Sun Junyi, Yang Mengzhao, Su Guanyue, Wang Ling, Hu Xiaobo, Zhou Yongjian, Cui Guangying, Qian Guowu, Yuan Yiqiang, Hu Xinjun, Li Silin, Luo Hong, Zhang Shixi, Li Guangming, Zhang Donghua, Li Guotao, Cheng Ming, Yu Zujiang, Ren Zhigang
Department of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Department of Cardiovascular Medicine, Henan Provincial Chest Hospital Affiliated to Zhengzhou University, Zhengzhou, 450008, China.
Adv Sci (Weinh). 2025 Apr;12(15):e2405679. doi: 10.1002/advs.202405679. Epub 2025 Feb 22.
Despite azvudine being prioritized for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, its effectiveness and safety remain inadequately substantiated in hospitalized SARS-CoV-2 infected patients with liver diseases. A retrospective nine-center cohort study along with an independent validation cohort is conducted to examine the efficacy of azvudine (Clinical Trial Registration Number: NCT06349655). The primary outcome is all-cause mortality and the secondary outcome is composite disease progression. Efficacy is assessed via Kaplan-Meier analysis and Cox regression, with subgroup and sensitivity analyses for further validation. Among 32 864 hospitalized SARS-CoV-2 infected patients, 1022 eligible azvudine recipients, and 1022 controls are included through propensity score match. Kaplan-Meier analysis reveals that azvudine treatment is associated with a lower risk of all-cause mortality and composite disease progression (both p<0.0001). Cox regression analysis suggests azvudine recipients could have a 39% lower risk of all-cause mortality than controls (95% confidence interval [CI]: 0.468-0.795, p<0.001), but with no notable significance in composite disease progression (hazard ratio: 0.85, 95% CI: 0.686-1.061, p = 0.154). Subgroup analysis suggests that azvudine has a greater benefit for both all-cause mortality and composite disease progression in patients with kidney diseases or without autoimmune diseases. Three sensitivity analyses and validation cohorts confirm the robustness of the findings. Safety analysis observes few adverse events in azvudine recipients. Within 15 days after azvudine administration, no significant difference in liver function indexes and kidney function indexes is observed between the two groups except for a few time points. These findings demonstrate that azvudine shows potential clinical efficacy in improving all-cause mortality in hospitalized SARS-CoV-2 infected patients with liver diseases, with acceptable adverse effects.
尽管阿兹夫定被优先用于治疗严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染，但其在住院的合并肝脏疾病的SARS-CoV-2感染患者中的有效性和安全性仍未得到充分证实。开展了一项回顾性九中心队列研究以及一个独立验证队列，以检验阿兹夫定的疗效（临床试验注册号：NCT06349655）。主要结局是全因死亡率，次要结局是复合疾病进展。通过Kaplan-Meier分析和Cox回归评估疗效，并进行亚组分析和敏感性分析以进一步验证。在32864例住院的SARS-CoV-2感染患者中，通过倾向得分匹配纳入了1022例符合条件的阿兹夫定接受者和1022例对照。Kaplan-Meier分析显示，阿兹夫定治疗与较低的全因死亡率和复合疾病进展风险相关（均p<0.0001）。Cox回归分析表明，阿兹夫定接受者的全因死亡率风险比对照低39%（95%置信区间[CI]：0.468-0.795，p<0.001），但在复合疾病进展方面无显著差异（风险比：0.85，95%CI：0.686-1.061，p = 0.154）。亚组分析表明，阿兹夫定在合并肾脏疾病或无自身免疫性疾病的患者中，对全因死亡率和复合疾病进展均有更大益处。三项敏感性分析和验证队列证实了研究结果的稳健性。安全性分析观察到阿兹夫定接受者中不良事件较少。在阿兹夫定给药后15天内，除少数时间点外，两组之间肝功能指标和肾功能指标无显著差异。这些研究结果表明，阿兹夫定在改善住院的合并肝脏疾病的SARS-CoV-2感染患者的全因死亡率方面显示出潜在的临床疗效，且不良反应可接受。
