Pro-Inflammatory Interleukin-18 is Associated with Hepatic Steatosis and Elevated Liver Enzymes in People with HIV Monoinfection

People with HIV (PWH) are at an increased risk of developing nonalcoholic fatty liver disease (NAFLD). Interleukin (IL)-18 is regulated by inflammasomes in response to pathogens and danger signals and has been implicated in both the pathogenesis of NAFLD and HIV disease progression. We hypothesized that increased IL-18 may be associated with NAFLD and liver injury in PWH. This was an observational study of 125 PWH and 59 individuals without HIV in the Boston area. Participants with known hepatitis B, hepatitis C, and excessive alcohol use were excluded. IL-18 was measured in serum by enzyme-linked immunosorbent assay. Liver lipid content was assessed by liver-to-spleen computed tomography (CT) attenuation ratio. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and IL-18 levels were higher in PWH than in controls. In PWH, log₁₀ IL-18 was associated with log₁₀AST (r = 0.34, p = .0001), log₁₀ALT (r = 0.33, p = .0002), log₁₀HIV RNA (r = 0.29, p = .002), and inversely associated with liver-to-spleen ratio (r = -0.24, p = .02). In addition, log₁₀ IL-18 was associated with log₁₀ triglycerides (r = 0.26, p = .003), log₁₀ MCP-1 (monocyte chemoattractant protein-1; r = 0.33, p = .0004), log₁₀caspase-1 (r = 0.35, p < .0001), log₁₀LPS (r = 0.28, p = .004), and inversely associated with high-density lipoprotein (r = -0.28, p = .002), and CD4⁺/CD8⁺ T cell ratio (r = -0.24, p = .007). In controls without HIV, log₁₀ IL-18 was also associated with log₁₀ALT (r = 0.44, p = .0005). After adjusting for potential confounders, the relationships between IL-18 and AST (p = .004) and ALT (p = .003) remained significant, and the relationship between IL-18 and liver-to-spleen ratio (p = .02). Increased inflammasome activation and subsequent monocyte recruitment in PWH may contribute to the development and progression of NAFLD. Clinical Trials Registration. NCT00455793.