Histone Deacetylase Inhibitors Promising Therapeutic Target for Liver Diseases

Abstract: Despite enormous advances in the current treatment strategies, liver diseases are associated with high mortality. It is critical to discover novel drug targets for developing effective therapies. Histone deacetylase (HDAC) inhibitors have emerged as a promising therapeutic approach for the treatment of various liver diseases. The use of histone deacetylases and their inhibitors to treat a variety of liver illnesses has been thoroughly reviewed using suitable keywords and key phrases as search terms within scientific databases like Web of Science, Google Scholar, PubMed, and other web sources, and data was collected and sorted from the literature spanning from 1990 to 2023, providing an overview of the role of HDACs in liver diseases together with the evidence of the therapeutic effects of HDAC inhibitors in various liver diseases. HDACs are enzymes that play a crucial role in regulating gene expression by deacetylating histone proteins, which can alter chromatin structure and thereby regulate gene expression. Dysregulation of HDAC activity is associated with liver diseases, including Hepatocellular carcinoma (HCC), non-alcoholic fatty liver disease (NAFLD), hepatitis B virus (HBV), and hepatitis C virus (HCV) infections, etc. as implicated in many studies both in vitro and in vivo. This review summarizes the prevalence of liver diseases and how their impact is significant. We highlight the crucial role of histone deacetylases (HDACs) in liver diseases. In addition, by targeting various mechanisms, HDAC inhibitors have shown promise as novel hepatoprotective agents. These inhibitors can have therapeutic effects in different liver diseases. They can induce cell cycle arrest, promote apoptosis, improve insulin resistance, address hepatic steatosis, and enhance differentiation in hepatocellular carcinoma (HCC) cells. The multifaceted approach of HDAC inhibitors offers potential for innovative treatments in liver diseases.