Detection of apoptotic caspase activation in sera from patients with chronic HCV infection is associated with fibrotic liver injury
Detection of apoptotic caspase activation in sera from patients with chronic HCV infection is associated with fibrotic liver injury
复制标题
DOI：
10.1002/hep.20411
复制
发表时间：
2004-11-01
期刊：
影响因子：
13.5
通讯作者：
Schulze-Osthoff, K
中科院分区：
文献类型：
--
作者：
Bantel, H;Lügering, A;Schulze-Osthoff, K
慢性丙型肝炎病毒(简称丙型肝炎病毒)感染以炎症性肝损害为特征，与发展为肝硬变和肝细胞癌的高风险相关。虽然肝活检的组织学检查是目前检测早期肝损害的金标准，但仍迫切需要更好的非侵入性方法。我们最近证实，在丙型肝炎病毒感染的肝组织切片中，caspase的促凋亡活性显著增强，这表明细胞凋亡在肝损伤中起着重要作用。在这里，我们调查了慢性丙型肝炎患者的血清中是否也可以检测到caspase的激活。使用一种新的酶联免疫吸附试验，选择性地识别caspase底物细胞角蛋白-18的蛋白水解性新表位，我们证明了在丙型肝炎患者的血清中caspase活性显著增加。有趣的是，虽然27%的慢性丙型肝炎患者在炎症和纤维化肝损伤的情况下转氨酶水平正常，但其中超过50%的患者血清caspase活性已经升高。此外，30%的转氨酶正常但caspase活性升高的患者显示出更高的纤维化阶段。综上所述，与传统的转氨酶等替代标志物相比，检测血清caspase活性可能是一种更敏感的早期肝损伤检测方法。因此，caspase活性的测定可能提供一种新的诊断工具，特别是对于转氨酶正常但在组织学上未被诊断为活动性肝炎和进行性纤维化的患者。
Chronic hepatitis C virus (HCV infection is characterized by inflammatory liver damage and is associated with a high risk of development of cirrhosis and hepatocellular carcinoma. Although histological examination of liver biopsies is currently the gold standard for the detection of early liver damage, there is a strong need for better noninvasive methods. We recently demonstrated that the proapoptotic activation of caspases is considerably enhanced in histological sections from HCV-infected liver tissue, suggesting an important role of apoptosis in liver damage. Here, we investigated whether caspase activation is detectable also in sera from patients with chronic HCV infection. Using a novel enzyme-linked immunosorbent assay that selectively recognizes a proteolytic neoepitope of the caspase substrate cytokeratin-18, we demonstrate that caspase activity is markedly increased in the sera of HCV patients. Interestingly, while 27% of patients with chronic HCV infection showed normal aminotransferase levels despite inflammatory and fibrotic liver damage, more than 50% of those patients exhibited already elevated serum caspase activity. Moreover, 30% of patients with normal aminotransferase but elevated caspase activity revealed higher stages of fibrosis. In conclusion, compared with conventional surrogate markers such as aminotransferases, detection of caspase activity in serum might be a more sensitive method of detecting early liver injury. Thus, measurement of caspase activity might provide a novel diagnostic tool, especially for patients with normal aminotransferases but otherwise undiagnosed histologically active hepatitis and progressive fibrosis.