Harte, A. L., da Silva, Nancy F., Creely, Steven J., McGee, K. C., Billyard, Thomas, Youssef-Elabd, Elham M., Tripathi, Gyanendra, Ashour, Esmat, Abdalla, Mohga S., Sharada, Hayat M., Amin, Ashraf I., Burt, Alastair D., Kumar, Sudhesh, Day, Christopher Paul and McTernan, P. G. (2010) Elevated endotoxin levels in non-alcoholic fatty liver disease. Journal of Inflammation, Vol.7 . Article 15. doi:10.1186/1476-9255-7-15

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Abstract

Background: Emerging data indicate that gut-derived endotoxin may contribute to low-grade systemic inflammation
in insulin resistant states. This study aimed to examine the importance of serum endotoxin and inflammatory markers
in non-alcoholic fatty liver disease (NAFLD) patients, with and without type 2 diabetes mellitus (T2DM), and to explore
the effect of treatment with a lipase inhibitor, Orlistat, on their inflammatory status.
Methods: Fasted serum from 155 patients with biopsy proven NAFLD and 23 control subjects were analysed for
endotoxin, soluble CD14 (sCD14), soluble tumour necrosis factor receptor II (sTNFRII) and various metabolic
parameters. A subgroup of NAFLD patients were re-assessed 6 and 12 months after treatment with diet alone (n = 6) or
diet plus Orlistat (n = 8).
Results: Endotoxin levels were significantly higher in patients with NAFLD compared with controls (NAFLD: 10.6(7.8,
14.8) EU/mL; controls: 3.9(3.2, 5.2) EU/mL, p < 0.001); NAFLD alone produced comparable endotoxin levels to T2DM
(NAFLD: T2DM: 10.6(5.6, 14.2) EU/mL; non-diabetic: 10.6(8.5, 15.2) EU/mL), whilst a significant correlation between
insulin resistance and serum endotoxin was observed (r = 0.27, p = 0.008). Both sCD14 (p < 0.01) and sTNFRII (p < 0.001)
increased with severity of fibrosis. A positive correlation was also noted between sTNFRII and sCD14 in the NAFLD
subjects (r = 0.29, p = 0.004).
Sub-cohort treatment with Orlistat in patients with NAFLD showed significant decreases in ALT (p = 0.006), weight (p
= 0.005) and endotoxin (p = 0.004) compared with the NAFLD, non-Orlistat treated control cohort at 6 and 12 months
post therapy, respectively.
Conclusions: Endotoxin levels were considerably increased in NAFLD patients, with marked increases noted in early
stage fibrosis compared with controls. These results suggest elevated endotoxin may serve as an early indicator of
potential liver damage, perhaps negating the need for invasive liver biopsy. As endotoxin may promote insulin
resistance and inflammation, interventions aimed at reducing endotoxin levels in NAFLD patients may prove beneficial
in reducing inflammatory burden.

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine
Divisions:	Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Fatty liver, Endotoxins, Lipase -- Inhibitors
Journal or Publication Title:	Journal of Inflammation
Publisher:	BioMed Central Ltd.
ISSN:	1476-9255
Official Date:	2010
Dates:	Date Event 2010 Published
Volume:	Vol.7
Page Range:	Article 15
DOI:	10.1186/1476-9255-7-15
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
Funder:	Lilly Research Laboratories, British Heart Foundation

Data sourced from Thomson Reuters' Web of Knowledge

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