Abdel-Aziz Asmaa M, Ibrahim Mohamed A, El-Sheikh Azza A, Kamel Maha Y, Zenhom Nagwa M, Abdel-Raheim Salam, Abdelhaleem Hisham
Department of Pharmacology, Faculty of Medicine, Minia University, 61511 Minia, Egypt.
Basic Health Sciences Department, Faculty of Medicine, Princess Nourah Bint Abdulrahman University, 11671 Riyadh, Saudi Arabia.
J Clin Exp Hepatol. 2018 Mar;8(1):15-22. doi: 10.1016/j.jceh.2017.06.006. Epub 2017 Jun 30.
BACKGROUND/PURPOSE: The effect of sofosbuvir and daclatasvir in treatment of genotype 4 Hepatitis C Virus (HCV) is not well documented. This study investigated the safety and efficacy of sofosbuvir plus daclatasvir with or without ribavirin in treatment of HCV genotype 4 patients. The impact of therapy on liver fibrosis as well as the role of IL18 polymorphism in therapeutic outcome was assessed.
One hundred HCV genotype 4 patients were categorized into 2 groups. The group 1 comprised treatment naïve patients, with total serum bilirubin ≤ 1.2 mg/10 L, serum albumin ≥ 3.5 g/10 L, INR ≤ 1.2, and platelet count ≥ 150 × 10/L. This group was treated with sofosbuvir plus daclatasvir for 12 weeks. The group 2 included Peg-IFN-α-or sofosbuvir treatment experienced, or patients with at least 2 of the following findings: total serum bilirubin > 1.2 mg/10 L, serum albumin < 3.5 g/10 L, INR > 1.2, and platelet count < 150 × 10L. Group 2 was treated with sofosbuvir-daclatasvir + ribavirin for 12 weeks, with the exception of sofosbuvir treatment experienced patients, who were treated with sofosbuvir/daclatasvir + ribavirin for 24 weeks.
Sustained Virological Response (SVR12) (undetectable viremia12 weeks post-treatment), was 93.3% in group 1 and 87.5% in group 2 (total = 91%). Such high efficacy was accompanied with tolerable adverse effects as well as with significant improvement in liver fibrosis. No significant association was observed between IL18 polymorphism (rs1946518) at position -607 and achievement of SVR12 in HCV patients after treatment.
Sofosbuvir plus daclatasvir, with or without ribavirin achieved high efficacy and safety in HCV genotype 4 patients. Their effects were accompanied with attenuation of liver fibrosis. Further wider-scale studies are needed to evaluate the actual role of IL18 polymorphisms in treatment response with sofosbuvir/daclatasvir.
背景/目的：索磷布韦和达卡他韦治疗4型丙型肝炎病毒（HCV）的效果尚无充分文献记载。本研究调查了索磷布韦联合达卡他韦加或不加利巴韦林治疗HCV 4型患者的安全性和疗效。评估了治疗对肝纤维化的影响以及IL18基因多态性在治疗结果中的作用。
100例HCV 4型患者分为2组。第1组为初治患者，总血清胆红素≤1.2mg/10L，血清白蛋白≥3.5g/10L，国际标准化比值（INR）≤1.2，血小板计数≥150×10⁹/L。该组接受索磷布韦联合达卡他韦治疗12周。第2组包括接受过聚乙二醇干扰素-α或索磷布韦治疗的患者，或至少有以下2项表现的患者：总血清胆红素>1.2mg/10L，血清白蛋白<3.5g/10L，INR>1.2，血小板计数<150×10⁹/L。第2组接受索磷布韦-达卡他韦+利巴韦林治疗12周，但接受过索磷布韦治疗的患者接受索磷布韦/达卡他韦+利巴韦林治疗24周。
持续病毒学应答（SVR12）（治疗后12周病毒血症检测不到）在第1组为93.3%，在第2组为87.5%（总体=91%）。如此高的疗效伴随着可耐受的不良反应以及肝纤维化的显著改善。治疗后，HCV患者中-607位的IL18基因多态性（rs1946518）与实现SVR12之间未观察到显著关联。
索磷布韦联合达卡他韦，加或不加利巴韦林，在HCV 4型患者中均实现了高疗效和安全性。它们的作用伴随着肝纤维化的减轻。需要进一步开展更广泛的研究来评估IL18基因多态性在索磷布韦/达卡他韦治疗反应中的实际作用。
