a Research and Hepatobiliary Tumor Program , The Liver Institute at Methodist Dallas Medical Center.
b Department of Internal Medicine , Methodist Dallas Medical Center.
Expert Rev Anti Infect Ther. 2016;14(2):157-65. doi: 10.1586/14787210.2016.1120668. Epub 2015 Dec 17.
Hepatitis C virus (HCV) affects nearly 1.3% of US population and around 2% of people worldwide. It is associated with serious complication of Cirrhosis and Hepatocellular carcinoma leading to significant morbidity and mortality. Until now the only treatment option for this serious disease was interferon based therapy which had poor tolerance and at best SVR (Sustained virological response) in only 50% of cases. With the introduction of other direct - acting antiviral agents the treatment of HCV has been revolutionized with significantly high rates of cure. Among novel Direct acting antivirals are non-nucleoside inhibitor NS5B which is highly effective in treatment of HCV genotype 1 a and 1b including those with compensated cirrhosis achieving high cure rates with SVR more than 97 % in pooled analysis from six different phase 3 trials. This review will discuss the DAA - Dasabuvir, a non - nucleoside NS5B inhibitor, its mechanism of action, efficacy, safety & tolerance, and drug resistance. Dasabuvir is approved by FDA in combination with other DAA agents called as the 3D(Viekira Pak) in various interferon free regimens achieving high cure rates (SVR >95%) with low adverse effects. In Europe, it is approved by European medicines agency for use in combination with Ombitasvir, Paritaprevir, and ritonavir with or without ribavirin. The drug is used in treatment naive as well as previously treated patient with high success rates. It is also approved in patients with compensated cirrhosis, patients with HIV co-infection and liver transplant recipients which were in the past were excluded from treatment with interferon based therapy. Dasabuvir is extensively evaluated in large clinical trials and shown excellent SVR among HCV genotype1 patient population in combination with other oral DAAs, with good safety profile and tolerance. Its drawback is its genotype restriction, need for ribavirin (RBV) for 1a genotype, low resistance barrier and high cost. It is well tolerated with less than 1 % of patients permanently discontinuing treatment and 2% of patient experiencing a serious adverse reaction. It is contraindicated in patients with known hypersensitivity to ritonavir (e.g. Steven - Johnson syndrome) and strong inducers of CYP3A and CYP2CB.
丙型肝炎病毒（HCV）影响了美国近 1.3%的人口和全球约 2%的人口。它与肝硬化和肝细胞癌的严重并发症有关，导致发病率和死亡率显著增加。到目前为止，这种严重疾病的唯一治疗选择是基于干扰素的治疗，但只有 50%的患者有良好的持续病毒学应答（SVR）。随着其他直接作用抗病毒药物的引入，丙型肝炎的治疗发生了革命性的变化，治愈率显著提高。新型直接作用抗病毒药物中有一种非核苷抑制剂 NS5B，对 HCV 基因型 1a 和 1b 的治疗非常有效，包括代偿性肝硬化患者，在六项不同的 3 期临床试验的汇总分析中，SVR 达到 97%以上，治愈率很高。本文将讨论直接作用抗病毒药物（DAA）-达沙布韦，一种非核苷 NS5B 抑制剂，其作用机制、疗效、安全性和耐受性以及耐药性。达沙布韦已获得 FDA 批准，与其他 DAA 药物联合使用（称为 3D[维帕他韦]），适用于各种无干扰素治疗方案，在低不良反应的情况下，实现了高治愈率（SVR>95%）。在欧洲，它已获得欧洲药品管理局批准，与奥比他韦、帕立瑞韦和利托那韦联合使用，或与利巴韦林联合使用。该药物在初治和既往治疗的患者中均有较高的成功率。它也被批准用于代偿性肝硬化、HIV 合并感染和肝移植受者，这些患者过去曾被排除在干扰素治疗之外。达沙布韦在大型临床试验中进行了广泛评估，与其他口服 DAA 联合使用时，在 HCV 基因型 1 患者中显示出良好的 SVR，安全性和耐受性良好。其缺点是基因型限制、1a 基因型需要利巴韦林（RBV）、耐药屏障低和成本高。它的耐受性良好，不到 1%的患者永久停药，2%的患者出现严重不良反应。已知对利托那韦（如史蒂文斯-约翰逊综合征）过敏和强 CYP3A 和 CYP2CB 诱导剂的患者禁用。
