The extent of liver steatosis in chronic hepatitis C virus infection is mirrored by caspase activity in serum
The extent of liver steatosis in chronic hepatitis C virus infection is mirrored by caspase activity in serum
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DOI：
10.1002/hep.20747
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发表时间：
2005-07-01
期刊：
影响因子：
13.5
通讯作者：
Bantel, H
中科院分区：
文献类型：
--
作者：
Seidel, N;Volkmann, X;Bantel, H
肝脏脂肪变性是慢性丙型肝炎病毒感染后的一种常见的组织学改变，它通过不清楚的机制使肝脏对细胞损伤、炎症和纤维化敏感。尽管细胞凋亡与多种肝病有关，但其在丙型肝炎相关脂肪变性中的重要性仍不清楚。在这项研究中，我们研究了细胞凋亡的关键调节因子caspase的作用，并采用两种新的caspase检测方法，即免疫学和发光酶试验，检测了不同程度脂肪变性的丙型肝炎患者血清中caspase的激活情况。我们的数据显示，不仅在肝活检组织中，而且在患有肝脏脂肪变性的丙型肝炎患者的血清中，也可以发现caspase活性的增加。脂肪变性患者的血清caspase活性水平明显高于正常健康人。此外，脂肪变性的程度与血清caspase活性密切相关，而特别是在轻度或中度脂肪变性的病例中，与转氨酶水平没有发现相关性。总之，在丙型肝炎相关的脂肪变性中，凋亡的caspase活性显著升高。更重要的是，我们的数据表明，caspase活性的测定可能是检测慢性丙型肝炎和其他肝病患者肝脏脂肪变性的敏感血清生物标志物。
Hepatic steatosis is a frequent histological alteration in chronic hepatitis C virus (HCV) infection that sensitizes the liver to cell injury, inflammation, and fibrosis via unclear mechanisms. Although apoptosis has been implicated in various liver diseases, its importance in HCV-associated steatosis is largely unknown. In this study, we investigated the role of caspases, the key regulators of apoptosis, and employed two novel caspase assays, an immunological and a luminometric enzyme test, to detect hepatic caspase activation in sera from HCV patients with different grades of steatosis. Our data show that increased caspase activation can be found not only in liver biopsies, but also in sera from HCV patients with liver steatosis. Patients with steatosis exhibited significantly higher serum levels of caspase activity compared with normal healthy individuals. Moreover, the extent of steatosis closely correlated with serum caspase activity, whereas in particular in cases of low or moderate steatosis, no correlation was found with aminotransferase levels. In conclusion, apoptotic caspase activation is considerably elevated in HCV-associated steatosis. More importantly, our data imply that measurement of caspase activation might be a sensitive serum biomarker to detect liver steatosis in patients with chronic HCV infection and other liver diseases.