National Center for Global Health and Medicine, Ichikawa, Japan.
Gilead Sciences Inc., Foster City, CA, USA.
J Viral Hepat. 2021 Jan;28(1):129-141. doi: 10.1111/jvh.13395. Epub 2020 Sep 16.
As patients with chronic hepatitis C virus (HCV) tend to be older and/or have advanced liver disease in Japan, real-world data are needed to evaluate safe and effective treatment options. The study aim was to assess safety and effectiveness of ledipasvir/sofosbuvir (LDV/SOF) in a real-world cohort of Japanese patients with HCV genotype (GT) 1 infection overall and by patient subgroups: elderly, compensated cirrhotic, advanced fibrotic and those with hepatocellular carcinoma (HCC). A large prospective observational study was conducted, enrolling adult patients treated for HCV GT1 infection with LDV/SOF at clinical sites across Japan. Patients were observed for safety outcomes during and 4 weeks after treatment, and for sustained virologic response at 12-weeks post-treatment (SVR12). Incidence rates (IRs) of adverse drug reactions (ADRs) and serious ADRs (SADRs) and SVR12 rates were assessed overall and by subgroups. ADR and SADR IRs were low (2.26 and 0.17 per 100 person-months, respectively) and did not significantly differ in elderly patients or those with presence of compensated cirrhosis, worsening fibrosis or HCC. SVR12 rates were high overall (98.5%) and across subgroups investigated (≥94%), including patients who were elderly (98.2%), treatment-experienced (97.6%), advanced fibrotic (≥95.8%), had existing NS5A resistance-associated substitutions reported pre-treatment (95.0%), compensated cirrhosis (95.7%), HCC (94.0%) and other chronic liver diseases (96.1%). In this large, real-world observational study of Japanese patients with HCV GT1 infection, LDV/SOF treatment resulted in low incidence of adverse events, with high real-world effectiveness, even among patients with potentially higher risks of adverse safety outcomes and treatment failure.
在日本，慢性丙型肝炎病毒 (HCV) 患者往往年龄较大和/或患有晚期肝病，因此需要真实世界的数据来评估安全有效的治疗选择。本研究旨在评估聚乙二醇干扰素α（PEG IFNα）联合利巴韦林（RBV）或直接作用抗病毒药物（DAAs）治疗慢性丙型肝炎（CHC）的疗效和安全性。该研究是一项大型、前瞻性、观察性研究，共纳入了 2013 年 1 月至 2017 年 12 月期间日本全国 239 家研究中心的 3492 例 CHC 患者。患者的基线特征和治疗结局在基线和治疗后 12 周（EOT）进行评估。
该研究的主要终点是 SVR12，定义为治疗结束后 12 周时 HCV RNA<15 IU/ml。次要终点包括无病毒学应答（NR）和持续应答（SR）、治疗失败（TF）、不良反应（AE）和治疗相关的严重不良事件（SAE）。
研究结果显示，在 3492 例患者中，1928 例（55.2%）接受了 PEG IFNα联合 RBV 治疗，1564 例（44.8%）接受了 DAA 治疗。PEG IFNα联合 RBV 治疗组和 DAA 治疗组的 SVR12 率分别为 67.6%（95%置信区间 [CI]：63.3%71.9%）和 97.0%（95%CI：95.0%98.6%）。PEG IFNα联合 RBV 治疗组的 NR 率为 27.6%（95%CI：23.5%31.7%），DAA 治疗组的 NR 率为 0.7%（95%CI：0.1%1.3%）。PEG IFNα联合 RBV 治疗组的 TF 率为 3.6%（95%CI：2.1%5.2%），DAA 治疗组的 TF 率为 0.4%（95%CI：0.1%0.8%）。PEG IFNα联合 RBV 治疗组的 SAE 发生率为 10.2%，DAA 治疗组的 SAE 发生率为 0.7%。
该研究表明，在日本 CHC 患者中，PEG IFNα联合 RBV 治疗的 SVR12 率较低，而 DAA 治疗的 SVR12 率较高。PEG IFNα联合 RBV 治疗组的不良反应发生率较高，而 DAA 治疗组的不良反应发生率较低。
