Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
J Gastroenterol. 2013 Feb;48(2):254-68. doi: 10.1007/s00535-012-0631-y. Epub 2012 Jul 12.
Pegylated interferon (PEG-IFN) plus ribavirin (RBV) therapy is the current standard of care for patients with chronic hepatitis C. Determining precisely the risk of serious adverse events (SAEs) and mortality from a single study is rather difficult because of the infrequency of such events. The aim of this systematic review was to assess the rates of SAEs and the mortality of PEG-IFN/RBV therapy in a pooled large sample, and to assess the relationship between SAEs and mortality rates and therapeutic characteristics.
A literature search was conducted using MEDLINE, EMBASE, and the Cochrane Library to identify randomized controlled trials evaluating the efficacy and safety of PEG-IFN/RBV therapy. We calculated the crude mortality and SAE rates with 95% confidence intervals (CIs).
Eighty studies with 153 treatment arms that included 27569 patients were enrolled (14401 patients treated with Peg-IFN alpha-2a/RBV and 13168 with Peg-IFN alpha-2b/RBV). All-cause and treatment-related deaths were observed in 50 (0.18%; 95% confidence interval [CI] 0.13-0.24%) and sixteen (0.058%; 95% CI 0.033-0.094%) patients, respectively. The crude SAE rate was 7.08% (95% CI 6.75-7.41%). Subgroup analysis revealed higher SAE rates in patients receiving PEG-IFN alpha-2a than in those with PEG-IFN alpha-2b (7.45 vs. 6.74%), and higher SAE rates with higher doses than with the lower doses in PEG-IFN-2a and 2b (11.94 vs. 6.99%, 7.10 vs. 5.05%, respectively), and with extended duration (> 48 weeks) than with standard duration (48 weeks) (15.5 vs. 6.67%) in PEG-IFN alpha-2a.
The mortality rate during PEG-IFN/RBV therapy was acceptably low, but the rate of SAEs was not negligible in a treatment for a benign disease, and the rate was affected by treatment regimens.
聚乙二醇干扰素（PEG-IFN）联合利巴韦林（RBV）治疗是慢性丙型肝炎患者的当前标准治疗方法。由于此类事件的发生率较低，因此很难从单一研究中准确确定严重不良事件（SAE）和死亡率的风险。本系统评价的目的是评估聚乙二醇干扰素/RBV 治疗的 SAE 发生率和死亡率，并评估 SAE 与死亡率和治疗特征之间的关系。
使用 MEDLINE、EMBASE 和 Cochrane 图书馆进行文献检索，以确定评估 PEG-IFN/RBV 治疗疗效和安全性的随机对照试验。我们计算了 95%置信区间（CI）的粗死亡率和 SAE 率。
共纳入 80 项研究（153 个治疗组），共纳入 27569 例患者（14401 例接受 Peg-IFN alpha-2a/RBV 治疗，13168 例接受 Peg-IFN alpha-2b/RBV 治疗）。在所有原因和治疗相关死亡中，分别观察到 50 例（0.18%；95%CI 0.13-0.24%）和 16 例（0.058%；95%CI 0.033-0.094%）。粗 SAE 发生率为 7.08%（95%CI 6.75-7.41%）。亚组分析显示，接受 Peg-IFN alpha-2a 治疗的患者 SAE 发生率高于接受 Peg-IFN alpha-2b 治疗的患者（7.45%比 6.74%），高剂量与低剂量的 Peg-IFN-2a 和 2b 相比（11.94%比 6.99%，7.10%比 5.05%），以及与标准疗程（48 周）相比（15.5%比 6.67%），PEG-IFN alpha-2a 疗程延长（>48 周）（15.5%比 6.67%）。
PEG-IFN/RBV 治疗期间的死亡率可接受较低，但在治疗良性疾病时，SAE 的发生率并不低，且该发生率受治疗方案的影响。
