Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, Nebraska 68105, USA.
Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
Alcohol Alcohol. 2021 Jan 4;56(1):8-16. doi: 10.1093/alcalc/agaa085.
Chronic and excessive alcohol abuse cause direct and indirect detrimental effects on a wide range of body organs and systems and accounts for ~4% of deaths worldwide. Many factors influence the harmful effects of alcohol. This concise review presents newer insights into the role of select second hits in influencing the progression of alcohol-induced organ damage by synergistically acting to generate a more dramatic downstream biological defect. This review specifically addresses on how a lifestyle factor of high fat intake exacerbates alcoholic liver injury and its progression. This review also provides the mechanistic insights into how increasing matrix stiffness during liver injury promotes alcohol-induced fibrogenesis. It also discusses how hepatotropic viral (HCV, HBV) infections as well as HIV (which is traditionally not known to be hepatotropic), are potentiated by alcohol exposure to promote hepatotoxicity and fibrosis progression. Finally, this review highlights the impact of reactive aldehydes generated during alcohol and cigarette smoke coexposure impair innate antimicrobial defense and increased susceptibility to infections. This review was inspired by the symposium held at the 17th Congress of the European Society for Biomedical research on Alcoholism in Lille, France entitled 'Second hits in alcohol-related organ damage'.
慢性和过度酗酒会对人体的广泛器官和系统造成直接和间接的有害影响，约占全球死亡人数的 4%。许多因素会影响酒精的有害影响。本综述介绍了一些新的见解，即选择的二次打击如何通过协同作用产生更明显的下游生物学缺陷，从而影响酒精引起的器官损伤的进展。本综述特别探讨了高脂肪饮食这种生活方式因素如何加剧酒精性肝损伤及其进展。本综述还提供了在肝损伤过程中细胞外基质硬度增加如何促进酒精诱导的纤维化的机制见解。还讨论了丙型肝炎病毒（HCV）、乙型肝炎病毒（HBV）（传统上不被认为是嗜肝病毒）等嗜肝病毒感染以及艾滋病毒（HIV）（传统上不被认为是嗜肝病毒）如何在酒精暴露的情况下被增强，从而促进肝毒性和纤维化的进展。最后，本综述强调了在酒精和香烟烟雾共同暴露过程中产生的反应性醛类物质如何损害先天的抗菌防御并增加感染的易感性。这篇综述的灵感来自于在法国里尔举行的第 17 届欧洲酒精相关生物医学研究学会大会上题为“酒精相关器官损伤中的二次打击”的研讨会。
