Food Insecurity and Diet Quality: Effects on Liver Disease in People with HIV

University Of Southern California, Los Angeles CA

Investigators

Abstract

ABSTRACT Liver disease is a leading cause of morbidity and mortality among people with HIV (PWH) driven by high rates of metabolic dysfunction-associated steatotic liver disease. Recently, food insecurity, or the limited or uncertain availability of nutritionally adequate foods or the inability to acquire acceptable foods in socially acceptable ways, has emerged as a risk factor for liver disease in people with and without HIV. Women with HIV are particularly susceptible to food insecurity due to competing demands as caregivers and lack of control over household resources. We have shown that food insecurity is associated with greater steatohepatitis and liver fibrosis, but not with steatosis, in PWH, suggesting that factors besides steatosis mediate this association. Our central hypothesis is that poor diet quality due to food insecurity leads to immune activation, which in the setting of HIV accelerates steatohepatitis and fibrosis progression. The scientific objective of this proposal is to identify the mechanisms that underlie the associations between food insecurity, diet quality, and liver disease progression in PWH. To address these knowledge gaps, we will leverage a robust longitudinal cohort, the Multicenter AIDS Cohort Study/Women’s Interagency HIV Study Combined Cohort Study (MWCCS), which includes serial food insecurity measures, comprehensive 24-hour diet quality recall surveys, immune activation biomarkers, and vibration controlled transient elastography-measured steatohepatitis and fibrosis. The scientific aims are to (1) examine the association of persistent food insecurity and diet quality with liver disease progression (2) determine the contribution of immune activation to the association of food insecurity with liver disease and (3) identify specific dietary factors that influence the relationship of food insecurity and immune activation in people with or at risk for HIV. This K23 will provide key training in (1) nutrition-specific content expertise and skills in rigorous diet quality measures, (2) complex biostatistical methods for longitudinal data and mediation analyses, (3) expertise in measures of immune activation in liver disease and HIV, and (4) career development at the intersection of hepatology and nutrition, which will be achieved through formal courses, workshops, didactics, hands-on experience, and structured mentorship. These scientific aims and training goals are made possible by a rich scientific environment at the University of Southern California, access to a unique prospective multicenter data set (MWCCS), and a strong multidisciplinary mentorship team consisting of Dr. Terrault (liver disease, clinical and translational studies), Dr. Goran (nutrition), Dr. Price (HIV and liver disease, immunology), and Dr. Mack (advanced biostatistics). This research will set the stage for an R01 proposal to develop a dynamic risk score that incorporates the contribution of diet quality through clinical and immunologic biomarkers to predict changes in liver disease over time. In summary, the proposed multidisciplinary team, scientific aims, and career development goals will foster Dr. Kardashian’s transition to a successful independent investigator and guide in the development of interventions that will halt the progression of liver disease in vulnerable populations.