A new study has found that individuals with fatty liver disease may be more susceptible to severe COVID-19. Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), also known as Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH), affects a significant portion of the global population. This liver disorder is characterized by the buildup of fat in the liver, inflammation, fibrosis, and the development of pre-cancerous cells.
Researchers discovered that individuals with MASLD have higher levels of a cell surface protein called Angiotensin-converting enzyme 2 (ACE2), which is the primary receptor for the SARS-CoV-2 virus responsible for COVID-19. This increased availability of ACE2 receptors in the liver puts patients with fatty liver disease at a greater risk of experiencing severe COVID-19 and liver injury.
The study focused on understanding the expression levels and cellular sources of ACE2 and its co-receptors in MASLD and other fibroinflammatory liver diseases. Although the respiratory system is the primary site of infection for SARS-CoV-2, viral RNA has been detected in liver tissues, suggesting that the liver may also be a target for viral infection. Therefore, investigating the expression and distribution of ACE2 in the liver becomes crucial, especially in the context of MASLD.
ACE2 plays a vital role in regulating the renin-angiotensin-aldosterone system (RAAS), which controls blood pressure and fluid and electrolyte balance. ACE2 cleaves angiotensin II (Ang II) into Ang1-7, which activates the MAS1 receptor and leads to various physiological effects. Activation of the ACE2/Ang1-7/MAS axis can improve lipid metabolism and glucose metabolism, which are crucial in addressing the imbalances seen in NAFLD and NASH. Therefore, understanding the role of ACE2 in liver physiology is essential.
The study found that ACE2 expression is upregulated in patients with fatty liver disease, particularly those with steatohepatitis. This upregulation is associated with liver fat content, inflammation, increased immune reactivity, and fibrogenesis. Additionally, ACE2 expression was found to be upregulated in overweight patients with fatty liver disease. However, ACE2 expression was not significantly altered in patients with alcoholic or viral hepatitis.
Experiments with human hepatocytes in vitro showed that long-chain fatty acids induce ACE2 mRNA expression, indicating that the excess of fatty acids characteristic of fatty liver disease plays a crucial role in the upregulation of ACE2 expression. Conversely, treatment with inflammatory cytokines alone did not lead to an increase in ACE2 expression in the liver. This suggests that the regulation of ACE2 in the liver is specific to fatty acids and may not be influenced by inflammation alone.
The implications of this research are significant for clinical practice and further research. Patients with fatty liver disease, especially those with steatohepatitis, are at a higher risk of severe COVID-19 and liver injury due to increased ACE2 availability. Healthcare providers should be aware of this vulnerability and consider implementing timely vaccination boosters for this population. Dietary adjustments, such as controlling the intake of specific fatty acids, may help manage fatty liver disease and reduce the risk of severe COVID-19 and liver complications. Stricter hygiene practices and protective measures are also recommended for patients with fatty liver disease to minimize the risk of SARS-CoV-2 exposure. This study opens the door for further research into the complex interplay between fatty liver disease, ACE2 expression, and viral infection, potentially leading to novel therapeutic targets for both COVID-19 and fatty liver disease.
In conclusion, this research provides valuable insights into the relationship between fatty liver disease and the expression of ACE2, the receptor for SARS-CoV-2. Patients with MASLD are shown to have increased ACE2 expression, particularly in the presence of steatohepatitis and in overweight individuals. The study suggests potential strategies for risk reduction, including dietary modifications and enhanced hygiene practices. Healthcare providers and researchers can use these findings to protect vulnerable patients and develop effective treatment strategies. Further studies are needed to explore the underlying molecular mechanisms and potential therapeutic interventions related to ACE2 in the context of fatty liver disease and COVID-19.