Are recommended doses of acetaminophen hepatotoxic for recently abstinent alcoholics?
Although acetaminophen overdose is a leading cause of fulminant hepatic failure, it is controversial whether therapeutic doses of acetaminophen can cause hepatotoxicity in alcoholics, especially those rendered most vulnerable by recent abstinence. We performed a randomized, triple-blind, parallel-group trial comparing sustained-release acetaminophen, 1300mg orally q8h for 11 doses, against placebo. We enrolled chronic alcohol abusers (defined as >= 6 drinks daily for >= 6 weeks) who had discontinued alcohol consumption 12 to 72 hours prior to enrolment. Individuals with self-reported viral hepatitis, HIV or intravenous drug use, baseline AST or ALT > 120 IU/L, or INR 1.5 were excluded. Hepatic function tests were drawn daily for 5 days. The primary outcome was change in serum alpha-GST, a sensitive experimental biomarker of hepatocellular injury; secondary outcomes were changes in serum AST, ALT, INR, and study withdrawal for a doubling of aminotransferases to > 120 IU/L. Of 52 subject
