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 6 beta-hydroxycortisol (6 beta OHF) 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 6 beta OHF and free cortisol by an enzyme-linked immunosorbent assay (ELISA) and a radioimmunoassay, respectively.
Results: Patients with nonresectable HCC showed a significant increase in 6 beta OHF excretion as well as their 6 beta OHF/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 6 beta OHF/F ratio. Using a ratio of 9 or more in all HCC patients, the sensitivity and specificity of using the 6 beta OHF/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 an increase in the 6 beta OHF/F ratio, in Hong Kong Chinese with nonresectable HCC compared with those with resectable HCC and other liver diseases. Although the role of increased CYP3A4 activity in the aetiology of HCC is not known, our specificity and sensitivity estimates suggest that a high 6 beta OHF/F ratio indicates probable inoperability. However, a normal level is a poor predictor of resectability.