Urinary 6β-hydroxycortisol excretion in Hong Kong Chinese patients with hepatocellular carcinoma and other chronic liver diseases

Abstract

BACKGROUND. The biotransformation of xenobiotics into toxic metabolites by cytochrome P-450 has been implicated in carcinogenesis. This study investigated CYP3A4 activity, which metabolically activates procarcinogens such as aflatoxin B1, by measuring the urinary 6β-hydroxycortisol (6βOHF) to free cortisol (F) ratio in patients with hepatocellular carcinoma (HCC) and other chronic liver diseases. METHODS. One hundred forty-three controls and 150 patients with different liver diseases, including chronic liver disease (due to alcoholism and/or chronic hepatitis B virus infection), cirrhosis (any cause), and resectable and nonresectable HCC, were recruited. Twenty-four hour urine samples were collected for measurement of 6βOHF and free cortisol by an enzyme-linked immunosorbent assay (ELISA) and a radioimmunoassay, respectively. RESULTS. Patients with nonresectable HCC showed a significant increase in 6βOHF excretion as well as their 6βOHF/F ratio (P < 0.05) when compared with the controls and other liver disease groups including patients with resectable HCC. The nonresectable HCC group showed a bimodal distribution in the 6βOHF/F ratio. Using a ratio of 9 or more in all HCC patients, the sensitivity and specificity of using the 6βOHF/F ratio to predict nonresectability of HCC was 48.8% and 92.6%, respectively. CONCLUSIONS. Our results show an increase in mean CYP3A4 enzyme activity, reflected as air increase in the 6βOHF/F ratio, in Hong Kong Chinese with nonresectable HCC compared with those with resectable HCC and other liver diseases. Although tire role of increased CYP3A4 activity in the aetiology of HCC is not known, our specificity and sensitivity estimates suggest that a high 6βOHF/F ratio indicates probable inoperability. However, a normal level is a poor predictor of resectability.