Institute of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, 6020 Innsbruck, Austria.
Clinical Institute of Pathology, University Hospital St. Poelten, Karl Landsteiner University of Health Sciences, 3100 St. Poelten, Austria.
Cells. 2022 Feb 3;11(3):533. doi: 10.3390/cells11030533.
Viral infections or persistent alcohol or drug abuse, together with intrinsic factors, lead to hepatitis, which often ends in the development of liver cirrhosis or hepatocellular carcinoma (HCC). With this review, we describe inflammatory liver diseases, such as acute liver failure, virus-induced hepatitis, alcoholic- and non-alcoholic steatohepatitis, and autoimmune hepatitis, and highlight their driving mechanisms. These include external factors such as alcohol misuse, viral infection and supernutrition, as well as intrinsic parameters such as genetic disposition and failure, in immune tolerance. Additionally, we describe what is known about the translational machinery within all these diseases. Distinct eukaryotic translation initiation factors (eIFs) with specific functional roles and aberrant expression in HCC are reported. Many alterations to the translational machinery are already triggered in the precancerous lesions described in this review, highlighting mTOR pathway proteins and eIFs to emphasize their putative clinical relevance. Here, we identified a lack of knowledge regarding the roles of single eIF proteins. A closer investigation will help to understand and treat HCC as well as the antecedent diseases.
病毒感染或长期酗酒、吸毒，再加上内在因素，导致肝炎，常发展为肝硬化或肝细胞癌（HCC）。通过本文综述，我们描述了炎症性肝病，如急性肝衰竭、病毒引起的肝炎、酒精性和非酒精性脂肪性肝炎以及自身免疫性肝炎，并强调了它们的驱动机制。这些机制包括酒精滥用、病毒感染和营养过剩等外在因素，以及免疫耐受中的遗传易感性和衰竭等内在因素。此外，我们还描述了所有这些疾病中转录机制的相关知识。已有报道称，在 HCC 中存在具有特定功能作用和异常表达的不同真核起始因子（eIF）。在本文综述中描述的癌前病变中，已经触发了许多对翻译机制的改变，突出了 mTOR 通路蛋白和 eIF 的作用，以强调它们的潜在临床相关性。在这里，我们发现了对单个 eIF 蛋白作用的认识不足。更深入的研究将有助于理解和治疗 HCC 以及其前身疾病。
