Volkmann Xandra, Cornberg Markus, Wedemeyer Heiner, Lehner Frank, Manns Michael P, Schulze-Osthoff Klaus, Bantel Heike
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Hepatology. 2006 Jun;43(6):1311-6. doi: 10.1002/hep.21186.
Only half of patients with chronic hepatitis C virus (HCV) infection and genotype-1 show a sustained antiviral response to the current antiviral therapy. The reason this treatment fails is unclear, and no reliable marker exists that predicts the treatment outcome. In the present study, we investigated the apoptotic activation of caspases in HCV patients undergoing antiviral therapy with regard to the treatment outcome. We determined caspase activation in sera from patients who were either responding or nonresponding to antiviral therapy by using two novel caspase assays, an immunological and a luminometric enzyme test. We found that compared with nonresponding individuals, responding patients showed significantly (P < .05) increased caspase activity, which was closely correlated with virus elimination (r = 0.81). The cutoff value of serum caspase activity was determined, which correctly predicted the treatment outcome with a sensitivity of 70% and a specificity of 82% (area under the curve 0.845; 95% CI). In conclusion, hepatic caspase activity might play a role in HCV clearance and could also predict the efficacy of antiviral therapy.
只有一半的慢性丙型肝炎病毒（HCV）感染且基因型为1型的患者对当前的抗病毒治疗表现出持续的抗病毒反应。这种治疗失败的原因尚不清楚，并且不存在可预测治疗结果的可靠标志物。在本研究中，我们针对治疗结果调查了接受抗病毒治疗的HCV患者中半胱天冬酶的凋亡激活情况。我们通过两种新型半胱天冬酶检测方法（一种免疫检测法和一种发光酶检测法）测定了对抗病毒治疗有反应或无反应患者血清中的半胱天冬酶激活情况。我们发现，与无反应个体相比，有反应的患者半胱天冬酶活性显著升高（P < 0.05），这与病毒清除密切相关（r = 0.81）。确定了血清半胱天冬酶活性的临界值，其预测治疗结果的灵敏度为70%，特异性为82%（曲线下面积0.845；95%置信区间）。总之，肝脏半胱天冬酶活性可能在HCV清除中起作用，并且还可以预测抗病毒治疗的疗效。
