Tsubota Akihito, Arase Yasuji, Suzuki Fumitaka, Suzuki Yoshiyuki, Akuta Norio, Hosaka Tetsuya, Someya Takashi, Kobayashi Masahiro, Saitoh Satoshi, Ikeda Kenji, Kumada Hiromitsu
Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan.
J Gastroenterol. 2004;39(2):155-61. doi: 10.1007/s00535-003-1266-9.
Although pegylated interferon (IFN) is now used in many countries as a standard therapy for chronic hepatitis C, the efficacy and safety of combination therapy of high-dose interferon alpha-2b induction with ribavirin are not fully evaluated, especially in Japanese patients infected with hepatitis C virus (HCV) genotype 1b with a high viral load.
Patients ( n = 83) received daily, high-dose induction therapy of interferon alpha-2b (6 million units [MU] once daily for 2 weeks), followed by 6 MU three times weekly for 22 weeks. Oral ribavirin (800 or 600 mg/day) was given daily for 24 weeks, and then the patients were followed up for 24 weeks.
Of the 83 patients, 67 (81%) had a biochemical response (BR), and 37 (45%) achieved a sustained BR (SBR). Virologic response (VR; undetectable serum HCV RNA level by polymerase chain reaction [PCR]) was noted in 55 (66%) patients, and sustained VR (SVR) in 16 (19%) patients. Baseline viral load did not influence treatment outcome. There was no significant difference in treatment outcome among treatment-naIve patients, relapsers, and nonresponders to previous IFN monotherapy. Multivariate analyses identified serum ribavirin concentrations at week 8 of therapy (odds ratio [OR], 23.7; 95% confidence interval [CI], 1.84-61.1; P = 0.015) and negativity for serum HCV RNA at week 8 (OR, 22.5; CI, 1.76-57.5; P = 0.017, respectively) as two significant and independent predictors of SVR.
The efficacy of 24-week combination therapy of high-dose IFN alpha-2b induction and ribavirin deserves attention in HCV genotype 1b patients with a high viral load, especially in nonresponders to previous IFN monotherapy and patients with a very high viral load.
尽管聚乙二醇化干扰素（IFN）目前在许多国家被用作慢性丙型肝炎的标准治疗方法，但高剂量干扰素α-2b诱导联合利巴韦林的联合治疗的疗效和安全性尚未得到充分评估，尤其是在感染丙型肝炎病毒（HCV）基因1b型且病毒载量高的日本患者中。
患者（n = 83）接受每日高剂量干扰素α-2b诱导治疗（600万单位[MU]，每日一次，共2周），随后每周三次，每次6 MU，共22周。口服利巴韦林（800或600 mg/天），每日给药24周，然后对患者进行24周的随访。
83例患者中，67例（81%）有生化反应（BR），37例（45%）实现持续生化反应（SBR）。55例（66%）患者有病毒学反应（VR；聚合酶链反应[PCR]检测血清HCV RNA水平不可测），16例（19%）患者有持续病毒学反应（SVR）。基线病毒载量不影响治疗结果。初治患者、复发患者和既往IFN单药治疗无反应者的治疗结果无显著差异。多变量分析确定治疗第8周时血清利巴韦林浓度（比值比[OR]，23.7；95%置信区间[CI]，1.84 - 61.1；P = 0.015）和第8周时血清HCV RNA阴性（OR，22.5；CI，1.76 - 57.5；P = 0.017）是SVR的两个显著且独立的预测因素。
高剂量IFNα-2b诱导联合利巴韦林的24周联合治疗的疗效值得关注，尤其是在病毒载量高的HCV基因1b型患者中，特别是既往IFN单药治疗无反应者和病毒载量非常高的患者。
