Targher Giovanni, Bertolini Lorenzo, Rodella Stefano, Zoppini Giacomo, Zenari Luciano, Falezza Giancarlo
Division of Internal Medicine, Sacro Cuore Hospital, Negrar, VR, Italy.
Clin Endocrinol (Oxf). 2006 Mar;64(3):337-41. doi: 10.1111/j.1365-2265.2006.02466.x.
To assess associations between the activity of hypothalamo-pituitary-adrenal (HPA) axis and liver histology in patients with nonalcoholic fatty liver disease (NAFLD).
In a cross-sectional study, we enrolled 50 consecutive, overweight, NAFLD patients and 40 control subjects who were comparable for age, sex and body mass index (BMI).
NAFLD (by liver biopsy), HPA axis activity (by 24-hour urinary free cortisol [UFC] excretion and serum cortisol levels after 1 mg dexamethasone), insulin resistance (by homeostasis model assessment: HOMA-IR), and metabolic syndrome (MetS) features.
NAFLD patients had markedly higher (P < 0.001) 24-h UFC (149 +/- 24 vs. 90 +/- 16 nmol/day) and postdex suppression cortisol concentrations (32 +/- 10 vs. 16 +/- 7 nmol/l) than controls. The MetS and its individual components were more frequent among NAFLD patients. The marked differences in urinary/serum cortisol concentrations that were observed between the groups were little affected by adjustment for age, sex, BMI, waist circumference, systolic blood pressure, triglycerides, homeostasis model assessment for insulin resistance score and presence of diabetes. Importantly, 24-h UFC and postdex cortisol concentrations strongly correlated to hepatic necroinflammatory grade (P < 0.01) and fibrosis stage (P < 0.001) among NAFLD patients. By logistic regression analysis, 24-h UFC (odds ratio (OR) 1.80, 95%CI 1.3-2.8) or postdex cortisol concentrations (OR 1.95, 95%CI 1.4-3.1) independently predicted the severity of hepatic fibrosis, but not necroinflammation, after adjustment for potential confounders.
These results suggest that NAFLD patients have a subtle, chronic overactivity in the HPA axis (that is closely associated with the severity of liver histopathology) leading to subclinical hypercortisolism that might be implicated in the development of NAFLD.
评估非酒精性脂肪性肝病（NAFLD）患者下丘脑-垂体-肾上腺（HPA）轴活性与肝脏组织学之间的关联。
在一项横断面研究中，我们连续纳入了50例超重的NAFLD患者和40名年龄、性别及体重指数（BMI）相匹配的对照受试者。
NAFLD（通过肝活检）、HPA轴活性（通过24小时尿游离皮质醇[UFC]排泄量及1毫克地塞米松后的血清皮质醇水平）、胰岛素抵抗（通过稳态模型评估：HOMA-IR）以及代谢综合征（MetS）特征。
NAFLD患者的24小时UFC（149±24 vs. 90±16 nmol/天）和地塞米松抑制后皮质醇浓度（32±10 vs. 16±7 nmol/L）显著高于对照组（P<0.001）。MetS及其各个组分在NAFLD患者中更为常见。在对年龄、性别、BMI、腰围、收缩压、甘油三酯、胰岛素抵抗稳态模型评估得分及糖尿病存在情况进行校正后，两组间观察到的尿/血清皮质醇浓度的显著差异几乎未受影响。重要的是，在NAFLD患者中，24小时UFC和地塞米松抑制后皮质醇浓度与肝脏坏死性炎症分级（P<0.01）和纤维化阶段（P<0.001）密切相关。通过逻辑回归分析，在对潜在混杂因素进行校正后，24小时UFC（比值比[OR] 1.80，95%可信区间[CI] 1.3 - 2.8）或地塞米松抑制后皮质醇浓度（OR 1.95，95%CI 1.4 - 3.1）可独立预测肝纤维化的严重程度，但不能预测坏死性炎症的严重程度。
这些结果表明，NAFLD患者的HPA轴存在轻微的慢性过度活跃（这与肝脏组织病理学的严重程度密切相关），导致亚临床高皮质醇血症，这可能与NAFLD的发生有关。
