Biosocial Determinants of Health Among Patients with Chronic Liver Disease and Liver Cancer

Metabolic disorders and chronic liver disease (CLD) play crucial roles in the development and progression of liver cancer (LC). Since the ethnic minority population increasingly suffers from CLD and LC, it is vital to understand the biosocial factors contributing to CLD and LC. The 'All of Us' database, with significant participation from minority populations, provides a valuable tool for studies in different racial/ethnic groups. Using different databases, including the 'All of Us' and 'The Cancer Genome Atlas', this study aimed to understand the biosocial factors contributing to CLD and LC.

Using 'All of Us' data, confounding factors like the lack of immunization, comorbidities, and socioeconomic status (SES) barriers were analyzed in a cohort of 33767 CLD [non-alcoholic fatty liver disease, alcoholic liver disease, and Hepatitis B and C] patients. Among the 556 LC patients in the 'All of Us' database, 92% had CLD. Since hypoxanthine is known to be increased in the urine of LC patients, purine metabolic pathway genes were analyzed using different databases and validated using publicly available RNASeq data.

We identified several confounding factors associated with CLD in Hispanic (HA) and African American (AA) populations compared to the non-Hispanic White (NHW) populations. HA and AA CLD patients suffer from high SES barriers. While most of the genes related to the purine metabolic pathway were upregulated in LC, xanthine dehydrogenase (XDH), which converts hypoxanthine to uric acid, showed a downregulation in the tumor compared to the normal tissues. The TCGA data among different racial/ethnic groups showed that only in Asian (AN) LC tumors the XDH expression was significantly lower compared to the NHW. The decreased XDH mRNA expression in AN LC compared to benign tissues was further validated using publicly available RNAseq datasets. Survival analysis confirmed poor overall survival among the AN LC patients with lower XDH expression in their tumors.

Our study identified several confounding factors contributing to the minority CLD population. This study also identified decreased XDH expression as a critical metabolic alteration that has clinical significance in AN LC patients.