Study of the Urinary Ratio of 6 ß-Hydroxycortisol/Cortisol as a Biomarker of CYP3A4 Activity in Egyptian Patients with Chronic Liver Diseases

Abstract

Summary: The urinary ratio of 6 ß-hydroxycortisol/cortisol (6 ß-OHC/C) as a biomarker of CYP3A4 metabolizing activity has been studied in Egyptian patients with chronic liver cirrhosis associated with previous hepatic Schistosomiasis infection to determine any possible alteration in enzyme activity. The ratio of 6-ß OHC/C was determined in morning urine samples collected from 8:00 a.m. to 12:00 p.m. in healthy adults (n = 36) and patients with liver cirrhosis (n = 57). The median age for control was 27 years (range: 18-50 years) and 50 years (range: 27-75 years) for patients. 6 ß-OHC was detected in urine by ELIZA kits (Stabiligen, France). Patients with liver cirrhosis were categorized according to Child Pugh Classifi cation into Child B (n = 28) and Child C (n = 29) classes. Cholestasis was observed in 9/28 of Child B class and 8/29 of Child C class of patients. The control subjects showed gender-related difference in the urinary ratio of 6 ß-OHC/C. A significant reduction (P < 0.001) in 6 ß-OHC/C ratio was observed only in Child C patients in comparison with control subjects. Regression analysis showed a signifi cant correlation (P < 0.05) between 6 ß-OHC/C ratio and serum albumin. The infl uence of cholestasis on the urinary ratio of 6-ß OHC/C was observed on cirrhotic patients of Child B class. In conclusion, patients with chronic liver cirrhosis might have a reduction of metabolizing activity of CYP3A4 enzymes which could be identifi ed by measuring the urinary ratio of 6 ß-OHC/C. This reduction is more apparent in severe liver injury (Child C class). Therefore, it is important to understand the metabolic fate of drugs metabolized by 3A4 enzymes in patients with liver cirrhosis to avoid drug accumulation that might lead to development of drug toxicity.

Keywords

• 6 ß-hydroxycortisol/cortisol ratio
• CYP 3A4
• hepatic cirrhosis