Hepatitis after intravenous buprenorphine misuse in heroin addicts.
BACKGROUND
Sublingual buprenorphine is used as a substitution drug in heroin addicts. Although buprenorphine inhibits mitochondrial function at high concentrations in experimental animals, these effects should not occur after therapeutic sublingual doses, which give very low plasma concentrations.


METHODS
We report four cases of former heroin addicts infected with hepatitis C virus and placed on substitution therapy with buprenorphine. These patients exhibited a marked increase in serum alanine amino transferase (30-, 37-, 13- and 50-times the upper limit of normal, respectively) after injecting buprenorphine intravenously and three of them also became jaundiced. Interruption of buprenorphine injections was associated with prompt recovery, even though two of these patients continued buprenorphine by the sublingual route. A fifth patient carrying the hepatitis C and human immunodeficiency viruses, developed jaundice and asterixis with panlobular liver necrosis and microvesicular steatosis after using sublingual buprenorphine and small doses of paracetamol and aspirin.


CONCLUSIONS
Although buprenorphine hepatitis is most uncommon even after intravenous misuse, addicts placed on buprenorphine substitution should be repeatedly warned not to use it intravenously. Higher drug concentrations could trigger hepatitis in a few intravenous users, possibly those whose mitochondrial function is already impaired by viral infections and other factors.
INSERM U1481 and Service d'Hépatologie, H pital Beaujon, Clichy, France.
A
A
Berson
A
A
Gervais
D
D
Cazals
N
N
Boyer
F
F
Durand
J
J
Bernuau
P
P
Marcellin
C
C
Degott
D
D
Valla
D
D
Pessayre
D000286:Administration, Sublingual; D000328:Adult; D000818:Animals; D002047:Buprenorphine / Q000008:administration & dosage / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000473:pathology; D015658:HIV Infections / Q000150:complications; D006526:Hepatitis C / Q000150:complications; D006556:Heroin Dependence / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D009294:Narcotics / Q000008:administration & dosage / Q000633:toxicity*
D009294:Narcotics; D002047:Buprenorphine