Blood endotoxins may aid disease detection, staging in NAFLD
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Blood endotoxin levels were increased among patients with nonalcoholic fatty liver disease compared with healthy controls and may serve as a relevant diagnostic biomarker, according to research in Clinical Gastroenterology and Hepatology.
“NAFLD is asymptomatic during early development, thus hindering early disease detection. Moreover, even during progression of the disease, noninvasive diagnostic tools for a reliable diagnosis and disease staging are lacking,” Josefin Soppert, MS, a PhD candidate at the Institute for Molecular Cardiovascular Research at University Hospital RWTH Aachen in Germany, and colleagues wrote. “Increasing evidence suggests the importance of gut-derived microbial constituents in NAFLD progression. ... Previous studies have reported increased levels of endotoxins in blood and liver of patients with biopsy-proven NAFLD. However, a high variability of the reported blood endotoxin concentrations is noted among studies.”
“NAFLD is asymptomatic during early development, thus hindering early disease detection. Moreover, even during progression of the disease, noninvasive diagnostic tools for a reliable diagnosis and disease staging are lacking,” Josefin Soppert, MS, and colleagues wrote. Source: Adobe Stock
In a systematic review and meta-analysis, Soppert and colleagues evaluated 43 studies to determine endotoxin values and potential relationships to disease stage, age, sex, parameters of systemic inflammation, metabolic syndrome, liver function and histology.
They reported higher blood endotoxin levels among patients with simple steatohepatitis compared with healthy controls (standardized mean difference [SMD] = 0.86; 95% CI, 0.62-1.11) as well as among patients with nonalcoholic steatohepatitis compared with nonalcoholic fatty liver and non-NASH patients (SMD = 0.81; 95% CI, 0.27-1.35). Further, patients with more advanced histopathological gradings of liver steatosis and fibrosis had “consistently higher” endotoxin levels.
A rise in BMI among patients with NAFLD also correlated with increased blood endotoxin levels ( = 0.2217; 95% CI, 0.0391-0.4043), and meta-analysis revealed a “significant increase” in biochemical parameters of systemic inflammation (C-reactive protein), metabolic syndrome and liver dysfunction.
“Our meta-analysis revealed that blood endotoxin levels are increased in NAFLD patients compared to liver-healthy controls, also after compensation for differences in BMI,” Soppert and colleagues concluded. “Increased blood endotoxin levels were already detected in simple steatosis patients vs. liver-healthy controls as well as in NASH vs. NAFL/non-NASH patients, overall suggesting blood endotoxin levels as potential biomarker for NAFLD.
“For a future clinical application of blood endotoxins as noninvasive diagnostic tool, additional clinical trials addressing the diagnostic accuracy of systemic endotoxin levels, alone or in combination with other parameters, as noninvasive biomarker for NAFLD onset and progression as well as intestinal permeability are required.”
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