Gregory M Lucas1, Alicia Young2, Deborah Donnell2, Paul Richardson3, Apinun Aramrattana4, Yiming Shao5, Yuhua Ruan5, Wei Liu6, Liping Fu7, Jun Ma7, David D Celentano8, David Metzger9, J Brooks Jackson3, David Burns10. 1. Johns Hopkins University School of Medicine, Department of Medicine, 1830 E. Monument St., Room 435A, Baltimore, MD 21287, United States. Electronic address: glucas@jhmi.edu. 2. Fred Hutchinson Cancer Research Center, Vaccine and Infectious Disease Division, 1100 Fairview Ave N, Seattle, WA 98109, United States. 3. Johns Hopkins School of Medicine, Department of Pathology, 600North Wolfe St., Baltimore, MD 21287, United States. 4. Chiang Mai University, Faculty of Medicine, Department of Family Medicine, 110 Intavaroros Road, Chiang Mai, Thailand. 5. 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. 6. Guangxi Centers for Disease Control and Prevention, Guangxi Center for HIV/AIDS Prevention and Control, No. 18 Jinzhou Road, Nanning 530028, Guangxi, China. 7. Xinjiang Autonomous Region Center for Disease Control and Prevention, Jianquanyi Street no. 380, Urumqi 830002, Xinjiang, China. 8. Johns Hopkins Bloomberg School of Public Health, Department of Epidemiology, 615 North Wolfe Street, Suite W6041, Baltimore, MD 21205, United States. 9. Department of Psychiatry, University of Pennsylvania, 3535 Market Street, Suite 4000, Philadelphia, PA, 19104, United States. 10. National Institute of Allergy and Infectious Diseases, Division of AIDS, Prevention Sciences Branch, 6700 B Rockledge Drive, Room 5121, Bethesda, MD 20892, United States.
Abstract
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.
RCT Entities:
BACKGROUND:Buprenorphine/naloxone (BUP/NX), an effective treatment for opioid dependence, has been implicated in hepatic toxicity. However, aspersons 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-MATparticipants. 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.
Authors: Michael P Bogenschutz; Patrick J Abbott; Robert Kushner; J Scott Tonigan; George E Woody Journal: J Addict Med Date: 2010-12 Impact factor: 3.702
Authors: Pamela Vergara-Rodriguez; Mary Jo Tozzi; Michael Botsko; Vijay Nandi; Frederick Altice; James E Egan; Patrick G O'Connor; Lynn E Sullivan; David A Fiellin Journal: J Acquir Immune Defic Syndr Date: 2011-03-01 Impact factor: 3.731
Authors: Gregory M Lucas; Geetha Beauchamp; Apinun Aramrattana; Yiming Shao; Wei Liu; Liping Fu; J Brooks Jackson; David D Celentano; Paul Richardson; David Metzger Journal: Int J Drug Policy Date: 2011-08-17
Authors: A Berson; A Gervais; D Cazals; N Boyer; F Durand; J Bernuau; P Marcellin; C Degott; D Valla; D Pessayre Journal: J Hepatol Date: 2001-02 Impact factor: 25.083
Authors: M Zuin; A Giorgini; C Selmi; P M Battezzati; C A Cocchi; A Crosignani; A Benetti; P Invernizzi; M Podda Journal: Dig Liver Dis Date: 2008-02-21 Impact factor: 4.088
Authors: Andrew J Saxon; Walter Ling; Maureen Hillhouse; Christie Thomas; Albert Hasson; Alfonso Ang; Geetha Doraimani; Gudaye Tasissa; Yuliya Lokhnygina; Jeff Leimberger; R Douglas Bruce; John McCarthy; Katharina Wiest; Paul McLaughlin; Richard Bilangi; Allan Cohen; George Woody; Petra Jacobs Journal: Drug Alcohol Depend Date: 2012-08-22 Impact factor: 4.492