Mediators of Fatty Liver Disease

Award amount: 125,000.00

Jennifer Price, MD, Recipient

As the prevalence of metabolic syndrome and obesity rises, and as more effective HCV treatments become available, fatty liver disease will likely become a leading cause of liver disease in persons living with HIV. The purpose of this study is to determine the association of metabolic, host genetic, and viral factors with hepatic steatosis (Aim 1) and hepatic fibrosis (Aim 2) in HIV-infected adults with and without HCV-coinfection. We propose to merge data from two NIH-sponsored cohorts, the Women?s Interagency HIV Study (WIHS) and the Study of Visceral Adiposity, HIV, and HCV: Biologic Mediators of Steatosis (VAHH), in order to assemble a unique cohort of men and women, with and without HIV and HCV infections, with state-of-the-art assessment of hepatic steatosis using magnetic resonance spectroscopy and fibrosis using transient elastography. We will directly compare HIV/HCV-coinfected, HIV-monoinfected, HCV-monoinfected, and HIV- and HCV-uninfected individuals to evaluate the relationship between HIV and HCV infections and hepatic steatosis/fibrosis. To address the role of host genetics on steatosis and fibrosis, we will perform genetic testing of the I148M single nucleotide polymorphism (SNP) in the patatin-like phospholipase domain-containing 3 (PNPLA3) gene and other SNPs that have been associated with fatty liver disease. We hypothesize that among HIV-infected individuals, hepatic steatosis will be predominantly mediated by metabolic and genetic (rather than viral) factors. We also hypothesize that visceral obesity, PNPLA3 I148M, and HCV infection will be independently and synergistically associated with increased fibrosis. This study will provide novel insights into the interplay between host genetic and viral factors influencing the development of steatosis and fibrosis among HIVinfected individuals and will lay the groundwork for an NIH K23 to prospectively evaluate factors influencing the natural history of fatty liver disease in the setting of HIV infection.