Saibara Toshiji, Enomoto Nobuyuki, Kaneko Shuichi, Chayama Kazuaki, Sata Michio, Imawari Michio, Onishi Saburo, Okita Kiwamu
Department of Gastroenterology and Hepatology, Kochi Medical School, Nankoku, Japan.
First Department of Internal Medicine, Facility of Medicine, University of Yamanashi, Chuou-shi, Japan.
Hepatol Res. 2014 Apr;44(4):410-9. doi: 10.1111/hepr.12139. Epub 2013 Jun 20.
ME3738, a derivative of soyasapogenol B, enhances the anti-hepatitis C virus (HCV) effect of interferon in an in vitro replication system and an in vivo mouse model of HCV infection. ME3738 plus pegylated interferon (PEG IFN)-α-2a treatment for 12 weeks decreased HCV RNA levels in enrolled late virus responder (LVR) patients with relapsed HCV. Half of the patients reached undetectable HCV RNA level. The present clinical study of ME3738 was conducted in naïve chronic hepatitis C patients to investigate the sustained virological response (SVR) and safety of 48-week treatment with ME3738 plus PEG IFN-α-2a.
Subjects (n = 135) with genotype 1b chronic hepatitis C with high viral loads were divided into three groups (ME3738 50 mg b.i.d., 200 mg b.i.d. or 800 mg b.i.d.). ME3738 was administrated p.o. and PEG IFN-α-2a (180 μg/week) s.c. for 48 weeks, and SVR was assessed at 24 weeks of treatment-free follow up.
The viral disappearance rates at 12 and 48 weeks were 23.0% and 48.9%, respectively. SVR was seen in 5.9% of subjects. ME3738 did not worsen the adverse reactions generally seen with PEG IFN-α-2a treatment, and any adverse reactions specific to ME3738 were not observed.
ME3738 plus PEG IFN-α-2a treatment to naïve chronic hepatitis C patients showed an antiviral effect and a good safety profile up to 48 weeks. However, HCV RNA was again detected in many subjects after treatment termination. Even though ME3738 is not enough to suppress HCV reproduction in this treatment. ME3738 was concurrently used with PEG IFN-α-2a treatment; however, a clear additional effect on SVR was not confirmed.
ME3738是大豆皂醇B的衍生物，在体外复制系统和丙型肝炎病毒（HCV）感染的体内小鼠模型中可增强干扰素的抗HCV作用。ME3738联合聚乙二醇化干扰素（PEG IFN）-α-2a治疗12周可降低入组的复发HCV的晚期病毒应答者（LVR）患者的HCV RNA水平。半数患者的HCV RNA水平降至检测不到。本项关于ME3738的临床研究在初治慢性丙型肝炎患者中进行，以调查ME3738联合PEG IFN-α-2a治疗48周的持续病毒学应答（SVR）及安全性。
将135例高病毒载量的1b型慢性丙型肝炎患者分为三组（ME3738 50 mg每日两次、200 mg每日两次或800 mg每日两次）。口服ME3738，皮下注射PEG IFN-α-2a（180 μg/周），共48周，并在停药随访24周时评估SVR。
12周和48周时的病毒清除率分别为23.0%和48.9%。5.9%的受试者出现SVR。ME3738未加重PEG IFN-α-2a治疗常见的不良反应，且未观察到ME3738特有的不良反应。
初治慢性丙型肝炎患者接受ME3738联合PEG IFN-α-2a治疗48周显示出抗病毒作用且安全性良好。然而，治疗终止后许多受试者的HCV RNA再次被检测到。尽管在此治疗中ME3738不足以抑制HCV复制。ME3738与PEG IFN-α-2a联合使用；然而，未证实对SVR有明显的附加作用。
