非酒精性脂肪性肝病患儿肝法尼醇 X 受体蛋白水平与循环成纤维细胞生长因子 19 浓度。

Hepatic farnesoid X receptor protein level and circulating fibroblast growth factor 19 concentration in children with NAFLD.

机构信息

Hepato-metabolic Unit, Bambino Gesù Children's Hospital, Rome, Italy.

Liver Research Unit, Bambino Gesù Children's Hospital, Rome, Italy.

出版信息

Liver Int. 2018 Feb;38(2):342-349. doi: 10.1111/liv.13531. Epub 2017 Aug 18.

DOI:10.1111/liv.13531

PMID:28746779

Abstract

BACKGROUND & AIMS: Treatment with the farnesoid X receptor (FXR) agonist obeticholic acid is ineffective in some patients with non-alcoholic steatohepatitis (NASH) but the explanation is uncertain. We investigated hepatic FXR expression, and measurements of fibroblast growth factor 19 (FGF19) and bile acids (BAs) in children with NAFLD to investigate relationships with NASH.

METHODS

33 children with NAFLD who underwent diagnostic liver biopsy were studied. Hepatic FXR protein levels and circulating FGF19 concentrations were compared with those analysed in five control subjects with proven normal liver histology. NASH was defined by the Paediatric NAFLD Histological Score (PNHS). Binary logistic regression with adjustment for covariates and potential confounders was undertaken to test factors independently associated with: a) NASH and b) hepatic FXR protein levels.

RESULTS

Mean ± SD age was 13.7 ± 1.9 years. Nineteen patients had NASH (PNHS ≥ 85) and 14 did not have NASH (PNHS < 85). Hepatic FXR level and plasma FGF19 concentration varied ~10-fold and 5-fold, respectively, between groups, and was highest in control subjects, intermediate in NAFLD without NASH, and lowest in NASH (between group differences P < .001 and P < .01 respectively). NASH was independently associated with both FXR protein levels (OR = 0.18, 95% CI 0.09, 0.38) and FGF19 concentration (OR = 0.55, 95% CI 0.20, 0.89).

CONCLUSIONS

FXR protein levels vary markedly between normal liver, NAFLD without NASH, and NASH. Low levels of FXR are independently associated with NASH.

摘要

背景与目的

法尼醇 X 受体（FXR）激动剂奥贝胆酸治疗非酒精性脂肪性肝炎（NASH）在一些患者中无效，但原因尚不清楚。我们研究了儿童非酒精性脂肪性肝病（NAFLD）患者的肝 FXR 表达，并检测了成纤维细胞生长因子 19（FGF19）和胆汁酸（BAs）的水平，以探讨其与 NASH 的关系。

方法

对 33 例接受诊断性肝活检的 NAFLD 患儿进行了研究。比较了肝 FXR 蛋白水平和循环 FGF19 浓度与 5 例经证实具有正常肝组织学的对照者的分析结果。NASH 定义为小儿非酒精性脂肪性肝病组织学评分（PNHS）≥85。采用二元逻辑回归分析调整协变量和潜在混杂因素，以测试与：a）NASH 和 b）肝 FXR 蛋白水平独立相关的因素。

结果

平均年龄为 13.7±1.9 岁。19 例患者患有 NASH（PNHS≥85），14 例患者未患有 NASH（PNHS<85）。肝 FXR 水平和血浆 FGF19 浓度在各组之间变化约 10 倍和 5 倍，对照组最高，NAFLD 无 NASH 组次之，NASH 组最低（组间差异 P<0.001 和 P<0.01）。NASH 与 FXR 蛋白水平（OR=0.18，95%CI 0.09，0.38）和 FGF19 浓度（OR=0.55，95%CI 0.20，0.89）独立相关。