原因的机制 将确定干预和政策变化的可行目标。我们还将研究一组 使用队列的子集中存储的血清进行遗传单核苷酸多态 了解基因差异(如果有的话)在解释种族/民族差异方面的作用。

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.