Significant positive association of endotoxemia with histological severity in 237 patients with non-alcoholic fatty liver disease.
Aliment Pharmacol Ther
; 46(2): 175-182, 2017 07.
Article
em En
| MEDLINE
| ID: mdl-28464257
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Endotoxemia
/
Hepatopatia Gordurosa não Alcoólica
Tipo de estudo:
Risk_factors_studies
Limite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Aliment Pharmacol Ther
Ano de publicação:
2017
Tipo de documento:
Article