Rosen Hugo R, Ribeiro Ruy R, Weinberger Leor, Wolf Stephanie, Chung Minjun, Gretch David R, Perelson Alan S
Division of Gastroenterology and Hepatology, Portland Veterans Affairs Medical Center, Portland, OR 97207, USA.
J Hepatol. 2002 Jul;37(1):124-30. doi: 10.1016/s0168-8278(02)00114-9.
BACKGROUND/AIMS: The majority of patients with genotype 1 do not respond to interferon (IFN) plus ribavirin. Limited data exist on the use of induction followed by combination therapy.
In this prospective study of 28 patients infected with genotype 1, randomization involved either daily or twice daily high dose IFN for 6 weeks, followed by standard therapy of 3 million units three times a week in combination with ribavirin for an additional 42 weeks. Hepatitis C virus (HCV) RNA was quantitated before and frequently during treatment.
The best correlate of response was delta (the infected cell loss rate). Sixteen patients continued on the study because they had at least a 2 log drop in their HCV RNA levels by week 12; all but one were PCR negative for HCV RNA at 48 weeks, and 14 of these 16 patients continued to be PCR negative at 72 weeks. Both African-Americans in our trial failed to respond to therapy, and differences were evident during the induction phase.
This randomized study of induction IFN therapy followed by combination IFN plus ribavirin yielded the highest rate of sustained response (50%) reported to date in chronically HCV-infected patients with genotype 1. The predictive value of the infected cell loss rate needs to be evaluated prospectively in larger studies, particularly in patients receiving pegylated IFN.
背景/目的：大多数基因1型患者对干扰素（IFN）联合利巴韦林治疗无反应。关于采用诱导治疗后再进行联合治疗的数据有限。
在这项针对28例基因1型感染患者的前瞻性研究中，随机分组为每日或每日两次给予高剂量IFN，持续6周，随后采用标准治疗方案，即每周三次给予300万单位IFN联合利巴韦林，再持续治疗42周。在治疗前及治疗期间频繁对丙型肝炎病毒（HCV）RNA进行定量检测。
反应的最佳关联指标是delta（感染细胞损失率）。16例患者继续参与研究，因为到第12周时他们的HCV RNA水平至少下降了2个对数；48周时，这16例患者中除1例之外均HCV RNA PCR检测呈阴性，其中14例患者在72周时仍为PCR阴性。我们试验中的两名非裔美国人治疗无反应，且在诱导期差异明显。
这项关于诱导IFN治疗后联合IFN加利巴韦林的随机研究，在慢性基因1型HCV感染患者中取得了迄今为止报道的最高持续反应率（50%）。感染细胞损失率的预测价值需要在更大规模的研究中进行前瞻性评估，尤其是在接受聚乙二醇化IFN治疗的患者中。
