Zeuzem S, Schmidt J M, Lee J H, von Wagner M, Teuber G, Roth W K
Medizinische Klinik II, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt a.M., Germany.
Hepatology. 1998 Jul;28(1):245-52. doi: 10.1002/hep.510280132.
Treatment of patients with chronic hepatitis C with recombinant interferon alfa (rIFN-alpha) can cause a decrease of serum transaminases and hepatitis C virus (HCV) RNA. Recent trials evaluating combination therapy of IFN-alpha and ribavirin suggested a potential synergistic effect. From serial measurements of serum HCV RNA concentrations following treatment-induced perturbation of the balance between virus production and clearance, we compared the antiviral efficacy of both IFN-alpha alone and IFN-alpha in combination with ribavirin. Chronically HCV-infected patients were treated with either 3 x 3 MU or 3 x 6 MU rIFN-alpha per week or 3 x 6 MU rIFN-alpha plus 14 mg/kg of body weight ribavirin per day. The time-dependent HCV RNA concentrations during antiviral treatment were analyzed by iterative least-squares regression. After initiation of antiviral therapy, HCV RNA declined exponentially below the detection limit of the reverse-transcription polymerase chain reaction assay (1,000 HCV RNA molecules per milliliter) in 10 of 26 (39%), 10 of 19 (53%), and 10 of 18 patients (56%) treated with 3 x 3 MU, 3 x 6 MU rIFN-alpha without and with ribavirin, respectively. Viral clearance from serum was faster in patients treated with 3 x 6 MU rIFN-alpha (t1/2 = 0.23 +/- 0.15) compared with patients treated with 3 x 3 MU rIFN-alpha per week (0.67 +/- 0.36 days) (P < .004). However, half-lives of viral clearance were similar in patients treated with rIFN-alpha or rIFN-alpha plus ribavirin. For virus release from infected hepatocytes, absence and presence of ribavirin yielded half-lives of t1/2 = 2.54 +/- 2.10 and t1/2 = 1.99 +/- 1.70, respectively, indicating that ribavirin does not significantly inhibit HCV production. In conclusion, the data of the present study indicate that higher rIFN-alpha doses accelerate viral clearance from serum. Ribavirin (14 mg/kg/d), however, lacks synergistic antiviral effects in the treatment of chronic hepatitis C with 3 x 6 MU rIFN-alpha per week.
用重组干扰素α（rIFN-α）治疗慢性丙型肝炎患者可导致血清转氨酶和丙型肝炎病毒（HCV）RNA水平下降。最近评估IFN-α与利巴韦林联合治疗的试验提示了一种潜在的协同效应。通过对治疗引起的病毒产生与清除平衡扰动后血清HCV RNA浓度的系列测量，我们比较了单独使用IFN-α以及IFN-α与利巴韦林联合使用的抗病毒疗效。慢性HCV感染患者分别接受每周3×3MU或3×6MU的rIFN-α治疗，或每天3×6MU的rIFN-α加14mg/kg体重的利巴韦林治疗。通过迭代最小二乘法回归分析抗病毒治疗期间随时间变化的HCV RNA浓度。抗病毒治疗开始后，在接受3×3MU、3×6MU rIFN-α单药治疗以及联合利巴韦林治疗的患者中，分别有10/26（39%）、10/ of 19（53%）和10/18患者（56%）的HCV RNA呈指数下降至逆转录聚合酶链反应检测限（每毫升1000个HCV RNA分子）以下。与每周接受3×3MU rIFN-α治疗的患者（t1/2 = 0.67 +/- 0.36天）相比，接受3×6MU rIFN-α治疗的患者血清病毒清除更快（t1/2 = 0.23 +/- 0.15）（P <.004）。然而，接受rIFN-α或rIFN-α加利巴韦林治疗的患者病毒清除半衰期相似。对于病毒从受感染肝细胞的释放，不存在和存在利巴韦林时的半衰期分别为t1/2 = 2.54 +/- 2.10和t1/2 = 1.99 +/- 1.70，表明利巴韦林不会显著抑制HCV的产生。总之，本研究数据表明，较高剂量的rIFN-α可加速血清病毒清除。然而，利巴韦林（14mg/kg/d）在每周3×6MU rIFN-α治疗慢性丙型肝炎时缺乏协同抗病毒作用。
