长效干扰素治疗对丙型肝炎病毒1b型、高病毒载量的慢性丙型肝炎患者的疗效。

Efficacy of prolonged interferon therapy for patients with chronic hepatitis C with HCV-genotype 1b and high virus load.

作者信息

Arase Yasuji, Ikeda Kenji, Tsubota Akihito, Suzuki Yoshiyuki, Saitoh Satoshi, Kobayashi Masahiro, Kobayashi Mariko, Suzuki Fumitaka, Akuta Norio, Someya Takashi, Kumada Hiromitsu

机构信息

Department of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo 105-8470, Japan.

出版信息

J Gastroenterol. 2003;38(2):158-63. doi: 10.1007/s005350300026.

DOI:10.1007/s005350300026

PMID:12640530

Abstract

BACKGROUND

In patients with hepatitis C virus (HCV)-genotype 1b and a high virus load, of more than 1 Meq/ml by the DNA probe assay, the clearance of HCV-RNA was achieved in only 10% with a 6-month interferon (IFN) course. We therefore assessed the efficacy of prolonged IFN therapy in patients with HCV-genotype 1b and a high virus load.

METHODS

A total of 51 patients with HCV genotype 1b who were given 6 million units (MU) of natural IFN-alpha daily for 8 weeks followed by three-times-weekly treatment with natural IFN-alpha for 16 weeks, were enrolled in this trial. These 51 patients were randomly assigned to one of two schedule groups at the time of termination of the first IFN therapy. The 48-week-group patients (n = 25) were given 6 MU of natural IFN-alpha by intramuscular injection three times weekly for 24 weeks, beginning within a week after the termination of the first IFN therapy. The 72-week-group patients (n = 26) were given 6 MU of IFN-alpha by intramuscular injection three times a week for 48 weeks, beginning within a week after the termination of the first IFN therapy. The therapeutic efficacy was evaluated 24 and 30 months after the initiation of the first IFN treatment. A virological response (VR) to IFN therapy was defined as the normalization of serum alanime amino transferase (ALT) level (ALT less, similar 50 IU) and HCV-RNA negativity at the two time points. Biochemical response (BR) was defined as the normalization of serum ALT, but positivity for HCV-RNA, assessed by commercial Amplicor HCV qualitative assays, at the two time points.

RESULTS

The efficacy of IFN treatment was assessed in relation to the IFN administration schedule by intention-to-treat (ITT) analysis and per-protocol analysis. With respect to the IFN regimen, VR occurred in 16.6% (4/24) of the patients in the 48-week-group with additional IFN and in 20% (5/25) in the 72-week-group with additional IFN by ITT analysis. The BR rate was 33.3% (8/24) in the 48-week group and 48% (12/25) in the 72-week group.

CONCLUSIONS

We found that prolonged IFN therapy could be a worthwhile treatment strategy for patients with HCV genotype 1b and a high serum virus load.

摘要

背景

在丙型肝炎病毒（HCV）1b基因型且病毒载量高（通过DNA探针检测法大于1 Meq/ml）的患者中，采用6个月的干扰素（IFN）疗程，仅10%的患者实现了HCV-RNA清除。因此，我们评估了延长IFN治疗对HCV 1b基因型且病毒载量高的患者的疗效。

方法

本试验纳入了51例HCV 1b基因型患者，他们先每日接受600万单位（MU）天然α干扰素治疗8周，随后每周三次接受天然α干扰素治疗16周。在首次IFN治疗结束时，这51例患者被随机分配到两个疗程组之一。48周疗程组患者（n = 25）在首次IFN治疗结束后一周内开始，每周三次肌肉注射6 MU天然α干扰素，共24周。72周疗程组患者（n = 26）在首次IFN治疗结束后一周内开始，每周三次肌肉注射6 MU干扰素α，共48周。在首次IFN治疗开始后24个月和30个月评估治疗效果。IFN治疗的病毒学应答（VR）定义为两个时间点血清丙氨酸氨基转移酶（ALT）水平正常化（ALT小于或等于50 IU）且HCV-RNA阴性。生化应答（BR）定义为两个时间点血清ALT正常化，但通过商业Amplicor HCV定性检测法评估HCV-RNA为阳性。

结果

通过意向性分析（ITT）和符合方案分析评估了IFN治疗效果与IFN给药方案的关系。关于IFN治疗方案，通过ITT分析，48周疗程组接受额外IFN治疗的患者中VR发生率为16.6%（4/24），72周疗程组接受额外IFN治疗的患者中VR发生率为20%（5/25）。48周疗程组的BR率为33.3%（8/24），72周疗程组为48%（12/25）。