TY - JOUR
T1 - Endotoxin and plasminogen activator inhibitor-1 serum levels associated with nonalcoholic steatohepatitis in children
AU - Alisi, Anna
AU - Manco, Melania
AU - Devito, Rita
AU - Piemonte, Fiorella
AU - Nobili, Valerio
PY - 2010/6
Y1 - 2010/6
N2 - OBJECTIVES: Recent evidence supports a role for endotoxemia in the progression from nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH). We investigated the association between serum levels of endotoxin, proinflammatory molecules, and histology in children with NAFLD. PATIENTS AND METHODS: A total of 40 children, mean age of 11.9 ± 2.8 years (27 male and 13 female), with biopsy-proven NAFLD were consecutively enrolled. Anthropometrics, blood pressure, and parameters of the metabolic syndrome were collected. Serum levels of endotoxin, plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were measured by an enzyme-linked immunosorbent assay and compared with circulating levels of the same soluble factors in 9 age- and sex-matched normal weight controls (age 11.4 ± 1.7 years; 6 boys and 3 girls). RESULTS: Children with NAFLD had markedly higher serum concentrations of endotoxin (P <0.01), PAI-1 (P <0.001), TNF-α, and IL-6 (P <0.05) than control subjects. Endotoxin (P = 0.002), PAI-1, (P <0.001), IL-6 (P = 0.002), TNF-α (P = 0.02), and body mass index (P = 0.03) were significantly associated with a NAFLD activity score ≥5 at the univariate analysis. At the stepwise regression analysis, endotoxin (P <0.0001) and PAI-1 (P = 0.009) were the most significant predictors for NAFLD activity score. CONCLUSIONS: Our findings demonstrate that, apart from TNF-α and IL-6, endotoxin and PAI-1 may represent good markers of NASH. They also reinforce the hypothesis that elevated levels of endotoxin may contribute to the progression from NAFLD to NASH.
AB - OBJECTIVES: Recent evidence supports a role for endotoxemia in the progression from nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH). We investigated the association between serum levels of endotoxin, proinflammatory molecules, and histology in children with NAFLD. PATIENTS AND METHODS: A total of 40 children, mean age of 11.9 ± 2.8 years (27 male and 13 female), with biopsy-proven NAFLD were consecutively enrolled. Anthropometrics, blood pressure, and parameters of the metabolic syndrome were collected. Serum levels of endotoxin, plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were measured by an enzyme-linked immunosorbent assay and compared with circulating levels of the same soluble factors in 9 age- and sex-matched normal weight controls (age 11.4 ± 1.7 years; 6 boys and 3 girls). RESULTS: Children with NAFLD had markedly higher serum concentrations of endotoxin (P <0.01), PAI-1 (P <0.001), TNF-α, and IL-6 (P <0.05) than control subjects. Endotoxin (P = 0.002), PAI-1, (P <0.001), IL-6 (P = 0.002), TNF-α (P = 0.02), and body mass index (P = 0.03) were significantly associated with a NAFLD activity score ≥5 at the univariate analysis. At the stepwise regression analysis, endotoxin (P <0.0001) and PAI-1 (P = 0.009) were the most significant predictors for NAFLD activity score. CONCLUSIONS: Our findings demonstrate that, apart from TNF-α and IL-6, endotoxin and PAI-1 may represent good markers of NASH. They also reinforce the hypothesis that elevated levels of endotoxin may contribute to the progression from NAFLD to NASH.
KW - Endotoxin
KW - Inflammation
KW - NAFLD
KW - NASH
KW - PAI-1
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U2 - 10.1097/MPG.0b013e3181c7bdf1
DO - 10.1097/MPG.0b013e3181c7bdf1
M3 - Article
C2 - 20400911
AN - SCOPUS:77953161601
VL - 50
SP - 645
EP - 649
JO - Journal of Pediatric Gastroenterology and Nutrition
JF - Journal of Pediatric Gastroenterology and Nutrition
SN - 0277-2116
IS - 6
ER -