Markers of Monocyte Activation, Inflammation, and Microbial Translocation Are Associated with Liver Fibrosis in Alcohol Use Disorder

Abstract

Background: The association between markers of inflammation (interleukin (IL)-6 and IL-10), monocyte activation (sCD163 and sCD14), and microbial translocation (lipopolysaccharide (LPS) and LPS binding protein) and liver fibrosis in patients with alcohol use disorder (AUD) and no overt liver disease is not well established. Methods: We studied patients admitted for treatment of AUD at two hospitals in Barcelona. Advanced liver fibrosis (ALF) was defined as FIB-4 > 3.25. Results: A total of 353 participants (76.3% male) were included and 94 (26.5%) had ALF. In adjusted correlation analyses, sCD163, sCD14, IL-6, IL-10, and LPS binding protein levels directly correlated with FIB-4 values (adjusted correlation coefficients 0.214, 0.452, 0.317, 0.204, and 0.171, respectively). However, LPS levels were inversely associated with FIB-4 (−0.283). All plasma marker levels in the highest quartile, except LPS, were associated with ALF (sCD163, sCD14, IL-6, IL-10, and LPS binding protein: adjusted odds ratio (aOR) 11.49 (95% confidence interval 6.42–20.56), 1.87 (1.11–3.16), 2.99 (1.79–5.01), 1.84 (1.11–3.16), and 2.13 (1.30–3.50), respectively). Conversely, LPS levels in the lowest quartile were associated with ALF (aOR 2.58 (1.48–4.58), p < 0.01). Conclusion: In AUD patients, plasma levels of the markers of inflammation, monocyte activation, and microbial translocation are associated with ALF.

Fungal plasma biomarkers in patients admitted for inpatient treatment of alcohol use disorder

“…Increased intestinal permeability and changes in the intestinal microbiome are important features of alcohol-related liver damage (Seitz et al, 2018). In previous studies, we demonstrated that increased levels of plasma markers of inflammation, monocyte activation, and microbial translocation are present in a sizable proportion of patients with AUD admitted for hospital detoxification; these increased levels were associated with advanced liver fibrosis (Fuster et al, 2021;García-Calvo et al, 2020). Fungi are commensals of the human intestine, and fungal dysbiosis appears to play a role in the development of alcohol-related liver damage but has received less attention in the literature than microbial dysbiosis (Yang et al, 2017).…”

“…The following day, blood was drawn to assess hematological and biochemical parameters and hepatitis C virus (HCV) infection. Additional information regarding the admission protocol and methods of HCV detection and sCD163, sCD14, Interleukin (IL)‐6, IL‐10, lipopolysaccharide (LPS), and LPS‐binding protein measurements were previously published (Fuster et al, 2021; García‐Calvo et al, 2020). The inter‐assay and intra‐assay coefficients of variation were <10% for all analyses.…”