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.

中文翻译：

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促炎性白细胞介素 18 与 HIV 单一感染者的肝脂肪变性和肝酶升高有关

HIV 感染者 (PWH) 患非酒精性脂肪肝 (NAFLD) 的风险增加。白细胞介素 (IL)-18 受炎症小体调节以响应病原体和危险信号，并且与 NAFLD 的发病机制和 HIV 疾病进展有关。我们假设增加的 IL-18 可能与 PWH 中的 NAFLD 和肝损伤有关。这是一项对波士顿地区 125 名 PWH 和 59 名未感染 HIV 的人进行的观察性研究。已知患有乙型肝炎、丙型肝炎和过度饮酒的参与者被排除在外。通过酶联免疫吸附测定法测量血清中的IL-18。通过肝脾计算机断层扫描 (CT) 衰减比评估肝脂质含量。PWH 组的天冬氨酸氨基转移酶 (AST)、丙氨酸氨基转移酶 (ALT) 和 IL-18 水平高于对照组。在 PWH 中，记录₁₀ IL-18 与 log ₁₀ AST ( r  = 0.34, p  = .0001)、log ₁₀ ALT ( r  = 0.33, p  = .0002)、log ₁₀ HIV RNA ( r  = 0.29, p  = .002)、并且与肝脾比负相关（r  = -0.24，p  = .02）。此外，log ₁₀ IL-18 与 log ₁₀甘油三酯相关（r  = 0.26，p  = .003），log ₁₀ MCP-1（单核细胞趋化蛋白-1；r  = 0.33，p  = .0004），log₁₀ caspase-1 ( r  = 0.35, p  < .0001), log ₁₀ LPS ( r  = 0.28, p  = .004)，与高密度脂蛋白负相关 ( r  = -0.28, p  = .002)，以及CD4 ⁺ /CD8 ⁺ T 细胞比率 ( r  = -0.24, p  = .007)。在没有 HIV 的对照组中，log ₁₀ IL-18 也与 log ₁₀ ALT 相关（r  = 0.44，p  = .0005）。调整潜在混杂因素后，IL-18 与 AST ( p  = .004) 和 ALT ( p = .003) 仍然显着，IL-18 与肝脾比之间的关系 ( p  = .02)。PWH 中炎症小体激活增加和随后的单核细胞募集可能有助于 NAFLD 的发展和进展。临床试验注册。NCT00455793。