Prediction of relapse following treatment for hepatitis C: is whole blood more than the sum of its parts?
Prediction of relapse following treatment for hepatitis C: is whole blood more than the sum of its parts?
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丙型肝炎治疗后复发的预测：全血是否大于各部分的总和？
DOI：
10.1086/425619
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Koziel,MargaretJames
中科院分区：
文献类型：
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作者：
Shire,Norah;Koziel,MargaretJames
丙型肝炎病毒（HCV）的治疗持续时间长、价格昂贵，并且对患者和医疗保健专业人员来说具有挑战性。目前的治疗方案包括聚乙二醇干扰素（每周注射一次）和利巴韦林（每日给药），持续24-48周，具体取决于病毒基因型。这些药物的联合毒性包括抑郁（可能是重度）、发热、流感样综合征和多种血液学异常，包括贫血、中性粒细胞减少和血小板减少。这些药物每年可能花费数千美元，每周注射的要求加上流感样疾病的持续时间延长，要求临床医生为选择接受治疗的患者提供相当大的支持。持续病毒学应答率（常规定义为治疗完成后24周无血清病毒血症）差异很大，取决于基因型和其他宿主因素[1]，在临床试验中，HCV基因型2和3感染患者的持续病毒学应答率为80%-90%，而基因型1感染的其他健康患者的持续病毒学应答率为40%-50%。然而，在社区实践中，该方案带来的实质性障碍导致接受药物治疗并实现持续病毒学应答的患者少得多[2]。显然，临床医生和患者都对早期预测未能实现持续病毒学应答感兴趣，以最大限度地减少不必要的毒性和费用。在这一期的临床传染病，沃特金斯里德尔等人。[3]解决丙型肝炎初步成功治疗后复发的实验室预测问题。本研究比较了治疗结束前后血清、血浆和全血标本中RNA阳性的动力学。一组对初始标准剂量IFN单药治疗无反应的患者接受高剂量标准IFN单药治疗或与利巴韦林联合治疗。选择五十六例连续患者，从研究第24周（治疗结束前24周）开始，每4周进行一次血清、血浆和全血中HCV RNA检测，并持续至治疗结束后24周。在这些患者中，18例在治疗结束时血清中HCV RNA的检测结果为阴性，14例最终复发。Watkins-Riedel等人[3]发现治疗结束时全血中HCV RNA的检测对病毒复发具有很强的阳性预测价值。持续病毒学应答的阴性预测值较低，但可能受到获得持续病毒学应答的患者数量较少的限制，这不是第一个比较全血和血浆或血清中HCV RNA检测的研究。一些研究先前已经表明，使用“自制”方法进行提取和分析，全血中的HCV RNA拷贝数比血浆中的多[4-6]。然而，在其中一项研究中注意到的局限性[4]是最初无法用市售检测试剂盒（Amplicor; Roche Diagnostics）确认全血分析的结果，这可能是由于自制方法中使用的RNA浓度较高。当另一组无法使用相同的提取技术验证这些结果时，另一个争议来源出现了[7]。在本研究中，Watkins-Riedel et al. [3]他们谨慎地使用商业上可获得的测定来验证他们的结果，这是朝着更广泛地使用全血测定而不是血清测定迈出的重要一步。放在以前的研究背景下，这项研究告诉我们什么？
Therapy for hepatitis C virus (HCV) has a long duration, is expensive, and is challenging for the patient and the health care professional. The current regimen consists of pegylated IFN (injected once weekly) and ribavirin (administered daily) together for 24–48 weeks, depending on the viral genotype. Combined toxicities of these medications include depression (which may be severe), fever, flulike syndrome, and multiple hematologic abnormalities, including anemia, neutropenia, and thrombocytopenia. These medications can cost thousands of dollars per year, and the requirement of weekly injections combined with the prolonged duration of flulike illness require clinicians to provide considerable support to patients who elect to be treated. Rates of sustained virologic response (conventionally defined as the absence of serum viremia 24 weeks after completion of treatment) vary widely, depending on the genotype and other host factors [1], and in clinical trials range from 80%–90% in patients with HCV genotype 2 and 3 infection to 40%–50% in otherwise healthy patients with genotype 1 infection. However, in community practice, the substantial barriers presented by this regimen result in far fewer patients receiving medication and achieving a sustained virologic response [2]. Obviously, both clinicians and patients have a substantial interest in early prediction of failure to achieve sustained virologic response, to minimize both unwarranted toxicities and costs. In this issue of Clinical Infectious Diseases, Watkins-Riedel et al.[3] address the issue of laboratory prediction of relapse after initially successful treatment of hepatitis C. This study compared the kinetics of RNA positivity in serum, plasma, and whole-blood specimens both before and after the end of treatment. A group of patients who did not respond to initial standard-dose IFN monotherapy were treated with high-dose standard IFN alone or in combination with ribavirin. Fifty-six sequential patients were chosen to undergo testing for detection of HCV RNA in serum, plasma, and whole blood every 4 weeks, beginning at week 24 of the study (24 weeks before the end of treatment) and continuing through week 24 after the end of treatment. Of these patients, 18 had negative tests results for the presence of HCV RNA in serum at the end of treatment, and 14 ultimately relapsed. Watkins-Riedel et al.[3] found that detection of HCV RNA in whole blood at the end of treatment had a strong positive predictive value for viral relapse. The negative predictive value for sustained virologic response was lower but may have been limited by the small number of patients who achieved a sustained virologic response.This is not the first study to compare HCV RNA detection in whole blood with that in plasma or serum. Several studies have previously shown, using “homebrew” methods for extraction and analysis, that there are more HCV RNA copies in whole blood than in plasma [4–6]. However, a limitation noted in one of these studies [4] was the initial inability to confirm the results of whole-blood analysis with a commercially available assay (Amplicor; Roche Diagnostics), which was probably due to higher concentrations of RNA used in the home-brew method. An additional source of controversy arose when another group was unable to validate these results using the same extraction techniques [7]. In the present study, Watkins-Riedel et al.[3] were careful to validate their results using commercially available assays, which is an important step toward wider use of whole-blood assays instead of serum assays. Placed in the context of previous research, what does this study tell us about