title: Acute liver and renal failure during treatment with buprenorphine at therapeutic dose.
abstract: Buprenorphine is a semi-synthetic opioid derivative commonly used in the treatment of heroin addiction. Life-threatening complications have been described following overdoses while few cases of hepatotoxicity due to drug use at therapeutic doses have been recently described in hepatitis C virus carriers. In these cases, however, histological assessment was not exhaustive and no extra-hepatic organ failure was observed. We describe herein a case of acute liver and kidney failure in a patient with previously latent hepatitis C virus chronic infection following recommended doses of buprenorphine. Histology did not demonstrate any feature compatible with hepatitis C virus reactivation or liver cirrhosis and suspension of the treatment led to the resolution of both liver and kidney failure. Causality criteria fulfillment indicates a high probability of buprenorphine-induced liver toxicity. No signs of pre-existant kidney impairment or of pre- or post-renal causes were observed. Since buprenorphine is metabolized through cytochrome P450 3A4, we genotyped six genetic polymorphisms previously described in poor metabolizers but could not confirm these pharmacogenetic bases in this case. In conclusion, we surmise that buprenorphine at suggested doses can induce liver and kidney failure in susceptible individuals, possibly through direct mitochondrial toxicity.
authors.affiliation: Department of Medicine, Division of Internal Medicine, San Paolo School of Medicine, University of Milan, Milan, Italy. massimo.zuin@unimi.it
authors.forename: M
authors.initials: M
authors.lastname: Zuin
authors.forename: A
authors.initials: A
authors.lastname: Giorgini
authors.forename: C
authors.initials: C
authors.lastname: Selmi
authors.forename: P M
authors.initials: PM
authors.lastname: Battezzati
authors.forename: C A
authors.initials: CA
authors.lastname: Cocchi
authors.forename: A
authors.initials: A
authors.lastname: Crosignani
authors.forename: A
authors.initials: A
authors.lastname: Benetti
authors.forename: P
authors.initials: P
authors.lastname: Invernizzi
authors.forename: M
authors.initials: M
authors.lastname: Podda
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced*; D000328:Adult; D002047:Buprenorphine / Q000009:adverse effects*; D006556:Heroin Dependence / Q000534:rehabilitation*; D006801:Humans; D017114:Liver Failure, Acute / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D009292:Narcotic Antagonists / Q000009:adverse effects*
chemical_list: D009292:Narcotic Antagonists; D002047:Buprenorphine