Lee J H, von Wagner M, Roth W K, Teuber G, Sarrazin C, Zeuzem S
Medizinische Klinik II, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt a.M., Germany.
J Hepatol. 1998 Jul;29(1):29-35. doi: 10.1016/s0168-8278(98)80175-x.
BACKGROUND/AIMS: The combination of ribavirin and interferon alfa has potent synergistic effects in the treatment of chronic hepatitis C. The antiviral mechanism of ribavirin is unknown. We investigated whether a transient initial antiviral effect of ribavirin was sufficient to improve the response to interferon.
Fifteen HCV-infected patients (ten male, five female; mean age 45.4+/-11.0 years) treated with ribavirin (1000-1200 mg) and 17 untreated patients with chronic hepatitis C (11 male, six female; mean age 45.6+/-9.9 years) were investigated. All patients were either non-responders to (n=19) or relapsed after (n=13) previous interferon treatment. Serum HCV-RNA concentrations and HCV quasispecies distribution were serially measured over 4 weeks by quantitative reverse transcription-polymerase chain reaction and single-strand conformation polymorphism analysis, respectively.
In six of the 15 patients treated with ribavirin, but in none of the controls, serum alanine aminotransferase levels declined by at least 30%. Pretreatment HCV-RNA levels ranged from 5.0x10(5)-5.0x10(7) copies/ml. After initiation of ribavirin treatment, minor (0.5-1.0 log) or no changes (<0.5 log) in total hepatitis C viremia were observed in ten and five patients, respectively. In HCV-infected patients without treatment 7/17 patients had minor and 10/17 no changes in viremia. Polymerase chain reaction amplification of the hypervariable region-1 of HCV was successful in 13/15 treated and in 17/17 untreated patients. Changes in HCV quasispecies according to the single-strand conformation polymorphism band pattern occurred in only one patient treated with ribavirin and in three of the untreated patients.
Ribavirin monotherapy has no initial antiviral effect on total hepatitis C viremia nor on HCV quasispecies. Unlike the rapid emergence of antiviral drug-resistant strains in HIV-infected patients, no viral escape phenomena are observed in HCV-infected patients treated with ribavirin.
背景/目的：利巴韦林与干扰素α联合应用在慢性丙型肝炎治疗中具有强大的协同作用。利巴韦林的抗病毒机制尚不清楚。我们研究了利巴韦林短暂的初始抗病毒作用是否足以改善对干扰素的反应。
对15例接受利巴韦林（1000 - 1200mg）治疗的丙型肝炎病毒（HCV）感染患者（10例男性，5例女性；平均年龄45.4±11.0岁）和17例未经治疗的慢性丙型肝炎患者（11例男性，6例女性；平均年龄45.6±9.9岁）进行了研究。所有患者既往对干扰素治疗均无反应（19例）或治疗后复发（13例）。分别通过定量逆转录 - 聚合酶链反应和单链构象多态性分析在4周内连续检测血清HCV - RNA浓度和HCV准种分布。
在15例接受利巴韦林治疗的患者中，有6例血清丙氨酸氨基转移酶水平至少下降了30%，而对照组中无一例下降。治疗前HCV - RNA水平范围为5.0×10⁵ - 5.0×10⁷拷贝/ml。开始利巴韦林治疗后，10例患者的丙型肝炎病毒血症总体有轻微（0.5 - log）变化，5例患者无变化。在未经治疗的HCV感染患者中，17例中有7例病毒血症有轻微变化，10例无变化。对15例接受治疗患者中的13例以及17例未经治疗患者中的17例成功进行了HCV高变区 - 1的聚合酶链反应扩增。根据单链构象多态性条带模式，仅1例接受利巴韦林治疗的患者以及3例未经治疗的患者中出现了HCV准种变化。
利巴韦林单药治疗对丙型肝炎病毒血症总体及HCV准种均无初始抗病毒作用。与HIV感染患者中抗病毒耐药株迅速出现不同，接受利巴韦林治疗的HCV感染患者未观察到病毒逃逸现象。
