Shiratori Y, Yokosuka O, Nakata R, Ihori M, Hirota K, Katamoto T, Unuma T, Okano K, Ikeda Y, Hirano M, Kawase T, Takano S, Matsumoto K, Ohashi Y, Omata M
Department of Internal Medicine (II), University of Tokyo, Tokyo, Japan.
Hepatology. 1999 May;29(5):1573-80. doi: 10.1002/hep.510290529.
Because interferon therapy exhibits low efficacy for cirrhotic patients infected with hepatitis C virus, this prospective study was conducted to determine effective interferon regimens tailored to treatment response by monitoring HCV RNA status. A total of 157 cirrhotic patients were enrolled to receive 9 million units (MU) of interferon three times a week. The HCV RNA values were drawn 8 weeks apart and the patients were randomized to a further 16 or 32 weeks of treatment after two sequential findings of negativity for HCV RNA. A total of 73 out of 157 patients (46%) proceeded to randomization to different durations of treatment, 37 short-course and 36 long-course (duration: 38 +/- 8 and 49 +/- 13 weeks; total amount of interferon: 940 +/- 240 and 1130 +/- 390 MU, respectively). The remaining 84 patients without two sequential negative serum HCV RNA determinations received 44.8 +/- 27.4 weeks of interferon (IFN) therapy with total amount of 993 +/- 633 MU. Of these 157 patients, sustained virological and biochemical response was shown in 32 (20%) and 37 patients (24%), respectively. Sustained virological and biochemical response rate in the randomized patients was significantly higher than in nonrandomized patients (41% vs. 2%, and 38% vs. 11%; each P <.01). Of the 73 randomized patients, the rate of sustained virological response in patients with long-course treatment (50%) was significantly higher than that of patients with short-course treatment (32%) (P =.026: log-rank test), and in patients with early disappearance of HCV RNA especially within 8 weeks, in patients with low virus load (</=10(6.3) copies/mL) and with HCV 2a. Multivariate analysis revealed that HCV RNA level and subtypes were the most important factors contributing to sustained virological response. Interferon is effective even in cirrhotic patients with low viral load and HCV 2a, but requires a longer course of administration.
由于干扰素疗法对丙型肝炎病毒感染的肝硬化患者疗效较低，因此开展了这项前瞻性研究，通过监测HCV RNA状态来确定适合治疗反应的有效干扰素治疗方案。共有157例肝硬化患者入选，接受每周三次、每次900万单位（MU）的干扰素治疗。每隔8周检测一次HCV RNA值，在连续两次检测到HCV RNA阴性后，将患者随机分为再接受16周或32周治疗两组。157例患者中共有73例（46%）进入不同疗程的随机分组，37例接受短疗程治疗，36例接受长疗程治疗（疗程分别为：38±8周和49±13周；干扰素总量分别为：940±240 MU和1130±390 MU）。其余84例未连续两次检测到血清HCV RNA阴性的患者接受了44.8±27.4周的干扰素（IFN）治疗，总量为993±633 MU。在这157例患者中，分别有32例（20%）和37例（24%）出现持续病毒学应答和持续生化应答。随机分组患者的持续病毒学应答率和持续生化应答率显著高于未随机分组患者（分别为41%对2%，38%对11%；P均<0.01）。在73例随机分组患者中，长疗程治疗患者的持续病毒学应答率（50%）显著高于短疗程治疗患者（32%）（P = 0.026：对数秩检验），在HCV RNA早期消失尤其是在8周内消失的患者、病毒载量低（≤10⁶.³拷贝/mL）以及感染HCV 2a型的患者中也是如此。多因素分析显示，HCV RNA水平和亚型是导致持续病毒学应答的最重要因素。即使对于病毒载量低且感染HCV 2a型的肝硬化患者，干扰素也是有效的，但需要更长的给药疗程。
