Ishigami Masatoshi, Hayashi Kazuhiko, Honda Takashi, Kuzuya Teiji, Ishizu Yoji, Ishikawa Tetsuya, Nakano Isao, Urano Fumihiro, Kumada Takashi, Yoshioka Kentaro, Goto Hidemi, Hirooka Yoshiki
Department of Gastroenterology and Hepatology, School of Medicine, Nagoya University, Nagoya, Japan.
Department of Gastroenterology, Toyohashi Municipal Hospital, Toyohashi, Japan.
J Gastroenterol Hepatol. 2017 Nov;32(11):1879-1886. doi: 10.1111/jgh.13779.
In this study, we investigated the real-world data of the first approved interferon-free regimen in Japan: daclatasvir and asunaprevir in chronic hepatitis C patients with severe fibrosis.
Among 924 patients registered in our multicenter study, 535 patients were defined as having severe fibrosis with Fib-4 index ≧ 3.25 and were included in this study. We investigated antiviral effect and factors associated with sustained viral response 12 (SVR12), and the additional effects on serum α-fetoprotein and albumin levels by eradicating virus in patients who attained SVR were investigated. In statistical analysis, P < 0.05 was considered as significant levels.
Antiviral effect was lower in patients with severe fibrosis at 8 and 12 weeks after start of the treatment (96.3%, 97.1% with severe fibrosis vs 99.5%, 99.2% without severe fibrosis, P = 0.002 and P = 0.036, respectively), and more early relapse (SVR4; 90.4% with severe fibrosis vs 95.4% without fibrosis, P = 0.008) was seen in patients with severe fibrosis; however, there were no differences in SVR12 and SVR24. In the safety profiles, discontinuation rate due to liver injury (2.8% with severe fibrosis vs 3.3% without severe fibrosis) or other causes of discontinuation was not different between two groups. Serum α-fetoprotein significantly decreased, and serum albumin levels significantly increased as early as 4 weeks after the start of treatment.
Although the antiviral effect was slightly lower in patients with severe fibrosis compared with those without, treatment with daclatasvir and asunaprevir is basically an effective and well-tolerable treatment in these populations.
在本研究中，我们调查了日本首个获批的不含干扰素方案（在伴有严重肝纤维化的慢性丙型肝炎患者中使用的达卡他韦和阿舒瑞韦）的真实世界数据。
在我们多中心研究登记的924例患者中，535例患者被定义为Fib-4指数≥3.25的严重肝纤维化患者，并纳入本研究。我们调查了抗病毒效果以及与持续病毒学应答12周（SVR12）相关的因素，并研究了在实现SVR的患者中通过清除病毒对血清甲胎蛋白和白蛋白水平的额外影响。在统计分析中，P<0.05被视为显著水平。
治疗开始后8周和12周时，严重肝纤维化患者的抗病毒效果较低（严重肝纤维化患者分别为96.3%、97.1%，无严重肝纤维化患者为99.5%、99.2%，P分别为0.002和0.036），并且严重肝纤维化患者出现更多早期复发（SVR4；严重肝纤维化患者为90.4%，无肝纤维化患者为95.4%，P=0.008）；然而，SVR12和SVR24无差异。在安全性方面，两组因肝损伤导致的停药率（严重肝纤维化患者为2.8%，无严重肝纤维化患者为3.3%）或其他停药原因无差异。治疗开始后4周血清甲胎蛋白显著降低，血清白蛋白水平显著升高。
尽管与无严重肝纤维化患者相比，严重肝纤维化患者的抗病毒效果略低，但在这些人群中，使用达卡他韦和阿舒瑞韦治疗基本上是一种有效且耐受性良好的治疗方法。
