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

doi:10.1016/j.drugalcdep.2014.06.013

Back

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

Journal article

Open access

Peer reviewed

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, …

Drug and alcohol dependence, Vol.142, pp.139-145

09/01/2014

DOI: 10.1016/j.drugalcdep.2014.06.013

PMCID: PMC4127183

PMID: 24999060

Files and links (1)

url

http://doi.org/10.1016/j.drugalcdep.2014.06.013View

Open Access

Abstract

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. 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. 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. 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.

HIV Prevention

Safety

Injection drug use

Buprenorphine/naloxone

Opioid dependence

Alanine aminotransferase

Hepatitis C virus

Hepatotoxicity

Details

Title: Subtitle: 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
Creators: Gregory M Lucas - Johns Hopkins University School of Medicine, Department of Medicine, 1830 E. Monument St., Room 435A, Baltimore, MD 21287, United States
Alicia Young - Fred Hutchinson Cancer Research Center, Vaccine and Infectious Disease Division, 1100 Fairview Ave N, Seattle, WA 98109, United States
Deborah Donnell - Fred Hutchinson Cancer Research Center, Vaccine and Infectious Disease Division, 1100 Fairview Ave N, Seattle, WA 98109, United States
Paul Richardson - Johns Hopkins School of Medicine, Department of Pathology, 600North Wolfe St., Baltimore, MD 21287, United States
Apinun Aramrattana - Chiang Mai University, Faculty of Medicine, Department of Family Medicine, 110 Intavaroros Road, Chiang Mai, Thailand
Yiming Shao - State Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing, China
Yuhua Ruan - State Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing, China
Wei Liu - Guangxi Center for Disease Prevention and Control
Liping Fu - Xinjiang Autonomous Region Center for Disease Control and Prevention, Jianquanyi Street no. 380, Urumqi 830002, Xinjiang, China
Jun Ma - Xinjiang Autonomous Region Center for Disease Control and Prevention, Jianquanyi Street no. 380, Urumqi 830002, Xinjiang, China
David D Celentano - Johns Hopkins Bloomberg School of Public Health, Department of Epidemiology, 615 North Wolfe Street, Suite W6041, Baltimore, MD 21205, United States
David Metzger - Department of Psychiatry, University of Pennsylvania, 3535 Market Street, Suite 4000, Philadelphia, PA, 19104, United States
J. Brooks Jackson - Johns Hopkins School of Medicine, Department of Pathology, 600North Wolfe St., Baltimore, MD 21287, United States
David Burns - National Institute of Allergy and Infectious Diseases, Division of AIDS, Prevention Sciences Branch, 6700 B Rockledge Drive, Room 5121, Bethesda, MD 20892, United States
Resource Type: Journal article
Publication Details: Drug and alcohol dependence, Vol.142, pp.139-145
DOI: 10.1016/j.drugalcdep.2014.06.013
PMID: 24999060
PMCID: PMC4127183
NLM abbreviation: Drug Alcohol Depend
ISSN: 0376-8716
eISSN: 1879-0046
Publisher: Elsevier Ireland Ltd
Grant note: DOI: 10.13039/501100002842, name: Chiang Mai University
Language: English
Date published: 09/01/2014
Academic Unit: Pathology; VPMA - Administration
Record Identifier: 9984047741202771

Metrics

18 Record Views

6 Times Cited - Web of Science