文章：

HBV和HCV相关肝细胞癌的发病机制

Pathogenic mechanisms in HBV- and HCV-associated hepatocellular carcinoma

原文发布日期：2013-01-24

DOI: 10.1038/nrc3449

类型: Review Article

开放获取: 否

要点：

1. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major aetiological agents of chronic liver disease and hepatocellular carcinoma (HCC). HCC is the fifth most prevalent tumour type and the third leading cause of cancer-related deaths worldwide, which is why it is so important to find early diagnostic markers and therapeutic targets, particularly when these markers and targets are common to both chronic infections.
2. Alterations in multiple signalling pathways and patterns of host gene expression have been documented following HBV and HCV infections, but their relative importance to the pathogenesis of HCC has not been clearly defined. This has limited the ability to design appropriate therapeutic intervention strategies, and to determine the best time during chronic infection for their application.
3. The pathogenesis of HBV and HCV infections is generally immune mediated, although these viruses have evolved multiple mechanisms to escape immune elimination and to continue replicating in an infected host for many years.
4. Chronic infection with either virus can result in inflammation and oxidative stress. A prolonged fibrotic response, resulting in cirrhosis, is also common in both infections, which is accompanied by the appearance of localized hypoxia, rearrangement of tissue architecture (epithelial–mesenchymal transition) and angiogenesis.
5. Altered host gene expression in chronic liver disease may be mediated by epigenetic changes, by inhibition of DNA repair and/or by differential expression of microRNAs. These alterations include constitutive upregulated expression of factors involved in 'stemness', suggesting that both viruses may contribute to HCC by promoting stemness.
6. Early biomarkers and tumour-specific treatments for HCC are mostly lacking, although several signalling cascades that are activated in the liver before tumour appearance suggest that oncogene addiction may be important to the pathogenesis of HCC.
7. Understanding common mechanisms of HBV and HCV pathogenesis will help to focus efforts on therapeutic targets that may be most useful in the development of new treatment approaches.

要点翻译：

1. 乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）是慢性肝病及肝细胞癌（HCC）的主要致病因素。肝细胞癌在全球肿瘤发病率中位列第五，在癌症相关死因中高居第三，这正凸显了寻找早期诊断标志物和治疗靶点的重要性——尤其当这些标志物和靶点对两种慢性感染具有共通性时。
2. HBV和HCV感染会引发多重信号通路改变及宿主基因表达模式变化，但这些改变对HCC发病机制的相对重要性尚未明确。这种认知局限制约了合理治疗干预策略的设计，也影响了确定慢性感染过程中最佳干预时机的判断。
3. 虽然这两种病毒已进化出多种免疫逃逸机制，能在感染宿主体内持续复制多年，但HBV和HCV的致病过程通常由免疫介导。
4. 任一病毒的慢性感染均可引发炎症反应和氧化应激。两种感染中也常见纤维化反应持续进展导致肝硬化，并伴随局部缺氧现象、组织架构重塑（上皮-间质转化）以及血管生成。
5. 慢性肝病中宿主基因表达的异常可能通过表观遗传改变、DNA修复抑制和/或microRNAs差异表达来实现。这些改变包括“干性”相关因子的持续性上调表达，提示两种病毒可能通过促进干性特征参与HCC的发生。
6. 目前仍缺乏针对HCC的早期生物标志物和肿瘤特异性疗法，不过在肿瘤出现前肝脏中激活的若干信号通路提示，癌基因成瘾性可能对HCC发病机制具有重要作用。
7. 理解HBV和HCV致病的共同机制，将有助于聚焦最具潜力的治疗靶点，为开发新型治疗方案指引方向。

英文摘要：

Hepatocellular carcinoma (HCC) is a highly lethal cancer, with increasing worldwide incidence, that is mainly associated with chronic hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections. There are few effective treatments partly because the cell- and molecular-based mechanisms that contribute to the pathogenesis of this tumour type are poorly understood. This Review outlines pathogenic mechanisms that seem to be common to both viruses and which suggest innovative approaches to the prevention and treatment of HCC.

摘要翻译： 

肝细胞癌（HCC）是一种高度致命的癌症，全球发病率不断上升，主要与慢性乙型肝炎病毒（HBV）和/或丙型肝炎病毒（HCV）感染相关。目前有效治疗手段有限，部分原因在于对该肿瘤类型发病机制中细胞和分子层面的基础机制了解甚少。本文综述了这两种病毒共有的致病机制，并提出了预防及治疗HCC的创新策略。

原文链接：

Pathogenic mechanisms in HBV- and HCV-associated hepatocellular carcinoma