Hassan Mohamed, Selimovic Denis, El-Khattouti Abdelouahid, Ghozlan Hanan, Haikel Youssef, Abdelkader Ola
Mohamed Hassan, Denis Selimovic, Youssef Haikel, National Institute of Health and Medical Research, U 977, Faculty of Medicine, and Dental Faculty, 11 Rue Humann, 67085 Strasbourg Cedex, France.
World J Exp Med. 2012 Apr 20;2(2):7-25. doi: 10.5493/wjem.v2.i2.7.
Hepatitis C virus (HCV) is a significant health problem facing the world. This virus infects more than 170 million people worldwide and is considered the major cause of both acute and chronic hepatitis. Persons become infected mainly through parenteral exposure to infected material by blood transfusions or injections with nonsterile needles. Although the sexual behavior is considered as a high risk factor for HCV infection, the transmission of HCV infection through sexual means, is less frequently. Currently, the available treatment for patients with chronic HCV infection is interferon based therapies alone or in combination with ribavirin and protease inhibitors. Although a sustained virological response of patients to the applied therapy, a great portion of patients did not show any response. HCV infection is mostly associated with progressive liver diseases including fibrosis, cirrhosis and hepatocellular carcinoma. Although the focus of many patients and clinicians is sometimes limited to that problem, the natural history of HCV infection (HCV) is also associated with the development of several extrahepatic manifestations including dermatologic, rheumatologic, neurologic, and nephrologic complications, diabetes, arterial hypertension, autoantibodies and cryglobulins. Despite the notion that HCV-mediated extrahepatic manifestations are credible, the mechanism of their modulation is not fully described in detail. Therefore, the understanding of the molecular mechanisms of HCV-induced alteration of intracellular signal transduction pathways, during the course of HCV infection, may offer novel therapeutic targets for HCV-associated both hepatic and extrahepatic manifestations. This review will elaborate the etiopathogenesis of HCV-host interactions and summarize the current knowledge of HCV-associated diseases and their possible therapeutic strategies.
丙型肝炎病毒(HCV)是全球面临的一个重大健康问题。该病毒在全球感染了超过1.7亿人,被认为是急性和慢性肝炎的主要病因。人们主要通过输血或使用非无菌针头注射等肠道外途径接触受感染物质而感染。虽然性行为被认为是HCV感染的高危因素,但通过性途径传播HCV感染的情况较少见。目前,慢性HCV感染患者可用的治疗方法是单独使用基于干扰素的疗法,或与利巴韦林和蛋白酶抑制剂联合使用。尽管患者对应用疗法有持续的病毒学应答,但很大一部分患者没有任何应答。HCV感染大多与包括纤维化、肝硬化和肝细胞癌在内的进行性肝病相关。虽然许多患者和临床医生有时将关注点局限于该问题,但HCV感染的自然史也与多种肝外表现的发生相关,包括皮肤、风湿、神经和肾脏并发症、糖尿病、动脉高血压、自身抗体和冷球蛋白。尽管认为HCV介导的肝外表现是可信的,但其调节机制尚未得到充分详细描述。因此,了解HCV感染过程中HCV诱导细胞内信号转导通路改变的分子机制,可能为HCV相关的肝内和肝外表现提供新的治疗靶点。本综述将阐述HCV与宿主相互作用的病因发病机制,并总结目前关于HCV相关疾病及其可能治疗策略的知识。