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血友病患者慢性丙型肝炎感染的干扰素治疗——病毒载量、基因型和肝脏病理对疗效的影响

Interferon treatment for chronic hepatitis C infection in hemophiliacs--influence of virus load, genotype, and liver pathology on response.

作者信息

Hanley J P, Jarvis L M, Andrew J, Dennis R, Hayes P C, Piris J, Lee R, Simmonds P, Ludlam C A

机构信息

Department of Haematology, Royal Infirmary of Edinburgh, Scotland.

出版信息

Blood. 1996 Mar 1;87(5):1704-9.

PMID:8634415
Abstract

In this study, we assessed the effectiveness of interferon treatment in 31 hemophiliacs with chronic hepatitis C virus (HCV) infection. Interferon alfa-2a (3 MU three times weekly) was administered for 6 months. Response was assessed by both serial alanine transaminase (ALT) and HCV RNA levels measured by a sensitive semiquantitative polymerase chain reaction (PCR) method. HCV genotype was determined by restriction fragment length polymorphism (RFLP), and evidence of changing genotypes during interferon therapy was sought. Severity of liver disease was assessed by both noninvasive and invasive methods, including laparoscopic liver inspection and biopsy. Sustained normalization of ALT levels occurred in eight patients (28%), and seven (24%) became nonviremic as assessed by PCR (<80 HCV/mL). Responders universally cleared HCV RNA within 2 months of starting interferon. Genotype 3a was associated with a favorable response to interferon. No evidence was found for a change in circulating genotype in patients who failed to respond to interferon or who relapsed. This study confirms that response rates to interferon are low in hemophiliacs as compared with other groups with chronic HCV infection. We have also demonstrated that virus load measurement over the first 8 to 12 weeks of treatment is an extremely useful method to identify responders at an early stage.

摘要

在本研究中,我们评估了干扰素治疗31例慢性丙型肝炎病毒(HCV)感染血友病患者的疗效。给予α-2a干扰素(3MU,每周3次),持续6个月。通过连续监测丙氨酸转氨酶(ALT)水平以及采用灵敏的半定量聚合酶链反应(PCR)法检测HCV RNA水平来评估疗效。采用限制性片段长度多态性(RFLP)法确定HCV基因型,并探寻干扰素治疗期间基因型改变的证据。通过非侵入性和侵入性方法评估肝脏疾病的严重程度,包括腹腔镜肝脏检查和活检。8例患者(28%)ALT水平持续正常化,7例(24%)经PCR检测(<80 HCV/mL)转为非病毒血症。开始使用干扰素后2个月内,有反应者均清除了HCV RNA。3a基因型与对干扰素的良好反应相关。在对干扰素无反应或复发的患者中,未发现循环基因型改变的证据。本研究证实,与其他慢性HCV感染组相比,血友病患者对干扰素的反应率较低。我们还证明,在治疗的前8至12周测量病毒载量是早期识别有反应者的极其有用的方法。

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