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

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...

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Main Authors: Lucas G., Young A., Donnell D., Richardson P., Aramrattana A., Shao Y., Ruan Y., Liu W., Fu L., Ma J., Celentano D., Metzger D., Jackson J., Burns D.
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Published: Elsevier Ireland Ltd 2015
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spelling th-cmuir.6653943832-382922015-06-16T07:46:52Z 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 Lucas G. Young A. Donnell D. Richardson P. Aramrattana A. Shao Y. Ruan Y. Liu W. Fu L. Ma J. Celentano D. Metzger D. Jackson J. Burns D. Toxicology Pharmacology Pharmacology (medical) Psychiatry and Mental Health 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. © 2014 Elsevier Ireland Ltd. 2015-06-16T07:46:52Z 2015-06-16T07:46:52Z 2014-09-01 Article 03768716 2-s2.0-84905565999 10.1016/j.drugalcdep.2014.06.013 http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84905565999&origin=inward http://cmuir.cmu.ac.th/handle/6653943832/38292 Elsevier Ireland Ltd
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
topic Toxicology
Pharmacology
Pharmacology (medical)
Psychiatry and Mental Health
spellingShingle Toxicology
Pharmacology
Pharmacology (medical)
Psychiatry and Mental Health
Lucas G.
Young A.
Donnell D.
Richardson P.
Aramrattana A.
Shao Y.
Ruan Y.
Liu W.
Fu L.
Ma J.
Celentano D.
Metzger D.
Jackson J.
Burns D.
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
description 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. © 2014 Elsevier Ireland Ltd.
format Article
author Lucas G.
Young A.
Donnell D.
Richardson P.
Aramrattana A.
Shao Y.
Ruan Y.
Liu W.
Fu L.
Ma J.
Celentano D.
Metzger D.
Jackson J.
Burns D.
author_facet Lucas G.
Young A.
Donnell D.
Richardson P.
Aramrattana A.
Shao Y.
Ruan Y.
Liu W.
Fu L.
Ma J.
Celentano D.
Metzger D.
Jackson J.
Burns D.
author_sort Lucas G.
title 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
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
publisher Elsevier Ireland Ltd
publishDate 2015
url http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84905565999&origin=inward
http://cmuir.cmu.ac.th/handle/6653943832/38292
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