Metabolic syndrome and obesity are the cornerstones of liver fibrosis in HIV-monoinfected patients

• Published in: AIDS (London) Vol. 31; no. 14; pp. 1955 - 1964
• Main Authors: Lemoine, Maud, Lacombe, Karine, Bastard, Jean P, Sébire, Manuela, Fonquernie, Laurent, Valin, Nadia, Fellahi, Soraya, Capeau, Jacqueline, Girard, Pierre-Marie, Meynard, Jean-Luc
• Format: Journal Article
• Language: English
• Published: England Copyright Wolters Kluwer Health, Inc 10.09.2017
• Subjects: AIDS/HIV; Biomarkers - blood; Cohort Studies; Female; HIV Infections - complications; HIV-1; Humans; Liver - pathology; Liver Cirrhosis - epidemiology; Macrophage Activation; Male; Metabolic Syndrome - complications; Middle Aged; Obesity - complications; Risk Assessment
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/QAD.0000000000001587

BACKGROUND:Metabolic syndrome (MetS) and nonalcoholic fatty liver disease have become a common finding in HIV-infected patients. However, the severity, risk factors and pathogenesis of liver fibrosis in this population have been poorly documented. OBJECTIVES:To assess the impact of MetS on liver fibrosis and analyze the association between MetS, liver fibrosis and markers of adipose tissue and macrophage activation. METHODS:In a matched cohort of HIV-1-monoinfected patients with and without MetS, after exclusion of other causes of liver disease, we assessed liver stiffness measurement and measured levels of serum adipokines, homeostasis model assessment index and soluble CD163 (sCD163) and CD14 as markers of fat, insulin resistance and macrophage/monocyte activation, respectively. RESULTS:A total of 468 HIV-monoinfected individuals were enrolled; 405 (203 with MetS/202 without MetS) were analyzed. Patients with MetS were older and 49% had insulin resistance. The prevalence of significant liver fibrosis (≥F2) was higher in patients with MetS [25.1%, 95% confidence interval (19.3–31.2)] compared with those without MetS [7.9%, (4.6–12.5), P < 0.0001]. In multivariable analysis, obesity [odds ratio3.9 (95% CI 2.1–7.1)] and homeostasis model assessment [1.1 (1.06–1.2)] were independent factors of significant fibrosis and remained associated after adjustment on MetS. Serum levels of adipokines and sCD163 were significantly associated with the degree of liver fibrosis. When adjusted on MetS, leptin and sCD163 remained strongly associated with fibrosis/cirrhosis, whereas HIV parameters and antiretroviral therapy were not. CONCLUSION:In HIV-monoinfected patients, MetS is an important risk factor of liver fibrosis. Adipose tissue and macrophage activation might be key players in the development of liver fibrosis but the exact mechanisms need to be elucidated.