Hepatitis B virus (HBV) infection is globally the most common and serious viral infection of the liver, causing premature deaths from liver diseases or liver cancer. Chronic hepatitis B (CHB) infection and liver cancer caused by HBV among Asian Americans is one of the most serious—but frequently neglected—health disparity issues in the U.S. Hepatocarcinogenesis from HBV infection to hepatocellular carcinoma (HCC) development has been increasingly recognized as a multifactorial, multi-level and multi-step process. Less is known about the multiple factors and the underlying mechanisms responsible for chronic liver disease progression in high risk Asian Americans. Evolving models of liver disease posit a strong role for virus, chronic inflammation and oxidative DNA damage. Co-factors that may influence these disease processes include exogenous and endogenous factors. The application of a multi-level framework, however, is relatively new in the study of chronic liver disease progression (e.g., CHB phenotype, liver disease severity) among CHB patients. Moreover, there is great variance in the hepatic disease progress among CHB patients, and the psychosocial factors contributing to or responsible for biological system impairment have not been identified. The goal of this study is to longitudinally examine the multiple pathways to disparities in chronic liver disease progression using two unique clinic-based patient cohorts of CHB Korean Americans receiving care from Korean-American hepatologists. We will recruit and enroll 600 Korean American CHB patients. Medical chart review, structured patient interviews, biomarkers, qualitative, and geo-spatially referenced data will be integrated to explore multi-level models of liver disease progression over a 10- year clinical window, within a group at high risk for adverse outcomes. The specific aims are: (1) to estimate the prevalence of CHB phenotypes and liver disease severity, and associated covariates at the initial visit; (2) identify how multiple factors (e.g., social environmental, psychosocial, behavioral, clinical and biological attributes) are associated with variation in liver disease progression; (3) to examine the moderating and mediating effects of these factors on the relationship between CHB phenotypes and adverse liver disease outcomes (e.g., HCC); and (4) to understand care-seeking behaviors and dynamics of care within an ethnically concordant liver disease care model using an explanatory mixed methods approach. Finally, comparison to clinical data from large CHB cohorts in US and Korea will strengthen generalizability. Insights gained from this proposed study will provide the groundwork to understand the multi-level and multi-step process of chronic liver disease and liver cancer among high risk population with CHB patients, and develop potential interventions at multiple levels (policy, social-behavioral and clinical) to reduce disparities in liver disease progression.