The effect of transcatheter arterial chemoembolization on phase II drug metabolism enzymes in patients with hepatocellular carcinoma

Abstract

Transcatheter arterial chemoembolization (TACE) causes damage to liver function and decreases the activity of cytochrome P450 in patients with hepatocellular carcinoma (HCC). But there was no report on whether the activity of Phase II conjugating enzymes was affected in HCC patients after TACE treatment. The purpose of the study was to assess the effect of TACE on the activity of UDP-glucuronosyltransferases (UGTs) and sulfotransferases (SULTs) in HCC patients. The acetaminophen test was performed on 12 normal subjects and 26 HCC patients. The contents of acetaminophen and its metabolites in blood and urine were determined by HPLC method. The recoveries of acetaminophen glucuronide (AG) and acetaminophen sulfate (AS) in plasma and urine were investigated. Compared with pre-TACE treatment, serum albumin decreased by 10.3%, bilirubin increased by 50.9%, prothrombin time was prolonged by 10.4%, serum alanine aminotransferase increased by 1.27-fold and aspartate aminotransferase increased by 1.29-fold in HCC patients after TACE (p < 0.01). But there was no significant difference on the contents of blood and urinary free and conjugated acetaminophen in HCC patients before and after TACE. Compared with normal controls, the ratio of urinary AG to AS was just 13.2% (p < 0.01) in HCC patients. TACE possesses apparent damage to liver function, but it does not affect the activity of UGTs and SULTs in HCC patients. The metabolism pathway of acetaminophen was altered for HCC patients: acetaminophen was metabolized mainly into AS for HCC patients but mainly into AG for healthy volunteers.