Impaired clearance of phenacetin in hepatic cirrhosis and fibrosis

OBJECTIVE: CYP450 1A2 is constitutively expressed in liver. Phenacetin O-de-ethylation is a marker reaction for CYP450 1A2 activity. In this paper, the metabolism of phenacetin has been studied in patients with chronic hepatitis B or cirrhosis secondary to a hepatitis B virus infection. The possibility of using the phenacetin test in the evaluation of liver function in these subjects has also been tested. SUBJECTS AND METHODS: Phenacetin pharmacokinetics and the recovery of its urinary metabolites were studied in 8 normal subjects, 16 patients with chronic hepatitis B and 12 patients with cirrhosis. The phenacetin test was performed in 18 normal subjects and 52 hepatocellular carcinoma (HCC) patients. The test was repeated in HCC patients after treatment with transcatheter arterial chemoembolization (TACE). RESULTS: Compared with normal controls, phenacetin apparent clearance decreased by 47.0% (p < 0.05) and 78.7% (p < 0.01) in patients with chronic hepatitis B and cirrhosis, respectively. The recovery of phenacetin O-de-ethylated metabolites decreased by 24.6 and 72.4% (p < 0.01). 46 of 52 HCC patients (88.4%) had an abnormal phenacetin test before TACE, where the ratio of plasma total acetaminophen to phenacetin was below the lower limit of the normal control range. The ratio was less than 50% of normal controls in 6 HCC patients who had a deterioration in liver function from Child-Pugh class A to Child-Pugh class B after TACE. CONCLUSION: The metabolism of phenacetin is impaired in patients with chronic hepatitis B and cirrhosis. The phenacetin test can predict the susceptibility of liver function to TACE in HCC patients.