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Aliment Pharmacol Ther. 2017 Jul;46(2):175-182. doi: 10.1111/apt.14119. Epub 2017 May 2.

Significant positive association of endotoxemia with histological severity in 237 patients with non-alcoholic fatty liver disease.

Author information

1
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.
2
State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong.
3
Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong.

Abstract

BACKGROUND:

Patients with nonalcoholic steatohepatitis (NASH) have gut dysbiosis and intestinal bacterial overgrowth.

AIM:

To test the hypothesis that endotoxemia is associated with the histological severity of nonalcoholic fatty liver disease (NAFLD) and determine factors associated with endotoxemia.

METHODS:

The endotoxemia markers lipopolysaccharide-binding protein (LBP) and endotoxin levels were measured in 237 NAFLD patients 1 day before liver biopsy. Biomarkers of liver injury and transient elastography were performed as additional markers of disease severity.

RESULTS:

A total of 114/237 (48%) patients had NASH and 80/237 (34%) had F2-4 fibrosis. LBP was correlated with lobular inflammation (P=.001), while both LBP (P=.0004) and endotoxin levels (P=0.008) were correlated with fibrosis. LBP was also correlated with cytokeratin-18 fragments (P=.002) and aspartate aminotransferase-to-alanine aminotransferase ratio (P=.006), and both LBP (P=.019) and endotoxin (P=.006) were correlated with liver stiffness measurement by transient elastography. LBP was increased in patients with NASH (15.3±4.6 vs 13.8±3.3 μg/mL; P=.005) and F2-4 fibrosis (15.4±4.4 vs 14.0±3.7 μg/mL; P=.008). Interestingly, patients harbouring the TM6SF2 rs58542926 T allele that predispose to NAFLD/NASH had higher LBP level. By multivariate analysis, gender, higher body mass index and glycated haemoglobin, and TM6SF2 variants were independent factors associated with increased LBP level.

CONCLUSIONS:

Endotoxemia is positively associated with NASH and significant fibrosis. The association between TM6SF2 and endotoxemia warrants further investigations. The findings may shed light on the pathogenesis of NASH and inform a novel treatment target.

PMID:
28464257
DOI:
10.1111/apt.14119
[Indexed for MEDLINE]
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