Hepatitis after intravenous injection of sublingual buprenorphine in acute hepatitis C carriers: report of two cases of disappearance of viral replication after acute hepatitis.
OBJECTIVE
To report 2 cases of acute hepatitis related to intravenous administration of buprenorphine in hepatitis C-infected patients.


METHODS
Two patients, aged 33 and 50 years, respectively, who were hepatitis C virus (HCV) carriers were treated with sublingual buprenorphine 8 mg/day for addiction. Several years after initiation of buprenorphine, they were hospitalized because of clinical hepatitis with jaundice that developed after intravenous injection of buprenorphine. Serum alanine aminotransferase rose to 100 times the upper limit of normal (ULN) in the first patient and to 21 times the ULN in the second. As cofactors, the first patient had consumed alcohol, and the second patient took aspirin 600 mg in addition to the injection of buprenorphine 20 mg 4 days before the onset of jaundice. After stopping the intravenous injections, both patients continued sublingual buprenorphine therapy, with no relapse of hepatitis. Interestingly, in these 2 patients, buprenorphine-induced hepatitis was followed by the disappearance of HCV RNA.


CONCLUSIONS
Most cases of hepatotoxicity related to buprenorphine have occurred in hepatitis C-infected patients. The main mechanism for buprenorphine-induced hepatitis is a mitochondrial defect, exacerbated by cofactors with additional potential to induce mitochondria dysfunction (eg, HCV, alcohol, concomitant medications). According to the Naranjo probability scale, buprenorphine was found to be the probable cause of acute hepatitis in both patients. In addition, we assessed the relationship between intravenous buprenorphine and acute hepatitis using 2 scales for causality assessment of hepatotoxicity (the Council for International Organizations of Medical Sciences scale and the Maria & Victorino scale). The diagnosis of intravenous buprenorphine-induced hepatitis was classified as probable in both cases. In addition, these 2 cases illustrate that acute hepatitis in a carrier of chronic HCV may occasionally facilitate the clearance of virus.


CONCLUSIONS
Although buprenorphine is well tolerated when used at recommended sublingual doses, patients should be informed about the risk of acute hepatitis with misuse of the drug by the intravenous route. These cases illustrate that, in carriers of chronic HCV, acute hepatitis may modify the host's immunotolerance and facilitate clearance of the virus.
Peyrière
Hélène
H
Department of Medical Pharmacology and Toxicology, Lapeyronie Hospital, Montpellier, France. hpeyriere@chu-montpellier.fr
Tatem
Ludmilla
L
Bories
Camille
C
Pageaux
Georges-Philippe
GP
Blayac
Jean-Pierre
JP
Larrey
Dominique
D
D000208:Acute Disease; D000286:Administration, Sublingual; D000328:Adult; D002047:Buprenorphine / Q000008:administration & dosage* / Q000009:adverse effects*; D002353:Carrier State; D016174:Hepacivirus / Q000302:isolation & purification; D006526:Hepatitis C / Q000209:etiology*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D014779:Virus Replication
D009292:Narcotic Antagonists; D002047:Buprenorphine