Table 1.
Baseline clinical characteristics of patients with hepatic steatosis, NASH and controls.
Figure 1.
24 hour urine steroid metabolite analysis from patients with steatosis and steatohepatitis compared with obese controls.
(A): 5α-reductase activity as depicted by the urinary 5αTHF/THF ratio (mean ± SEM). (B): total 24 Urine 5α-reduced metabolites (mean ± SEM) (Andros: androsterone). (C): total 24 hr Urine F metabolites (mean ± SEM).
Table 2.
Urinary steroid metabolites and ratios in patients with steatosis, NASH and control patients.
Figure 2.
11β-HSD1 activity assessed by:
(A) 24 hr urine cortols/cortolones and 5αTHF+THF/THE ratios (mean ± SEM) in patients with steatosis and steatohepatitis compared with controls. (B) Hepatic cortisol generation measured by cortisol generation profiles (mean AUC ± SEM) in patients with steatosis and steatohepatitis compared with controls.
Figure 3.
Real time PCR mRNA expression data on whole liver samples from 5 normal patients and 5 NASH patients (expressed as arbitrary units ± SEM) for (A)HSD11B1 (11β-HSD 1), (B)SRD5A2 (5α-reductase 2), (C)GRα.
** p<0.01 NASH vs controls; * p<0.05 NASH vs controls.
Figure 4.
Hepatic 11β-HSD 1 immunoreactivity in patients with severe NASH compared to normal controls.
There was generally increased staining for 11β-HSD1 throughout the liver parenchyma in (A) NASH samples compared with (B) Normal liver ×20. (C) and (D) Increased staining at the limiting plate in peri-septal areas and strongly staining specific cells within the inflammatory infiltrate in NASH ×10(C) and ×20(D) (E) Confocal microscopy on severe NASH cryosections. Green - 11β-HSD1, red – CD68 IgG macrophage marker, yellow – colocalisation of 11β-HSD1 and CD68 positive macrophages. (F) Western blot analysis of human liver microsomes from normal and NASH livers.
Figure 5.
Schematic: Hepatic glucocorticoid metabolism and its modulation in response to disease progression in NAFLD.