Monocyte-macrophage activation is associated with nonalcoholic fatty liver disease and liver fibrosis in HIV monoinfection independently of the gut microbiome and bacterial translocation
Monocyte-macrophage activation is associated with nonalcoholic fatty liver disease and liver fibrosis in HIV monoinfection independently of the gut microbiome and bacterial translocation
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单核细胞-巨噬细胞活化与HIV单一感染的非酒精性脂肪肝和肝纤维化相关，独立于肠道微生物组和细菌易位
DOI：
10.1097/qad.0000000000002133
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发表时间：
2019-04-01
期刊：
影响因子：
3.8
通讯作者：
Lemoine, Maud
中科院分区：
文献类型：
--
作者：
Maurice, James B.;Garvey, Lucy;Lemoine, Maud
背景：非酒精性脂肪性肝病（NAFLD）在HIV感染者中很常见。NAFLD的病理生理学和纤维化的发展，在这个population.Objectives：本研究的目的是探讨细菌易位，脂肪组织功能障碍，单核细胞活化和肠道生态失调的患者与HIV单一感染和NAFLD.Methods：活检证实NAFLD和HIV单一感染的病例年龄和性别匹配的HIV阳性和HIV阴性对照。通过ELISA测定细菌易位标志物[脂多糖结合蛋白（LBP）、细菌DNA和脂多糖（LPS）]、脂肪组织功能障碍（瘦素、脂联素）和单核细胞活化（sCD 14和sCD 163）。用免疫组化方法研究巨噬细胞激活的肝脏模式。结果：纳入33例（≥ F2纤维化组n = 16），与HIV阳性组（n = 29）和HIV阴性组（n = 17）相匹配。与HIV阳性对照组相比，NAFLD患者更肥胖（BMI 31.0 +/- 4.4 vs. 24.1 +/- 2.8 kg/m2，P < 0.001），sCD 14、sCD 163水平显著升高，瘦素/脂联素比值更高。>= F2 vs < F2纤维化的病例sCD 14增加（1.4 +/- 0.4 vs. 1.1 +/- 0.3 μ g/ml，P = 0.023）和sCD 163（1.0 +/- 0.3 vs.0.8 +/- 0.3 μ g/ml，P = 0.060），与腰围相关（sCD 14 P = 0.022，sCD 163 P = 0.011）。免疫组化显示肝纤维化患者肝门巨噬细胞簇增加。没有细菌易位或微生物组变化的标志物与NAFLD或fibrosis.Conclusion：NAFLD纤维化阶段在HIV单一感染患者与单核细胞活化的背景下，肥胖，这可能是独立的细菌易位和肠道微生物组。版权所有（C）2019威科医疗集团All rights reserved.
Background: Nonalcoholic fatty liver disease (NAFLD) is common among people living with HIV. There are limited data available on the pathophysiology of NAFLD and the development of fibrosis in this population.Objectives: The aim of this study was to investigate the association of bacterial translocation, adipose tissue dysfunction, monocyte activation and gut dysbiosis in patients with HIV monoinfection and NAFLD.Methods: Cases with biopsy-proven NAFLD and HIV monoinfection were age and sex-matched to HIV-positive and HIV-negative controls. Markers of bacterial translocation [lipopolysaccharide-binding protein (LBP), bacterial DNA and lipopolysaccharide (LPS)], adipose tissue dysfunction (leptin, adiponectin) and monocyte activation (sCD14 and sCD163) were measured by ELISA. Hepatic patterns of macrophage activation were explored with immunohistochemistry. 16 s rRNA sequencing was performed with stool.Results: Thirty-three cases were included (>= F2 fibrosis n = 16), matched to HIV-positive (n = 29) and HIV-negative (n = 17) controls. Cases with NAFLD were more obese (BMI 31.0 +/- 4.4 vs. 24.1 +/- 2.8 kg/m(2), P < 0.001) and had significantly increased levels of sCD14, sCD163 and higher leptin to adiponectin ratio vs. HIV-positive controls. Cases with >= F2 verses < F2 fibrosis had increased sCD14 (1.4 +/- 0.4 vs. 1.1 +/- 0.3 mu g/ml, P = 0.023) and sCD163 (1.0 +/- 0.3 vs. 0.8 +/- 0.3 mu g/ml, P = 0.060), which correlated with waist circumference (sCD14 P = 0.022, sCD163 P = 0.011). Immunohistochemistry showed increased hepatic portal macrophage clusters in patients with fibrosis. No markers of bacterial translocation or changes to the microbiome were associated with NAFLD or fibrosis.Conclusion: NAFLD fibrosis stage in HIV monoinfected patients is associated with monocyte activation in the context of obesity, which may be independent of bacterial translocation and gut microbiome. Copyright (C) 2019 Wolters Kluwer Health, Inc. All rights reserved.