Bartosch Birke, Thimme Robert, Blum Hubert E, Zoulim Fabien
INSERM, U871, 151 Cours Albert Thomas, 69003 Lyon, France.
J Hepatol. 2009 Oct;51(4):810-20. doi: 10.1016/j.jhep.2009.05.008. Epub 2009 May 23.
Although there is strong evidence that hepatitis C virus (HCV) is one of the leading causes of hepatocellular carcinoma (HCC), there is still much to understand regarding the mechanism of HCV-induced transformation. While liver fibrosis resulting from long-lasting chronic inflammation and liver regeneration resulting from immune-mediated cell death are likely factors that contribute to the development of HCC, the direct role of HCV proteins remains to be determined. In vitro studies have shown that HCV expression may interfere with cellular functions that are important for cell differentiation and cell growth. However, most studies were performed in artificial models which can only give clues for potential mechanisms that need to be confirmed in more relevant models. Furthermore, the difficulty to identify HCV proteins and infected liver cells in patients, contributes to the complexity of our current understanding. For these reasons, there is currently very little experimental evidence for a direct oncogenic role of HCV. Further studies are warranted to clarify these issues.
尽管有强有力的证据表明丙型肝炎病毒(HCV)是肝细胞癌(HCC)的主要病因之一,但关于HCV诱导细胞转化的机制仍有许多有待了解之处。虽然长期慢性炎症导致的肝纤维化以及免疫介导的细胞死亡引起的肝再生可能是促成HCC发生发展的因素,但HCV蛋白的直接作用仍有待确定。体外研究表明,HCV表达可能会干扰对细胞分化和细胞生长至关重要的细胞功能。然而,大多数研究是在人工模型中进行的,这些模型只能为潜在机制提供线索,而这些机制需要在更相关的模型中得到证实。此外,在患者中识别HCV蛋白和受感染肝细胞存在困难,这增加了我们目前理解的复杂性。由于这些原因,目前几乎没有实验证据表明HCV具有直接致癌作用。有必要进行进一步研究以阐明这些问题。