Duarte Maria J, Tien Phyllis C, Kardashian Ani, Ma Yifei, Hunt Peter, Kuniholm Mark H, Floris-Moore Michelle, Fischl Margaret A, French Audrey L, Topper Elizabeth, Konkle-Parker Deborah, Minkoff Howard, Ofotokun Ighovwerha, Plankey Michael, Sharma Anjali, Price Jennifer C
Division of Gastroenterology and Hepatology, Department of Medicine, University of California.
Department of Medicine, University of California, San Francisco and Department of Veterans Affairs Medical Center.
AIDS. 2025 Jul 15;39(9):1185-1190. doi: 10.1097/QAD.0000000000004189. Epub 2025 Mar 24.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent in people living with HIV (PWH). Gut microbial translocation and gut damage may play a role in MASLD pathogenesis. We determined associations of circulating biomarkers of translocation and gut damage with hepatic steatosis and fibrosis in a large U.S. cohort of women with HIV (WWH) and without HIV.
Vibration controlled transient elastography (VCTE) was conducted from 2013 to 2018 among 854 WWH and 349 women without HIV. Serum biomarkers were measured within 6 months of the VCTE: kynurenine to tryptophan (KT) ratio, intestinal fatty acid binding protein (I-FABP), and immune activation markers soluble CD14 (sCD14) and soluble CD163 (sCD163).
We used multivariable linear regression to evaluate independent associations of each biomarker, HIV serostatus, and demographic, metabolic, and HIV-specific covariates with hepatic steatosis [controlled attenuation parameter (CAP)] and fibrosis [liver stiffness (LS)].
In multivariable analysis, increasing in KT ratio was associated with a 6 dB/m lower CAP and 6% higher LS, and sCD14 with a 5 dB/m lower CAP and 8% higher LS. sCD163 was not associated with CAP but was associated with a 12.5% higher LS value. I-FABP was not associated with either CAP or LS values.
Higher KT ratio, sCD14, and sCD163 were associated with increased hepatic fibrosis but not steatosis. In fact, higher KT ratio and sCD14 were associated with decreased steatosis. This suggests that microbial translocation and gut damage may contribute to the pathogenesis of fibrosis in WWH in a mechanism unrelated to increased steatosis.
代谢功能障碍相关脂肪性肝病（MASLD）在HIV感染者（PWH）中高度流行。肠道微生物易位和肠道损伤可能在MASLD发病机制中起作用。我们在美国一个大型HIV感染女性（WWH）和未感染HIV女性队列中，确定了易位和肠道损伤的循环生物标志物与肝脂肪变性和肝纤维化之间的关联。
2013年至2018年期间，对854名WWH和349名未感染HIV的女性进行了振动控制瞬时弹性成像（VCTE）检查。在VCTE检查后6个月内检测血清生物标志物：犬尿氨酸与色氨酸（KT）比值、肠脂肪酸结合蛋白（I-FABP）以及免疫激活标志物可溶性CD14（sCD14）和可溶性CD163（sCD163）。
我们使用多变量线性回归来评估每种生物标志物、HIV血清学状态以及人口统计学、代谢和HIV特异性协变量与肝脂肪变性[受控衰减参数（CAP）]和肝纤维化[肝脏硬度（LS）]之间的独立关联。
在多变量分析中，KT比值升高与CAP降低6 dB/m和LS升高6%相关，sCD14与CAP降低5 dB/m和LS升高8%相关。sCD163与CAP无关，但与LS值升高12.5%相关。I-FABP与CAP或LS值均无关。
较高的KT比值、sCD14和sCD163与肝纤维化增加相关，但与脂肪变性无关。事实上，较高的KT比值和sCD14与脂肪变性降低相关。这表明微生物易位和肠道损伤可能通过一种与脂肪变性增加无关的机制，促成WWH中肝纤维化的发病机制。
