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Abstract：
UNASSIGNED: HCV infection is associated with mortality due to extrahepatic manifestations (EHM). Sustained virologic response (SVR) following direct-acting antiviral (DAA) therapy has been linked to decreased all-cause and liver-related mortality. However, evidence regarding the impact of DAA on EHM-related deaths is lacking. This study aimed to assess the impact of DAA and SVR on EHM-related mortality.
UNASSIGNED: The British Columbia Hepatitis Testers Cohort comprises ∼1.7 million people tested for HCV between 1990 and 2015 and is linked with administrative health data. Among individuals diagnosed with HCV by 12/31/2020, those who received at least one DAA treatment were matched to those who never received treatment by the year of their first HCV RNA positive date. We compared three groups: treated & SVR, treated & no-SVR, and untreated; and generated EHM mortality rates and incidence curves. To account for differences in baseline characteristics, we used inverse probability of treatment weights (IPTW). IPTW-weighted multivariable cause-specific Cox regression models were adjusted for competing risk and confounders.
UNASSIGNED: Study population included 12,815 treated (12,287 SVR, 528 no-SVR) and 12,815 untreated individuals (median follow-up 3.4 years, IQR 2.9). The untreated group had the highest EHM mortality rate (30.9 per 1000 person-years [PY], 95% CI 29.2-32.8), followed by the treated & no-SVR group (21.2 per 1000 PY, 95% CI 14.9-30.1), while the treated & SVR group had the lowest EHM mortality rate (7.9 per 1000 PY, 95% CI 7.1-8.7). In the multivariable model, EHM mortality in the treated & SVR group was significantly decreased (adjusted cause-specific hazard ratio [acsHR] 0.20, 95% CI 0.18-0.23). The treated & SVR group had significant reductions in mortality related to each of the EHMs (78-84%).
UNASSIGNED: Treatment of HCV with DAA was associated with significant reductions in EHM-related mortality. These findings emphasize the critical importance of timely diagnosis and treatment of HCV to prevent deaths associated with EHM, and have important implications for clinical practice and public health.
UNASSIGNED: This work was supported by the BC Centre for Disease Control and the Canadian Institutes of Health Research (CIHR) [Grant # NHC-348216, PJT-156066, and PHE-337680]. DJ has received Doctoral Research Award (#201910DF1-435705-64343) from the Canadian Institutes of Health Research (CIHR) and Doctoral fellowship from the Canadian Network on Hepatitis C (CanHepC). CanHepC is funded by a joint initiative of the Canadian Institutes of Health Research (CIHR) (NHC-142832) and the Public Health Agency of Canada (PHAC).
UNASSIGNED: The British Columbia Hepatitis Testers Cohort comprises ∼1.7 million people tested for HCV between 1990 and 2015 and is linked with administrative health data. Among individuals diagnosed with HCV by 12/31/2020, those who received at least one DAA treatment were matched to those who never received treatment by the year of their first HCV RNA positive date. We compared three groups: treated & SVR, treated & no-SVR, and untreated; and generated EHM mortality rates and incidence curves. To account for differences in baseline characteristics, we used inverse probability of treatment weights (IPTW). IPTW-weighted multivariable cause-specific Cox regression models were adjusted for competing risk and confounders.
UNASSIGNED: Study population included 12,815 treated (12,287 SVR, 528 no-SVR) and 12,815 untreated individuals (median follow-up 3.4 years, IQR 2.9). The untreated group had the highest EHM mortality rate (30.9 per 1000 person-years [PY], 95% CI 29.2-32.8), followed by the treated & no-SVR group (21.2 per 1000 PY, 95% CI 14.9-30.1), while the treated & SVR group had the lowest EHM mortality rate (7.9 per 1000 PY, 95% CI 7.1-8.7). In the multivariable model, EHM mortality in the treated & SVR group was significantly decreased (adjusted cause-specific hazard ratio [acsHR] 0.20, 95% CI 0.18-0.23). The treated & SVR group had significant reductions in mortality related to each of the EHMs (78-84%).
UNASSIGNED: Treatment of HCV with DAA was associated with significant reductions in EHM-related mortality. These findings emphasize the critical importance of timely diagnosis and treatment of HCV to prevent deaths associated with EHM, and have important implications for clinical practice and public health.
UNASSIGNED: This work was supported by the BC Centre for Disease Control and the Canadian Institutes of Health Research (CIHR) [Grant # NHC-348216, PJT-156066, and PHE-337680]. DJ has received Doctoral Research Award (#201910DF1-435705-64343) from the Canadian Institutes of Health Research (CIHR) and Doctoral fellowship from the Canadian Network on Hepatitis C (CanHepC). CanHepC is funded by a joint initiative of the Canadian Institutes of Health Research (CIHR) (NHC-142832) and the Public Health Agency of Canada (PHAC).
摘要：
■HCV感染与由于肝外表现（EHM）引起的死亡率相关。直接作用抗病毒（DAA）治疗后的持续病毒学应答（SVR）与降低全因和肝脏相关死亡率有关。然而,缺乏关于DAA对EHM相关死亡影响的证据.本研究旨在评估DAA和SVR对EHM相关死亡率的影响。
■不列颠哥伦比亚省肝炎测试仪队列包括1990年至2015年间进行HCV测试的约170万人，并与行政健康数据相关联。在2020年12月31日之前诊断为HCV的个体中，接受至少一种DAA治疗的个体与在第一次HCVRNA阳性日期之前从未接受过治疗的个体相匹配。我们比较了三组：治疗和SVR，治疗和无SVR，和未经治疗；并产生EHM死亡率和发病率曲线。为了说明基线特征的差异，我们使用治疗权重的逆概率(IPTW)。IPTW加权多变量原因特异性Cox回归模型针对竞争风险和混杂因素进行了调整。
■研究人群包括12,815人接受治疗（12,287SVR，528个无SVR）和12,815个未经治疗的个体（中位随访3.4年，IQR2.9).未经治疗组的EHM死亡率最高（每1000人年30.9[PY]，95%CI29.2-32.8），其次是治疗和无SVR组(21.2/1000PY，95%CI14.9-30.1），而治疗组和SVR组的EHM死亡率最低（7.9/1000PY，95%CI7.1-8.7）。在多变量模型中，治疗组和SVR组的EHM死亡率显着降低（校正的原因特异性风险比[acsHR]0.20，95％CI0.18-0.23）。治疗&SVR组有与每个EHM相关的死亡率显著降低(78-84%)。
■用DAA治疗HCV与EHM相关死亡率显著降低相关。这些发现强调了及时诊断和治疗HCV以预防与EHM相关的死亡的重要性。并对临床实践和公共卫生具有重要意义。
■这项工作得到了不列颠哥伦比亚省疾病控制中心和加拿大卫生研究院（CIHR）[授予#NHC-348216、PJT-156066和PHE-337680]的支持。DJ已获得加拿大健康研究所（CIHR）的博士研究奖（＃201910DF1-435705-64343）和加拿大丙型肝炎网络（CanHepC）的博士奖学金。CanHepC由加拿大卫生研究院（CIHR）（NHC-142832）和加拿大公共卫生署（PHAC）的联合倡议资助。
■不列颠哥伦比亚省肝炎测试仪队列包括1990年至2015年间进行HCV测试的约170万人，并与行政健康数据相关联。在2020年12月31日之前诊断为HCV的个体中，接受至少一种DAA治疗的个体与在第一次HCVRNA阳性日期之前从未接受过治疗的个体相匹配。我们比较了三组：治疗和SVR，治疗和无SVR，和未经治疗；并产生EHM死亡率和发病率曲线。为了说明基线特征的差异，我们使用治疗权重的逆概率(IPTW)。IPTW加权多变量原因特异性Cox回归模型针对竞争风险和混杂因素进行了调整。
■研究人群包括12,815人接受治疗（12,287SVR，528个无SVR）和12,815个未经治疗的个体（中位随访3.4年，IQR2.9).未经治疗组的EHM死亡率最高（每1000人年30.9[PY]，95%CI29.2-32.8），其次是治疗和无SVR组(21.2/1000PY，95%CI14.9-30.1），而治疗组和SVR组的EHM死亡率最低（7.9/1000PY，95%CI7.1-8.7）。在多变量模型中，治疗组和SVR组的EHM死亡率显着降低（校正的原因特异性风险比[acsHR]0.20，95％CI0.18-0.23）。治疗&SVR组有与每个EHM相关的死亡率显著降低(78-84%)。
■用DAA治疗HCV与EHM相关死亡率显著降低相关。这些发现强调了及时诊断和治疗HCV以预防与EHM相关的死亡的重要性。并对临床实践和公共卫生具有重要意义。
■这项工作得到了不列颠哥伦比亚省疾病控制中心和加拿大卫生研究院（CIHR）[授予#NHC-348216、PJT-156066和PHE-337680]的支持。DJ已获得加拿大健康研究所（CIHR）的博士研究奖（＃201910DF1-435705-64343）和加拿大丙型肝炎网络（CanHepC）的博士奖学金。CanHepC由加拿大卫生研究院（CIHR）（NHC-142832）和加拿大公共卫生署（PHAC）的联合倡议资助。
