Tetrault Jeanette M, Tate Janet P, Edelman E Jennifer, Gordon Adam J, Lo Re Vincent, Lim Joseph K, Rimland David, Goulet Joseph, Crystal Stephen, Gaither Julie R, Gibert Cynthia L, Rodriguez-Barradas Maria C, Fiellin Lynn E, Bryant Kendall, Justice Amy C, Fiellin David A
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT.
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT; VA Connecticut Health Care System, West Haven, CT.
J Subst Abuse Treat. 2016 Sep;68:62-7. doi: 10.1016/j.jsat.2016.06.002. Epub 2016 Jun 6.
Individuals with HIV and hepatitis C (HCV) infection, alcohol use disorder, or who are prescribed potentially hepatotoxic medications may be at increased risk for buprenorphine (BUP) associated hepatotoxicity.
We examined a cohort of HIV-infected and uninfected patients receiving an initial BUP prescription between 2003 and 2012. We compared changes in alanine and aspartate aminotransferases (ALT and AST) and total bilirubin (TB) stratified by HIV status. We identified cases of liver enzyme elevation (LEE), TB elevation (TBE), and conducted chart review to assess for cases of drug induced liver injury (DILI) and death. We examined associations between age, sex, race, HIV-infection, HCV-infection, alcohol use disorder, and prescription of other potentially heptatotoxic medications with the composite endpoint of LEE, TBE, and DILI.
Of 666 patients prescribed BUP, 36% were HIV-infected, 98% were male, 60% had RNA-confirmed HCV infection, 50% had a recent diagnosis of alcohol use disorder, and 64% were prescribed other potentially hepatotoxic medications. No clinically significant changes were observed in median ALT, AST and TB and these changes did not differ between HIV-infected and uninfected patients. Compared with uninfected patients, HIV-infected (OR 7.3, 95% CI 2.1-26.1, p=0.002), HCV-infected (OR 4.9 95% CI 1.6-15.2, p=0.007) or HIV/HCV co-infected patients (OR 6.9, 95%CI 2.1-22.2, p=0.001) were more likely to have the composite endpoint of LEE, TB elevation or DILI, in analyses that excluded 60 patients with evidence of pre-existing liver injury. 31 patients had LEE, 14/187 HIV-infected and 17/340 uninfected (p=0.25); 11 had TBE, including 9/186 HIV-infected and 2/329 uninfected (p=0.002); 8 experienced DILI, 4/202 HIV-infected and 4/204 uninfected (p=0.45). There were no significant associations with alcohol use disorder or prescription of other potentially hepatotoxic medications after adjustment for HIV/HCV status.
Liver enzymes and TB are rarely elevated in HIV-infected and uninfected patients receiving BUP. Risk of hepatotoxicity was greater in individuals infected with HIV, HCV, or HIV/HCV co-infection, who may benefit from increased monitoring.
感染人类免疫缺陷病毒(HIV)和丙型肝炎病毒(HCV)、患有酒精使用障碍或正在服用可能具有肝毒性药物的个体,可能面临丁丙诺啡(BUP)相关肝毒性风险增加的情况。
我们研究了一组在2003年至2012年间首次接受BUP处方的HIV感染和未感染患者。我们比较了按HIV状态分层的丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和总胆红素(TB)的变化。我们确定了肝酶升高(LEE)、TB升高(TBE)的病例,并进行病历审查以评估药物性肝损伤(DILI)和死亡病例。我们研究了年龄、性别、种族、HIV感染、HCV感染、酒精使用障碍以及其他潜在肝毒性药物处方与LEE、TBE和DILI复合终点之间的关联。
在666例开具BUP处方的患者中,36%为HIV感染者,98%为男性,6%经RNA确认感染HCV,50%近期诊断为酒精使用障碍,64%开具了其他潜在肝毒性药物。未观察到ALT、AST和TB中位数有临床显著变化,且HIV感染和未感染患者之间的这些变化无差异。与未感染患者相比,在排除60例有既往肝损伤证据的患者的分析中,HIV感染者(比值比[OR] 7.3,95%置信区间[CI] 2.1 - 26.1,p = 0.002)、HCV感染者(OR 4.9,95% CI 1.6 - 15.2,p = 0.007)或HIV/HCV合并感染者(OR 6.9,95% CI 2.1 - 22.2,p = 0.001)更有可能出现LEE、TB升高或DILI复合终点。31例患者出现LEE,其中14/187例为HIV感染者,17/340例为未感染者(p = 0.25);11例出现TBE,包括9/186例HIV感染者和2/329例未感染者(p = 0.002);8例发生DILI,4/2%例为HIV感染者,4/204例为未感染者(p = 0.45)。在调整HIV/HCV状态后,与酒精使用障碍或其他潜在肝毒性药物处方无显著关联。
接受BUP治疗的HIV感染和未感染患者中,肝酶和TB很少升高。HIV、HCV或HIV/HCV合并感染个体的肝毒性风险更大,他们可能受益于加强监测。