TY - JOUR
T1 - Novel evidence for chronic exposure to endotoxin in human nonalcoholic steatohepatitis.
AU - Verdam, F.J.
AU - Rensen, S.S.M.
AU - Driessen, A.L.C.
AU - Greve, J.W.M.
AU - Buurman, W.A.
PY - 2011/1/1
Y1 - 2011/1/1
N2 - 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. GOALS: 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. STUDY: 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.
AB - 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. GOALS: 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. STUDY: 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.
U2 - 10.1097/MCG.0b013e3181e12c24
DO - 10.1097/MCG.0b013e3181e12c24
M3 - Article
SN - 0192-0790
VL - 45
SP - 149
EP - 152
JO - Journal of Clinical Gastroenterology
JF - Journal of Clinical Gastroenterology
IS - 2
ER -