The Coronavirus Disease 2019 (COVID-19) pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has revealed the virus's ability to induce multi-organ damage, including significant liver injury. The molecular mechanisms of liver dysfunction in COVID-19 patients are explored, focusing on direct viral infection, immune-mediated damage, and the gut-liver axis. SARS-CoV-2 enters liver cells through the Angiotensin-Converting Enzyme 2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) receptors, but alternative pathways, such as CD209/Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN) and AXL receptors, can also contribute to viral entry. Additionally, immune responses, particularly the cytokine storm, exacerbate liver inflammation, leading to hepatocyte damage. Pre-existing liver conditions, such as metabolic-associated fatty liver disease (MAFLD), alcohol-related liver disease (ALD), and liver fibrosis, heighten the risk of severe outcomes in COVID-19 patients. Post-COVID-19 liver complications, including fibrosis progression and persistent liver damage, have been reported, with emerging evidence suggesting chronic inflammation, viral persistence, and autoimmune reactions as potential contributors. Furthermore, Drug-Induced Liver Injury (DILI) from COVID-19 treatments remains a concern, highlighting the need for careful management. Consequently, understanding the interplay between SARS-CoV-2 and the liver is critical for improving patient outcomes and developing targeted therapies to mitigate liver-related complications in both acute and Long COVID-19 phases. This article is categorized under: Infectious Diseases > Molecular and Cellular Physiology.
