Department of Medicine, LRB215 University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
Alcohol Clin Exp Res. 2010 Oct;34(10):1675-86. doi: 10.1111/j.1530-0277.2010.01255.x. Epub 2010 Jan 20.
Hepatitis C virus infection affects 170 million people worldwide, and the majority of individuals exposed to HCV develop chronic hepatitis leading to progressive liver damage, cirrhosis, and hepatocellular cancer. The natural history of HCV infection is influenced by genetic and environmental factors of which chronic alcohol use is an independent risk factor for cirrhosis in HCV-infected individuals. Both the hepatitis C virus and alcohol damage the liver and result in immune alterations contributing to both decreased viral clearance and liver injury. This review will capture the major components of the interactions between alcohol and HCV infection to provide better understanding for the molecular basis of the dangerous combination of alcohol use and HCV infection. Common targets of HCV and alcohol involve innate immune recognition and dendritic cells, the critical cell type in antigen presentation and antiviral immunity. In addition, both alcohol and HCV affect intracellular processes critical for hepatocyte and immune cell functions including mitochondrial and proteasomal activation. Finally, both chronic alcohol use and hepatitis C virus infection increase the risk of hepatocellular cancer. The common molecular mechanisms underlying the pathological interactions between alcohol and HCV include the modulation of cytokine production, lipopolysaccharide (LPS)-TLR4 signaling, and reactive oxygen species (ROS) production. LPS-induced chronic inflammation is not only a major cause of progressive liver injury and fibrosis, but it can also contribute to modification of the tissue environment and stem cells to promote hepatocellular cancer development. Alteration of these processes by alcohol and HCV produces an environment of impaired antiviral immune response, greater hepatocellular injury, and activation of cell proliferation and dedifferentiation.
丙型肝炎病毒感染影响全球 1.7 亿人，大多数接触 HCV 的个体发展为慢性肝炎，导致进行性肝损伤、肝硬化和肝细胞癌。HCV 感染的自然史受遗传和环境因素的影响，其中慢性酒精使用是 HCV 感染个体发生肝硬化的独立危险因素。HCV 和酒精均可损害肝脏，并导致免疫改变，从而导致病毒清除和肝损伤减少。这篇综述将捕捉到酒精和 HCV 感染之间相互作用的主要成分，为更好地理解酒精使用和 HCV 感染这一危险组合的分子基础提供更好的理解。HCV 和酒精的常见靶点涉及先天免疫识别和树突状细胞，这是抗原呈递和抗病毒免疫的关键细胞类型。此外，酒精和 HCV 均影响肝细胞和免疫细胞功能的关键细胞内过程，包括线粒体和蛋白酶体激活。最后，慢性酒精使用和丙型肝炎病毒感染都会增加肝细胞癌的风险。酒精和 HCV 之间病理相互作用的共同分子机制包括细胞因子产生、脂多糖 (LPS)-TLR4 信号和活性氧 (ROS) 产生的调节。LPS 诱导的慢性炎症不仅是进行性肝损伤和纤维化的主要原因，而且还可以促进组织环境和干细胞的改变，以促进肝细胞癌的发展。酒精和 HCV 对这些过程的改变会产生抗病毒免疫反应受损、肝细胞损伤更大以及细胞增殖和去分化激活的环境。
