Blood endotoxin levels as biomarker of non-alcoholic fatty liver disease: a systematic review and meta-analysis
Josefin Soppert et al.
Background and Aims: Growing evidence supports a role of gut-derived metabolitesin non-alcoholic fatty liver disease (NAFLD), but the relation of endotoxin levels with gut permeability and NAFLD stage remains unclear. This systematic review with meta- analysis aims to provide further insights.
Methods: PubMed, Embase and Cochrane Library were searched for studies published until January 2022 assessing blood endotoxins in patients with NAFLD. Meta-analyses, univariate/multivariate meta-regression as well as correlation analyses were performed for endotoxin values and potential relationships to disease stage, age, sex, parameters of systemic inflammation, metabolic syndrome as well as liver function and histology. Results: 43 studies were included, of which 34 for meta-analyses. Blood endotoxin levels were higher in simple steatosis patients vs. liver-healthy controls (SMD=0.86, CI=0.62-1.11) as well as in NASH vs. NAFL/non-NASH patients (SMD=0.81, CI=0.27- 1.35, P=.0078). Consistently, higher endotoxin levels were observed in patients with more advanced histopathological gradings of liver steatosis and fibrosis. An increase of blood endotoxin levels was partially attributed to a BMI-rise in NAFLD patients compared to controls. Nevertheless, significant increases of blood endotoxin levels in NAFLD retained after compensation for differences in BMI, metabolic condition or liver enzymes. Increases in blood endotoxin levels were associated with increases in CRP concentrations and in most cases paralleled a rise in markers for intestinal permeability. Conclusion: Our results support blood endotoxin levels as relevant diagnostic biomarker for NAFLD, both for disease detection as well as staging during disease progression, and might serve as surrogate marker of enhanced intestinal permeability in NAFLD.