Hepatotoxicity in a 52-week randomized trial of short-term versus long-term treatment with buprenorphine/naloxone in HIV-negative injection opioid users in China and Thailand

Gregory M. Lucas, Alicia Young, Deborah Donnell, Paul Richardson, Apinun Aramrattana, Yiming Shao, Yuhua Ruan, Wei Liu, Liping Fu, Jun Ma, David D. Celentano, David Metzger, J. Brooks Jackson, David Burns

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Background: Buprenorphine/naloxone (BUP/NX), an effective treatment for opioid dependence, has been implicated in hepatic toxicity. However, as persons taking BUP/NX have multiple hepatic risk factors, comparative data are needed to quantify the risk of hepatoxicity with BUP/NX. Methods: We compared rates of alanine aminotransferase (ALT) elevation. ≥. grade 3 (ALT. ≥. 5.1 times the upper limit of normal) and graded bilirubin elevations in HIV-negative opioid injectors randomized to long-term (52 weeks) or short-term (18 days) medication assisted treatment (LT-MAT and ST-MAT, respectively) with BUP/NX in a multisite trial conducted in China and Thailand. ALT and bilirubin were measured at baseline, 12, 26, 40 and 52 weeks, times temporally remote from BUP/NX exposure in the ST-MAT participants. Results: Among1036 subjects with at least one laboratory follow-up measurement, 76 (7%) participants experienced ALT elevation. ≥. grade 3. In an intent-to-treat analysis, the risk of ALT events was similar in participants randomized to LT-MAT compared with ST-MAT (adjusted hazard ratio 1.25, 95% confidence interval 0.79 to 1.98). This finding was supported by an as-treated analysis, in which actual exposure to BUP/NX was considered. Hepatitis C seroconversion during follow-up was strongly associated with ALT events. Bilirubin elevations. ≥. grade 2 occurred in 2% of subjects, with no significant difference between arms. Conclusions: Over 52-week follow-up, the risk of hepatotoxicity was similar in opioid injectors receiving brief and prolonged treatment with BUP/NX. These data suggest that most hepatotoxic events observed during treatment with BUP/NX are due to other factors.

Original languageEnglish (US)
Pages (from-to)139-145
Number of pages7
JournalDrug and alcohol dependence
StatePublished - Sep 1 2014

Bibliographical note

Funding Information:
This study was funded by the HIV Prevention Trials Network (HPTN) and sponsored by the National Institute of Allergy and Infectious Diseases , National Institute on Drug Abuse , National Institute of Mental Health , and Office of AIDS Research , of the National Institutes of Health , U.S. Department of Health and Human Services under award numbers UM1 AI068619 , UO1 AI068613 , and UM1 AI068613 . GML was supported by the National Institute on Drug Abuse ( K24 DA035684 ) and by the Johns Hopkins Center for AIDS Research (P30 AI094189). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health . The buprenorphine/naloxone (Suboxone) used in the trial was provided by Reckitt Benckiser Pharmaceuticals, Inc. The National Institutes of Health and participating manufacturer had no further role in the study design; in the collection, analysis, or interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication.


  • Alanine aminotransferase
  • Buprenorphine/naloxone
  • HIV prevention
  • Hepatitis C virus
  • Hepatotoxicity
  • Injection drug use
  • Opioid dependence
  • Safety


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