Hepatology Laboratory, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
PLoS One. 2010 Nov 8;5(11):e15492. doi: 10.1371/journal.pone.0015492.
BACKGROUND/AIMS: Treatment of chronic hepatitis C (CHC) with pegylated interferon α (pegIFNα) and ribavirin results in a sustained response in approximately half of patients. Viral interference with IFNα signal transduction through the Jak-STAT pathway might be an important factor underlying treatment failure. S-adenosyl-L-methionine (SAMe) and betaine potentiate IFNα signaling in cultured cells that express hepatitis C virus (HCV) proteins, and enhance the inhibitory effect of IFNα on HCV replicons. We have performed a clinical study with the aim to evaluate efficacy and safety of the addition of SAMe and betaine to treatment of CHC with pegIFNα/ribavirin.
In this open-label pilot study, 29 patients with CHC who failed previous therapy with (peg)IFNα/ribavirin were treated with SAMe, betaine, pegIFNα2b and ribavirin. Treatment duration was 6 or 12 months, depending on genotype, and the protocol comprised a stopping rule at week 12 if early virological response (EVR) was not achieved. Virological and biochemical response and safety were assessed throughout the treatment.
29 patients were enrolled and treated according to the study protocol. 79% of the patients were infected with genotype 1, 72% had advanced fibrosis, 76% had previously received pegIFNα/ribavirin, and only 14% achieved EVR to the previous treatment. When treated with the study medications, 17 patients (59%) showed an EVR, only 3 (10%) however achieved a sustained virological response (SVR). SAMe and betaine were found to be safe when used with pegIFNα/ribavirin.
The addition of SAMe and betaine to pegIFNα/ribavirin improves early virological response in CHC.
ClinicalTrials.gov NCT00310336.
背景/目的：聚乙二醇干扰素α（pegIFNα）和利巴韦林治疗慢性丙型肝炎（CHC）可使大约一半的患者获得持续应答。病毒通过 Jak-STAT 途径干扰 IFNα 信号转导可能是治疗失败的一个重要因素。S-腺苷-L-蛋氨酸（SAMe）和甜菜碱可增强表达丙型肝炎病毒（HCV）蛋白的培养细胞中 IFNα 的信号转导，并增强 IFNα 对 HCV 复制子的抑制作用。我们进行了一项临床研究，旨在评估 SAMe 和甜菜碱联合聚乙二醇干扰素α/利巴韦林治疗 CHC 的疗效和安全性。
在这项开放标签的初步研究中，29 例先前接受（peg）IFNα/利巴韦林治疗失败的 CHC 患者接受 SAMe、甜菜碱、pegIFNα2b 和利巴韦林治疗。治疗持续时间取决于基因型，为 6 或 12 个月，如果未达到早期病毒学应答（EVR），则在第 12 周按方案停药。整个治疗过程中评估病毒学和生化应答以及安全性。
29 例患者按研究方案入组并接受治疗。79%的患者感染基因型 1，72%有晚期纤维化，76%曾接受 pegIFNα/利巴韦林治疗，仅有 14%对先前治疗有 EVR。用研究药物治疗时，17 例（59%）患者有 EVR，但仅 3 例（10%）患者获得持续病毒学应答（SVR）。SAMe 和甜菜碱与 pegIFNα/利巴韦林联合使用时被发现是安全的。
SAMe 和甜菜碱联合 pegIFNα/利巴韦林可提高 CHC 的早期病毒学应答。
ClinicalTrials.gov NCT00310336。
