The Translational Bridge between Inflammation and Hepatocarcinogenesis

Cells. 2022 Feb 3;11(3):533. doi: 10.3390/cells11030533.

Abstract

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.

Keywords: acute hepatitis; alcoholic liver disease (ALD); autoimmune hepatitis; chronic hepatitis; cirrhosis; eukaryotic translation initiation factors (eIFs); hepatitis virus; hepatocellular carcinoma (HCC); mTOR signaling; non-alcoholic fatty liver disease (NAFLD); steatosis.

Publication types

  • Review

MeSH terms

  • Carcinogenesis
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / metabolism
  • Ethanol
  • Hepatitis, Viral, Human*
  • Humans
  • Inflammation
  • Liver Cirrhosis
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / metabolism
  • Non-alcoholic Fatty Liver Disease*
  • TOR Serine-Threonine Kinases

Substances

  • Ethanol
  • TOR Serine-Threonine Kinases