National Liver Institute, Menoufiya, Egypt.
Egyptian Liver Research Institute And Hospital (ELRIAH), Dakahliah, Egypt.
Lancet Gastroenterol Hepatol. 2016 Sep;1(1):36-44. doi: 10.1016/S2468-1253(16)30002-4. Epub 2016 Jun 16.
In Egypt, chronic hepatitis C virus (HCV) infection occurs in around 10% of the population (about 8 million individuals), and is a leading cause of liver cirrhosis, hepatocellular carcinoma, and mortality. Although HCV genotype 4 constitutes about 20% of HCV infections worldwide, the prevalence in Egypt is more than 90%. We assessed the efficacy and safety of the two direct-acting antiviral drugs ombitasvir, an NS5A inhibitor, and paritaprevir, an NS3/4A protease inhibitor dosed with ritonavir, plus ribavirin in treatment of chronic HCV infection in Egypt.
AGATE-II was a phase 3, open-label, partly randomised trial in patients with chronic HCV genotype 4 infection recruited from five academic and hepatology centres in Egypt. Patients were HCV treatment-naive or treatment-experienced with interferon-based regimens. Eligible patients were aged 18 years or older, and had been chronically infected with HCV genotype 4 for at least 6 months with a plasma HCV RNA concentration of more than 1000 IU/mL at screening. Patients without cirrhosis were assigned to receive 12 weeks of 25 mg ombitasvir, 150 mg paritaprevir, and 100 mg ritonavir orally once daily plus weight-based ribavirin. Patients with compensated cirrhosis were randomly assigned (1:1) to receive the same treatment for either 12 weeks or 24 weeks. Randomisation was stratified by previous pegylated interferon and ribavirin treatment experience using a web-based interactive response technology system and computer-generated schedules prepared by personnel from the funder's statistics department. Investigators were masked to randomisation schedules and were informed of each patient's assigned treatment by the interactive response technology system immediately after allocation. The primary endpoint was the proportion of patients with a sustained virological response (HCV RNA <15 IU/mL) 12 weeks after the last dose of study drug (SVR12). All patients who received at least one dose of study drugs were included in the primary and safety analysis. This study is registered with ClinicalTrials.gov, number NCT02247401.
Between Nov 4, 2014, and March 16, 2015, we screened 182 patients with HCV infection, of whom 160 were eligible for inclusion; 100 patients were assessed as not having cirrhosis and were given 12 weeks of treatment, and 60 patients assessed as having cirrhosis were randomly assigned to the 12-week treatment group (n=31) or the 24-week treatment group (n=29). 94 (94%; 95% CI 88-97) of 100 patients in the without cirrhosis group, 30 (97%; 84-99) of 31 patients in the cirrhosis 12-week treatment group, and 27 (93%; 78-98) of 29 patients in the cirrhosis 24-week treatment group achieved SVR12. The most common adverse events in patients without cirrhosis were headache (41 [41%]) and fatigue (35 [35%]). Fatigue occurred in nine (29%) patients in the cirrhosis 12-week treatment group and 11 (38%) patients in the cirrhosis 24-week treatment group, and headache occurred in nine (29%) patients in the cirrhosis 12-week treatment group and in 10 (35%) patients in the cirrhosis 24-week treatment group. Adverse events were predominantly mild or moderate in severity, and laboratory abnormalities were not clinically meaningful. No patients discontinued treatment because of an adverse event. One serious adverse event in the group without cirrhosis was attributed to study drugs by the investigators; the patient had deep venous thrombosis.
Ombitasvir, paritaprevir, and ritonavir plus ribavirin for 12 weeks achieved SVR12 in a high proportion of patients and was well tolerated in Egyptian patients with HCV genotype 4 infection with or without compensated cirrhosis. Extension of treatment to 24 weeks in patients with cirrhosis did not improve the proportion of patients achieving SVR12. A shorter duration regimen could be useful to address the significant burden of HCV genotype 4 infection in patients with compensated cirrhosis.
AbbVie.
在埃及，慢性丙型肝炎病毒（HCV）感染发生率约为 10%（约 800 万人），是导致肝硬化、肝细胞癌和死亡的主要原因。尽管 HCV 基因型 4 约占全球 HCV 感染的 20%，但埃及的流行率超过 90%。我们评估了两种直接作用抗病毒药物 ombitasvir（一种 NS5A 抑制剂）和 paritaprevir（一种 NS3/4A 蛋白酶抑制剂，与利托那韦联合使用）加利巴韦林在埃及治疗慢性 HCV 感染的疗效和安全性。
AGATE-II 是一项在埃及五个学术和肝脏中心招募的慢性 HCV 基因型 4 感染患者中进行的 3 期、开放性、部分随机试验。患者为 HCV 初治或基于干扰素的方案治疗失败的患者。合格的患者年龄为 18 岁或以上，在筛选时有至少 6 个月的慢性 HCV 基因型 4 感染，且血浆 HCV RNA 浓度大于 1000 IU/mL。无肝硬化的患者被分配接受 12 周的 25mg ombitasvir、150mg paritaprevir 和 100mg 利托那韦每日口服一次，加基于体重的利巴韦林。有代偿性肝硬化的患者随机（1:1）接受相同的治疗 12 周或 24 周。根据以前的聚乙二醇干扰素和利巴韦林治疗经验进行分层，使用基于网络的交互式反应技术系统和由资助者统计部门的工作人员准备的计算机生成的方案。研究者对随机分组方案不了解，并且在分配后立即通过交互式反应技术系统了解每个患者的指定治疗。主要终点是最后一剂研究药物后 12 周持续病毒学应答（HCV RNA <15IU/mL）的比例（SVR12）。所有接受至少一剂研究药物的患者均纳入主要和安全性分析。本研究在 ClinicalTrials.gov 注册，编号为 NCT02247401。
在 2014 年 11 月 4 日至 2015 年 3 月 16 日期间，我们筛选了 182 例 HCV 感染患者，其中 160 例符合纳入标准；100 例患者评估为无肝硬化，接受 12 周治疗，60 例评估为肝硬化的患者随机分为 12 周治疗组（n=31）或 24 周治疗组（n=29）。无肝硬化组的 100 例患者中，94 例（94%；95%CI 88-97），肝硬化 12 周治疗组的 31 例患者中，30 例（97%；84-99），肝硬化 24 周治疗组的 29 例患者中，27 例（93%；78-98）达到 SVR12。无肝硬化患者最常见的不良反应是头痛（41[41%]）和疲劳（35[35%]）。肝硬化 12 周治疗组 9 例（29%）和肝硬化 24 周治疗组 11 例（38%）患者发生疲劳，肝硬化 12 周治疗组 9 例（29%）和肝硬化 24 周治疗组 10 例（35%）患者发生头痛。不良反应主要为轻度或中度，实验室异常无临床意义。没有患者因不良反应而停止治疗。无肝硬化组的 1 例严重不良事件被研究者归因于研究药物；患者患有深静脉血栓形成。
在埃及有代偿性肝硬化的 HCV 基因型 4 感染患者中，ombitasvir、paritaprevir 和利托那韦加利巴韦林治疗 12 周可获得较高的 SVR12 比例，且耐受性良好。在肝硬化患者中延长治疗至 24 周并未提高 SVR12 的比例。对于有代偿性肝硬化的患者，较短的治疗方案可能有助于解决 HCV 基因型 4 感染的巨大负担。
艾伯维。
