British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.
Department of Emergency Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
JAMA Netw Open. 2022 Jan 4;5(1):e2143050. doi: 10.1001/jamanetworkopen.2021.43050.
Initiation of injection drug use may be more frequent among people dispensed prescription opioid therapy for noncancer pain, potentially increasing the risk of hepatitis C virus (HCV) acquisition.
To assess the association between medically dispensed long-term prescription opioid therapy for noncancer pain and HCV seroconversion among individuals who were initially injection drug use-naive.
DESIGN, SETTING, AND PARTICIPANTS: A population-based, retrospective cohort study of individuals tested for HCV in British Columbia, Canada, with linkage to outpatient pharmacy dispensations, was conducted. Individuals with an initial HCV-negative test result followed by 1 additional test between January 1, 2000, and December 31, 2017, and who had no history of substance use at baseline (first HCV-negative test), were included. Participants were followed up from baseline to the last HCV-negative test or estimated date of seroconversion (midpoint between HCV-positive and the preceding HCV-negative test).
Episodes of prescription opioid use for noncancer pain were defined as acute (<90 days) or long-term (≥90 days). Prescription opioid exposure status (long-term vs prescription opioid-naive/acute) was treated as time-varying in survival analyses. In secondary analyses, long-term exposure was stratified by intensity of use (chronic vs. episodic) and by average daily dose in morphine equivalents (MEQ).
Multivariable Cox regression models were used to assess the association between time-varying prescription opioid status and HCV seroconversion.
A total of 382 478 individuals who had more than 1 HCV test were included, of whom more than half were female (224 373 [58.7%]), born before 1974 (201 944 [52.8%]), and younger than 35 years at baseline (196 298 [53.9%]). Participants were followed up for 2 057 668 person-years and 1947 HCV seroconversions occurred. Of the participants, 41 755 people (10.9%) were exposed to long-term prescription opioid therapy at baseline or during follow-up. The HCV seroconversion rate per 1000 person-years was 0.8 among the individuals who were prescription opioid-naive/acute (1489 of 1947 [76.5%] seroconversions; 0.4% seroconverted within 5 years) and 2.1 with long-term prescription opioid therapy (458 of 1947 [23.5%] seroconversions; 1.1% seroconverted within 5 years). In multivariable analysis, exposure to long-term prescription opioid therapy was associated with a 3.2-fold (95% CI, 2.9-3.6) higher risk of HCV seroconversion (vs prescription opioid-naive/acute). In separate Cox models, long-term chronic use was associated with a 4.7-fold higher risk of HCV seroconversion (vs naive/acute use 95% CI, 3.9-5.8), and long-term higher-dose use (≥90 MEQ) was associated with a 5.1-fold higher risk (vs naive/acute use 95% CI, 3.7-7.1).
In this cohort study of people with more than 1 HCV test, long-term prescription opioid therapy for noncancer pain was associated with a higher risk of HCV seroconversion among individuals who were injection drug use-naive at baseline or at prescription opioid initiation. These results suggest injection drug use initiation risk is higher among people dispensed long-term therapy and may be useful for informing approaches to identify and prevent HCV infection. These findings should not be used to justify abrupt discontinuation of long-term therapy, which could increase risk of harms.
起始使用注射毒品可能在接受非癌症疼痛的处方阿片类药物治疗的人群中更为频繁,这可能会增加丙型肝炎病毒(HCV)感染的风险。
评估在最初未使用注射毒品的人群中,长期开具处方阿片类药物治疗非癌症疼痛与 HCV 血清转换之间的关联。
设计、设置和参与者:对加拿大不列颠哥伦比亚省接受 HCV 检测的个体进行了一项基于人群的回顾性队列研究,并与门诊药房配药进行了链接。纳入了首次 HCV 阴性检测结果后,在 2000 年 1 月 1 日至 2017 年 12 月 31 日之间进行了另外一次检测,并且在基线时(首次 HCV 阴性检测)没有药物使用史的个体。从基线开始对参与者进行随访,直至最后一次 HCV 阴性检测或估计的血清转换日期(HCV 阳性和前一次 HCV 阴性检测之间的中点)。
非癌症疼痛的阿片类药物使用发作被定义为急性(<90 天)或长期(≥90 天)。处方阿片类药物暴露状况(长期与处方阿片类药物未使用/急性)在生存分析中被视为时间变化。在二次分析中,长期暴露按使用强度(慢性与发作性)和吗啡当量(MEQ)的平均日剂量进行分层。
使用多变量 Cox 回归模型评估时间变化的处方阿片类药物状态与 HCV 血清转换之间的关联。
共纳入了 382478 名接受了多次 HCV 检测的个体,其中超过一半为女性(224373 [58.7%]),出生于 1974 年之前(201944 [52.8%]),并且基线时年龄小于 35 岁(196298 [53.9%])。参与者接受了 2057668 人年的随访,发生了 1947 例 HCV 血清转换。在参与者中,41755 人(10.9%)在基线或随访期间接受了长期处方阿片类药物治疗。每 1000 人年的 HCV 血清转换率在未使用阿片类药物/急性(1947 例中的 1489 例[76.5%];5 年内有 0.4%发生血清转换)和长期处方阿片类药物治疗(1947 例中的 458 例[23.5%];5 年内有 1.1%发生血清转换)之间存在差异。在多变量分析中,长期接受处方阿片类药物治疗与 HCV 血清转换的风险增加 3.2 倍(95%CI,2.9-3.6)(与未使用阿片类药物/急性相比)。在单独的 Cox 模型中,长期慢性使用与 HCV 血清转换的风险增加 4.7 倍(95%CI,3.9-5.8),长期高剂量使用(≥90 MEQ)与 HCV 血清转换的风险增加 5.1 倍(95%CI,3.7-7.1)。
在这项对多次 HCV 检测的人群进行的队列研究中,长期开具非癌症疼痛的处方阿片类药物治疗与基线或起始处方阿片类药物治疗时未使用注射毒品的个体发生 HCV 血清转换的风险增加相关。这些结果表明,起始使用注射毒品的风险在接受长期治疗的人群中更高,这可能有助于确定和预防 HCV 感染。这些发现不应被用来证明突然停止长期治疗是合理的,因为这可能会增加伤害的风险。