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Background: Metabolic syndrome (MetS) has 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.
From a matched cohort of HIV-monoinfected patients with and without MetS, this study aimed 1) to assess the impact of MetS on the prevalence and severity of liver fibrosis and 2) to analyze the association between liver fibrosis and markers of adipose tissue, insulin resistance and macrophage activation.
Methods: Patients with immune-controlled HIV-1 infection under antiviral therapy (ART) were enrolled in the following exposed-unexposed study. The exposure was defined by the presence of MetS according to international criteria after exclusion of all other causes of chronic liver disease. Fibrosis was assessed using transient elastography (Fibroscan). Adipokines, HOMA index and soluble CD163 and CD14 were measured as markers of fat mass, insulin resistance and macrophage/monocyte activation, respectively.
Results: 468 HIV-monoinfected individuals were enrolled (male (89%), mean age 53 (9) years, mean BMI 24.6 (5.3) kg/m2); 246 with MetS and 222 without MetS. Patients with MetS were older and 49% of them had insulin resistance i.e HOMA-IR≥2.5 (compared to 8.5% in patients without MetS). The mean value (SD) of LSM was 5.6 (2.2) kPa with a minimum and maximum value of 2.4 and 17.1 kPa. Mean LSM was higher in patients with MetS compared to those without MetS [6.3 (2.6) versus 4.9 (1.5) kPa, p< 0.0001]. In multivariable analysis, obesity (OR: 3.9 (IC95% 2.1-7.1)) and insulin resistance (1.1 (1.06-1.2)) were independent factors of significant fibrosis (≥F2) 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 to fibrosis. HIV parameters and ART regimen were not associated fibrosis.
Conclusions: In HIV-monoinfected patients, MetS is an important risk factor of liver fibrosis. Obesity and insulin resistance are key factors in the development of liver fibrosis independently of HIV infection parameters. Adipose tissue and macrophage activation certainly play an important role in the development of fibrosis in HIV monoinfected patients but the exact mechanisms need to be elucidated.