University of Chicago Medical Center, Center for Liver Disease, Chicago, Illinois 60637, USA.
Am J Gastroenterol. 2011 Mar;106(3):452-8. doi: 10.1038/ajg.2010.424. Epub 2010 Nov 9.
Early viral kinetics accurately predicts sustained virological response (SVR) in genotype 1 patients with hepatitis C virus (HCV) undergoing therapy with pegylated interferon (PEG) and ribavirin (RBV). No baseline factor has a stronger predictive role. Early identification of patients unlikely to respond is equally important, allowing early treatment modification or discontinuation. The aim of this study was to determine whether 4-week null response (eNR) correlates directly with 12-week null response and inversely with SVR.
A retrospective analysis of HCV patients treated at our institution was done. Patients were classified based on a 4-week viral log decline compared with baseline: <1 log, ≥ 1 log, <2 log, ≥ 2 log, <3 log, ≥ 3 log without rapid virological response (RVR) and with RVR. eNR was defined as less than a 1 log change from baseline.
A total of 159 patients had quantitative HCV-RNA PCR at treatment week 4, of whom 24% (38) experienced eNR. In all, 22 (58%) of the eNR patients were African American, 58% male, 32% cirrhotic, average age 53 years (range 36-71), 89% (33) genotype 1, and average baseline viral load was 5.9261 log (range 3.1492-7.3025). On-treatment response demonstrated failure to attain early virological response (EVR; 2-log decline at week 12) in 50% (19) and partial EVR (pEVR) in 39% (15). Three (8%) patients with eNR achieved SVR. In our patient population, eNR had 92% negative predictive value (confidence interval 83.5-100%) for SVR and was the strongest single predictor for treatment failure, including the baseline factors genotype and viral load.
eNR is strongly associated with null response or pEVR and accurately predicts failure to attain SVR. Consideration should be made to discontinue or modify therapy in patients with eNR who receive the appropriate weight-based PEG/RBV.
在接受聚乙二醇（PEG）和利巴韦林（RBV）治疗的 HCV 基因型 1 患者中，早期病毒动力学可准确预测持续病毒学应答（SVR）。没有哪种基线因素具有更强的预测作用。同样重要的是，早期识别不太可能产生应答的患者，以便早期进行治疗修改或停药。本研究旨在确定 4 周无应答（eNR）是否与 12 周无应答直接相关，以及与 SVR 成反比。
对我院治疗的 HCV 患者进行回顾性分析。根据与基线相比 4 周时的病毒对数下降情况对患者进行分类：<1 个对数、≥1 个对数、<2 个对数、≥2 个对数、<3 个对数、≥3 个对数但无快速病毒学应答（RVR）和有 RVR。eNR 定义为与基线相比变化小于 1 个对数。
共有 159 例患者在治疗第 4 周进行了 HCV-RNA PCR 定量检测，其中 24%（38 例）发生 eNR。在所有 eNR 患者中，22 例（58%）为非裔美国人，58%为男性，32%为肝硬化，平均年龄为 53 岁（范围 36-71），89%（33 例）为基因型 1，平均基线病毒载量为 5.9261 log（范围 3.1492-7.3025）。在治疗过程中，50%（19 例）患者未能达到早期病毒学应答（EVR；第 12 周时下降 2 个对数），39%（15 例）患者为部分 EVR（pEVR）。3 例（8%）eNR 患者获得 SVR。在我们的患者人群中，eNR 对 SVR 的阴性预测值为 92%（置信区间 83.5-100%），是治疗失败的最强单一预测因素，包括基线因素基因型和病毒载量。
eNR 与无应答或 pEVR 密切相关，可准确预测无法达到 SVR。对于接受适当体重 PEG/RBV 治疗的 eNR 患者，应考虑停药或修改治疗方案。
