Hepatitis C virus (HCV) and COVID-19 both affect the liver and cardiovascular systems, with the APOE4 allele playing a complex role in outcomes. APOE4 increases susceptibility to severe COVID-19, including heightened inflammation during ARDS, yet offers protection in HCV-related liver disease by reducing chronic infection, fibrosis, and cancer risk. This paradox, potentially linked to APOE4’s interactions with HSPGs and ACE2 receptors, highlights the need for further research into its role in viral entry and immune responses.

COVID-19 often causes transient liver involvement, marked by elevated liver enzymes due to direct viral damage, hypoxia, or inflammation. Chronic liver disease, particularly cirrhosis, increases COVID-19 mortality. APOE4 carriers face higher risks for severe COVID-19 but demonstrate protective effects in HCV, suggesting distinct pathways for viral infectivity and immune modulation. More studies are needed to clarify APOE4’s dual impact and its role in long COVID-19 and cardiovascular outcomes, offering potential targets for improved treatment strategies.

Reference: Lima FB, Bezerra KC, Nascimento JCR, Meneses GC, Oriá RB. Risk Factors for Severe COVID-19 and Hepatitis C Infections: The Dual Role of Apolipoprotein E4. Front Immunol. 2022;13:721793. doi: 10.3389/fimmu.2022.721793.