URINARY 6-BETA-HYDROXYCORTISOL EXCRETION IN HONG-KONG CHINESE PATIENTS WITH HEPATOCELLULAR-CARCINOMA AND OTHER CHRONIC LIVER-DISEASES

BACKGROUND. The biotransformation of xenobiotics into toxic metabolite s by cytochrome P-450 has been implicated in carcinogenesis. This stud y investigated CYP3A4 activity, which metabolically activates procarci nogens such as eflatoxin B-1, by measuring the urinary 6 beta-hydroxyc ortisol (6 beta OHF) to free cortisol (F) ratio in patients with hepat ocellular carcinoma (HCC) and other chronic liver diseases. METHODS, O ne hundred forty-three controls and 150 patients with different liver diseases, including chronic liver disease (due to alcoholism and/or ch ronic hepatitis B virus infection), cirrhosis (any cause), and resecta ble and nonresectable HCC, were recruited. Twenty-four hour urine samp les were collected for measurement of 6 beta OHF and free cortisol by an enzyme-linked immunosorbent assay (ELISA) and a radioimmunoassay, r espectively. RESULTS, Patients with nonresectable HCC showed a signifi cant increase in 6 beta OHF excretion as well as their 6 beta OHF/F ra tio (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 6beta>OHF/F ratio. Using a ratio of 9 or more in all HCC patients, the sensitivity and specificit y of using the 6 beta OHF/F ratio to predict nonresectability of HCC w as 48.8% and 92.6%, respectively. CONCLUSIONS, Our results show an inc rease in mean CYP3A4 enzyme activity, reflected as an increase in the 6 beta OHF/F ratio, in Hong Kong Chinese with nonresectable HCC compar ed with those with resectable HCC and other liver diseases. Although t he role of increased CYP3A4 activity in the aetiology of HCC is not kn own, our specificity and sensitivity estimates suggest that a high 6 b eta OHF/F ratio indicates probable inoperability. However, a normal le vel is a poor predictor of resectability. (C) 1996 American Cancer Soc iety.