Department of Hepatology, Toranomom Hospital, Kawasaki City, Japan.
Hepatol Res. 2009 Nov;39(11):1056-63. doi: 10.1111/j.1872-034X.2009.00548.x. Epub 2009 Jul 10.
To evaluate the efficacy and safety of the triple treatment with telaprevir (MP-424), pegylated interferon (PEG-IFN) and ribavirin during 12 weeks on-treatment.
The triple treatment was given to 20 patients with chronic hepatitis C who had been infected with hepatitis C virus (HCV)-1b in high viral load (median: 6.8 log IU/mL [range: 5.5-7.2]), with a median age of 54 years (range: 36-65 years). They were followed for early dynamics of HCV RNA in serum during 12 weeks and side-effects.
HCV RNA levels decreased by 4.8 logs by 7 days and 5.5 logs by 14 days. HCV RNA disappeared in 50% (10/20) at 2 weeks, 79% (15/19) at 4 weeks, 88% (14/16) at 6 weeks, 94% (15/16) at 8 weeks and 100% (13/13) at 12 weeks. HCV RNA disappeared equally frequently in 10 treatment-naive patients, six non-responders to IFN monotherapy and four non-responders to PEG-IFN and ribavirin. It was no different in the patients with and without amino acid substitutions reducing the response to IFN. The treatment was withdrawn in seven (35%) patients, mostly due to reduced hemoglobin of less than 8.5 g/dL, of whom six (86%) remained clear of HCV RNA at 12 weeks.
HCV RNA was lost from serum rapidly and universally in patients infected with HCV-1b in high viral loads by the triple treatment. Because an early loss of HCV RNA correlates with high rates of sustained virological response (SVR), it would increase SVR substantially, and merit the patients who have not responded to previous therapies.
评估替拉瑞韦(MP-424)、聚乙二醇干扰素(PEG-IFN)和利巴韦林三联治疗 12 周的疗效和安全性。
对 20 例感染高病毒载量(中位数:6.8logIU/mL[范围:5.5-7.2])丙型肝炎病毒(HCV)-1b 的慢性丙型肝炎患者给予三联治疗,中位年龄 54 岁(范围:36-65 岁)。随访 12 周血清 HCV RNA 的早期动态变化及不良反应。
HCV RNA 水平在第 7 天下降 4.8 个对数级,第 14 天下降 5.5 个对数级。第 2 周时 HCV RNA 消失率为 50%(10/20),第 4 周时为 79%(15/19),第 6 周时为 88%(14/16),第 8 周时为 94%(15/16),第 12 周时为 100%(13/13)。10 例初治患者、6 例 IFN 单药治疗无应答者和 4 例 PEG-IFN 和利巴韦林无应答者的 HCV RNA 消失频率相同。对 IFN 应答率降低的氨基酸替代患者与无替代患者之间无差异。有 7 例(35%)患者停药,主要原因是血红蛋白降低至<8.5g/dL,其中 6 例(86%)在 12 周时仍未检出 HCV RNA。
高病毒载量 HCV-1b 感染患者经三联治疗后,血清 HCV RNA 迅速且普遍消失。由于 HCV RNA 早期丢失与高持续病毒学应答(SVR)率相关,因此会显著提高 SVR,值得既往治疗无应答的患者尝试。