Castro F J, Esteban J I, Juárez A, Sauleda S, Viladomiu L, Martell M, Moreno F, Allende H, Esteban R, Guardia J
Liver Unit, Department of Medicine, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
J Viral Hepat. 2002 May;9(3):202-7. doi: 10.1046/j.1365-2893.2002.00348.x.
We have investigated the value of early hepatitis C virus (HCV) RNA decline (DeltaHCV RNA) to predict response to combination therapy in 66 chronic hepatitis C patients treated with IFN-alpha2b (3 MU thrice weekly) and ribavirin (800 mg daily) for 12 months [25 sustained responders (SR) and 41 nonresponders or relapsers (NR)]. Serum HCV RNA was retrospectively measured in samples obtained at baseline and 4, 8 and 12 weeks after treatment onset, using a commercially available quantitative RT-PCR assay. At 4 weeks, serum HCV RNA had decreased a mean of 2.6 +/- 0.8 logs among SR as compared with only 0.5 +/- 0.8 logs in NR (P < 0.001), and was already undetectable (< 600 IU/mL) in 12 (48%) of the SR but in none of the NR. At 8 weeks, HCV RNA was undetectable in 21 SR and in 2 NR and mean DeltaHCV RNA were 4.2 +/- 1.3 and 0.8 +/- 1.0 logs, respectively (P < 0.001). At week 12 all SR had undetectable HCV RNA as compared with only five NR (P < 0.001). Stepwise logistic regression analysis identified DeltaHCV RNA at 12 weeks as the strongest predictor of sustained response. Receiver operating characteristic (ROC) curves of DeltaHCV RNA for sustained response prediction identified sensitivity peaks with 100% negative predictive value corresponding to DeltaHCV RNA > 1 log at 4 weeks, > 2 logs at 8 weeks and > 3 logs at 12 weeks. Our results show that early changes in the HCV RNA level may reliably identify patients having no chance of a sustained virological response during the first 3 months of combination therapy, thus providing an excellent tool for optimizing antiviral treatment of chronic hepatitis C.
我们研究了早期丙型肝炎病毒（HCV）RNA下降幅度（ΔHCV RNA）对预测66例慢性丙型肝炎患者联合治疗反应的价值。这些患者接受了α-2b干扰素（3 MU，每周3次）和利巴韦林（800 mg，每日1次）治疗12个月[25例持续应答者（SR）和41例无应答者或复发者（NR）]。使用市售定量逆转录聚合酶链反应（RT-PCR）检测法，对治疗开始时、治疗后4周、8周和12周采集的样本进行回顾性血清HCV RNA检测。在4周时，SR组血清HCV RNA平均下降2.6±0.8 log，而NR组仅下降0.5±0.8 log（P<0.001），12例（48%）SR患者的血清HCV RNA已检测不到（<600 IU/mL），而NR组无一例检测不到。在8周时，21例SR患者和2例NR患者的HCV RNA检测不到，平均ΔHCV RNA分别为4.2±1.3 log和0.8±1.0 log（P<0.001）。在12周时，所有SR患者的HCV RNA均检测不到，而只有5例NR患者检测不到（P<0.001）。逐步逻辑回归分析确定12周时的ΔHCV RNA是持续应答的最强预测指标。用于预测持续应答的ΔHCV RNA的受试者工作特征（ROC）曲线显示，4周时ΔHCV RNA>1 log时，阴性预测值为100%，敏感性达到峰值；8周时>2 log；12周时>3 log。我们的结果表明，HCV RNA水平的早期变化可以可靠地识别在联合治疗的前3个月内没有持续病毒学应答机会的患者，从而为优化慢性丙型肝炎的抗病毒治疗提供了一个很好的工具。
