CHANGES IN TRANSAMINASES OVER THE COURSE OF A 12-WEEK, DOUBLE-BLIND NALMEFENE TRIAL IN A 38-YEAR-OLD FEMALE SUBJECT

A 38-year-old female was drinking 30 drinks/week before entering a 12- week, double-blind study of nalmefene for the treatment of alcohol dep endence. Liver function tests (LFTs) were within normal limits at base line and week 4, but on week 8, the ALT showed a 7-fold increase, and the AST showed a 4-fold increase from baseline. A decision was made to continue study medication based on the patient's positive response to this therapy (i.e., achieving complete abstinence) and no known dose- dependent association with liver toxicity in over 1300 patients treate d with nalmefene for other indications. LFTs were repeated serially to assess the trend of the LFT values. The patient achieved total abstin ence over the course of the study period and at the 3-month posttreatm ent follow-up was continuing to maintain these gains from the study pr ogram, and her LFTs had returned to normal. A gradual return to normal in ALT and ART, while treatment with nalmefene continued, does not su pport the role of nalmefene as an hepatotoxin. Relapse to drinking was excluded because of normal values for the gamma-glutamyltransferase, and verification of sobriety by self report, significant other, and br eathalyzer. A virology panel ruled out the presence of viral hepatitis . Dietary intake before the elevation in LFTs contained elements that have established association with hepatocellular changes. The routine prescription of serial LFTs in alcoholism pharmacotherapy trials may b e expected to reveal clinically nonsignificant elevations that could p otentially be related to exogenous factors, such as dietary compositio n and should not be reflexively attributed to medication under investi gation and/or drinking.