Reduced urinary 6beta-hydroxycortisol to cortisol ratios in patients with liver cirrhosis.
While the urinary concentration ratio of 6beta-hydroxycortisol (6beta-HC) to cortisol (C) in 24-h urine samples is an established parameter for the induction of hepatic cytochrome P450 (CYP) 3A activity, it remains unclear whether it would be reduced in association with chronic liver damages. To clarify this issue we measured this parameter in 12 patients with chronic hepatitis, 15 patients with liver cirrhosis and 12 healthy subjects. Urinary 6beta-HC and C were assayed with high-performance liquid chromatography with ultraviolet absorption. Multiple regression analysis was performed to search for which biochemical or demographic parameter(s) would be associated with the overall variability of urinary 6beta-HC/C ratios. Results showed that the mean (+/-S.D.) 6beta-HC/C ratio obtained from the patients with liver cirrhosis (4.3+/-2.6), but not that from patients with chronic hepatitis (7.4+/-7.2), was significantly (P<0.05) lower than that obtained from the healthy controls (11.8+/-8.3). It was also revealed that among the clinical parameters examined (e.g. serum transaminases concentrations) only serum albumin concentrations were correlated significantly (R=0.61, P<0.05) with the urinary 6beta-HC/C ratio. In conclusion, the present study implies that that the reduced urinary 6beta-HC/C ratios in patients with liver cirrhosis may be associated with attenuated hepatic CYP3A activity in these patients.
Shibuya
Masahiko
M
Department of Hospital Pharmacy, National Hospital Tokyo Medical Center, Tokyo, Japan
Echizen
Hirotoshi
H
Kubo
Suzuko
S
Tamura
Noboru
N
Suzuki
Koichi
K
Ushiama
Hideki
H
Ohnishi
Akihiro
A