Novel evidence for chronic exposure to endotoxin in human nonalcoholic steatohepatitis.
BACKGROUND
Endotoxin is hypothesized to play an important role in the activation of inflammatory pathways associated with nonalcoholic steatohepatitis (NASH). However, demonstration of hepatic endotoxin exposure is challenging due to the inaccessibility of the portal circulation. Furthermore, reliable measurement of the relatively low endotoxin levels in plasma of patients with liver disease and subsequent interpretation remain difficult.


OBJECTIVE
In this study, we used the EndoCab assay that measures endogenous antibodies to the core region of endotoxin to estimate hepatic endotoxin exposure over time.


METHODS
IgG levels against endotoxin were measured in peripheral plasma obtained from 21 severely obese patients with NASH and 9 severely obese patients with healthy livers.


RESULTS
Plasma IgG levels against endotoxin were significantly elevated in patients with NASH compared with patients with healthy livers (48±63 GMU/mL vs. 10±13 GMU/mL). Moreover, these IgG levels progressively increased with NASH grade (grade 1 29±37; grade 2 58±51; grade 3 84±132 GMU/mL, P<0.05). There was no relation between plasma IgG levels and NASH stage.


CONCLUSIONS
Plasma IgG levels against endotoxin were found to be increased in biopsy-proven human NASH and increased with aggravated inflammation in NASH, suggesting a relationship between chronic endotoxin exposure and the severity of human NASH.
Verdam
Froukje J
FJ
Department of General Surgery, Faculty of Health, Medicine and Life Sciences, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht, The Netherlands.
Rensen
Sander S
SS
Driessen
Ann
A
Greve
Jan Willem
JW
Buurman
Willem A
WA
D000328:Adult; D000906:Antibodies / Q000097:blood*; D004731:Endotoxins / Q000097:blood / Q000276:immunology*; D005234:Fatty Liver / Q000150:complications / Q000209:etiology* / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000150:complications
D000906:Antibodies; D004731:Endotoxins; D007074:Immunoglobulin G