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

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.