Objectives: To assess associations between the activity of hypothalamo-pituitary-adrenal (HPA) axis and liver histology in patients with nonalcoholic fatty liver disease (NAFLD).
Design and patients: 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).
Measurements: 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.
Results: 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.
Conclusions: 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.