Journal Article

Pro-Inflammatory Cytokines but Not Endotoxin-Related Parameters Associate with Disease Severity in Patients with NAFLD

Vander Elst, Ingrid, Hubens, Guy, du Plessis, Johannie, Windmolders, Petra, Van Gaal, Luc, Nevens, Frederik, Cassiman, David, Francque, Sven, Korf, Hannelie, Verrijken, An, van der Merwe, Schalk, van Pelt, Jos

2016

Overview

Intestinal dysbiosis and elevated lipopolysaccharides (LPS) levels have been implicated in the development of obesity, insulin resistance and non-alcoholic steatohepatitis (NASH). In order to determine if LPS levels are elevated in patients with NASH compared to patients with non-alcoholic fatty liver (NAFL) and, if elevated LPS levels correlated with histological severity of non-alcoholic fatty liver disease (NAFLD) we compared LPS, markers of LPS bioactivity and pro-inflammatory cytokines/chemokines in patients undergoing bariatric surgery. At the time of surgery a liver biopsy was taken allowing the stratification into well-delineated subgroups including: No NAFL/NAFL; NASH; NASH with fibrosis and NASH cirrhotics, using the NAFLD Activity Score (NAS). Anthropometric data and plasma were collected for assessment of LPS, lipopolysaccharide binding protein (LBP), soluble CD14 (sCD14), intestinal-type fatty acid binding protein (iFABP), Toll-like receptors 2 and 4 (TLR2, 4) and a panel of cytokines/chemokines. Similar analysis was performed on plasma from a cohort of healthy controls. Our data indicate elevated levels of LPS, LBP, sCD14, iFABP and TLR2,4 in obese patients compared to healthy controls, however, these parameters remained unaltered within patients with limited liver disease (NAFL) compared to NASH/NASH with fibrosis subgroups. Hierarchic cluster analysis using endotoxin-related parameters failed to discriminate between lean controls, NAFLD. While similar cluster analysis implementing inflammation-related parameters clearly distinguished lean controls, NALFD subgroups and NASH cirrhotics. In addition, LPS levels was not associated with disease severity while TNFα, IL8, and CCL3 featured a clear correlation with transaminase levels and the histological severity of NALFD. In conclusion our data indicate a stronger correlation for circulating inflammatory- rather than endotoxin-related parameters in progression of NAFLD and highlights the need for additional larger studies in unravelling further mechanistic insights.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acute-Phase Proteins / Adult / Anthropometry / Bariatric Surgery / Biological activity / Biology and Life Sciences / Biopsy / Care and treatment / Carrier Proteins - blood / CCL3 protein / CD14 antigen / Chemokines / Chemokines - blood / Cluster Analysis / Clusters / Correlation / Cytokines / Cytokines - blood / Development and progression / Disease control / Dysbacteriosis / Endotoxins / Endotoxins - metabolism / Fatty acid-binding protein / Fatty acids / Fatty liver / Female / Fibrosis / Gastroenterology / Gastrointestinal surgery / Gene expression / Genetic aspects / Health aspects / Hepatology / Histology / Humans / Immune response / Immune system / Inflammation / Insulin / Insulin resistance / Interleukin 8 / Internal medicine / Intestine / Laboratories / Lipopolysaccharides / Lipopolysaccharides - blood / Liver / Liver cirrhosis / Liver diseases / Male / Medicine / Medicine and Health Sciences / Membrane Glycoproteins - blood / Metabolism / Microbiota / Middle Aged / Mitochondrial DNA / Non-alcoholic Fatty Liver Disease - immunology / Non-alcoholic Fatty Liver Disease - metabolism / Non-alcoholic Fatty Liver Disease - pathology / Obesity / Obesity - immunology / Obesity - metabolism / Obesity - surgery / Pathogenesis / Patients / Permeability / Prospective Studies / Proteins / Receptors / Rodents / Studies / Subgroups / Surgery / TLR2 protein / Toll-like receptors / Transaminase / Tumor necrosis factor-TNF / Tumor necrosis factor-α