What Has the COVID-19 Pandemic Taught Us so Far? Addressing the Problem from a Hepatologist’s Perspective

Méndez-Sánchez, Nahum; Valencia-Rodríguez, Alejandro; Qi, Xingshun; Yoshida, Eric M.; Romero-Gómez, Manuel; George, Jacob; Eslam, Mohammed; Abenavoli, Ludovico; Xie, Weifen; Teschke, Rolf; Carrion, Andres F.; Keaveny, Andrew P.

It is a matter of debate whether COVID-19 is directly responsible for the development of liver injury, or whether the observed changes are secondary to the systemic inflammation triggered by infection (Fig. 1) . The Chinese Digestion Association of the Chinese Medical Doctor Association and the Chinese Society of Hepatology of the Chinese Medical Association recently stated that the development of liver injury in COVID-19 patients might be related to any of the following: 1) a direct hit from this virus; 2) systemic inflammation; 3) hepatic ischemia and hypoxia; 4) pre-existing liver disease; and 5) drug-related liver injury (especially the use of antibiotics or other hepatotoxic drugs in critically ill patients). 16 As mentioned previously, ACE2 is expressed in other tissues, such as the liver. 3 Interestingly, hepatocytes do not express the ACE2 receptor as much as bile duct epithelial cells, suggesting that, at least in theory, biliary tract could be more susceptible to SARS-CoV-2-driven injury. However, in the studies conducted so far, no increase in bile duct injury markers, such as gamma-glutamyl transferase and alkaline phosphatase, has been observed. Moreover, SARS-CoV-2 viremia seems to be uncommon, despite severe pneumonia with high viral replication in the lung. The virus has been detected in feces, even several days after clearance on nasopharyngeal swaps. Patients with more advanced liver diseases, including hepatitis B, and those with lower serum albumin levels showed impaired prognosis. A viral translocation from the gut to the liver could allow the virus to reach the liver and promote hepatic injury.