Buprenorphine/Naloxone and methadone effects on laboratory indices of liver health: a randomized trial

Drug Alcohol Depend. 2013 Feb 1;128(1-2):71-6. doi: 10.1016/j.drugalcdep.2012.08.002. Epub 2012 Aug 22.


Background: Buprenorphine/naloxone (BUP) and methadone (MET) are efficacious treatments for opioid dependence, although concerns about a link between BUP and drug-induced hepatitis have been raised. This study compares the effects of BUP and MET on liver health in opioid-dependent participants.

Methods: This was a randomized controlled trial of 1269 opioid-dependent participants seeking treatment at 8 federally licensed opioid treatment programs and followed for up to 32 weeks between May 2006 and August 2010; 731 participants met "evaluable" criteria defined as completing 24 weeks of medication and providing at least 4 blood samples for transaminase testing. Participants were randomly assigned to receive BUP or MET for 24 weeks. Shift table analysis determined how many evaluable participants moved between categories of low and elevated transaminase levels. Predictors of moving from low to high transaminase levels were identified.

Results: Changes in transaminase levels did not differ by medication condition. Baseline infection with hepatitis C or B was the only significant predictor of moving from low to elevated transaminase levels; 9 BUP and 15 MET participants showed extreme liver test elevations and were more likely than those without extreme elevations to have seroconverted to both hepatitis B and C during the study, or to use illicit drugs during the first 8 weeks of treatment. MET participants were retained longer in treatment than BUP participants.

Conclusions: This study demonstrated no evidence of liver damage during the initial 6 months of treatment in either condition. Physicians can prescribe either medication without major concern for liver injury.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Buprenorphine / adverse effects*
  • Buprenorphine / therapeutic use
  • Chemical and Drug Induced Liver Injury / blood
  • Chemical and Drug Induced Liver Injury / diagnosis
  • Chemical and Drug Induced Liver Injury / etiology*
  • Drug Combinations
  • Female
  • Humans
  • Liver / drug effects*
  • Male
  • Methadone / adverse effects*
  • Methadone / therapeutic use
  • Middle Aged
  • Naloxone / adverse effects*
  • Naloxone / therapeutic use
  • Opioid-Related Disorders / blood
  • Opioid-Related Disorders / drug therapy*
  • Transaminases / blood
  • Treatment Outcome


  • Drug Combinations
  • Naloxone
  • Buprenorphine
  • Transaminases
  • Methadone