Direct or Collateral Liver Damage in SARS-CoV-2–Infected Patients

Abstract

Liver injury can result from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with more than one-third of COVID-19 patients exhibiting elevated liver enzymes. Microvesicular steatosis, inflammation, vascular congestion, and thrombosis in the liver have been described in autopsy samples from COVID-19 patients. Several factors, including direct cytopathic effect of the virus, immune-mediated collateral damage, or an exacerbation of preexisting liver disease may contribute to liver pathology in COVID-19. Due to its immunological functions, the liver is an organ likely to participate in the viral response against SARS-CoV-2 and this may predispose it to injury. A better understanding of the mechanism contributing to liver injury is needed to develop and implement early measures to prevent serious liver damage in patients suffering from COVID-19. This review summarizes current reports of SARS-CoV-2 with an emphasis on how direct infection and subsequent severe inflammatory response may contribute to liver injury in patients with and without preexisting liver disease.

COVID-19 Mid-term Impact on Hepatocellular Carcinoma in Patients With Hepatitis C Chronic Infection

“…Moreover, the liver's dual blood supply facilitates antigen arrival from the gut (26). Therefore, it is expected that the liver would take part in the viral response against SARS-CoV-2 since the virus binds to the angiotensin-converting enzyme 2 (ACE2) receptor, which is found mainly in cholangiocytes, but also in the vascular endothelium and perivenular hepatocytes (27). Within the normal hepatocytes, ACE2 expression is typically low, but in the cirrhotic liver increased expression is often observed within the cirrhotic nodules (27).…”

“…Therefore, it is expected that the liver would take part in the viral response against SARS-CoV-2 since the virus binds to the angiotensin-converting enzyme 2 (ACE2) receptor, which is found mainly in cholangiocytes, but also in the vascular endothelium and perivenular hepatocytes (27). Within the normal hepatocytes, ACE2 expression is typically low, but in the cirrhotic liver increased expression is often observed within the cirrhotic nodules (27). Moreover, hypoxia results in an upregulation of ACE2 receptor expression on hepatocytes; a study by Paizis et al suggests that the expression rate increases with the duration of hypoxia (28).…”

Mesenchymal stromal cell secretome in liver failure: Perspectives on COVID-19 infection treatment

“…The hypoxic state associated with COVID-19 can induce ischemic/hypoxic liver injury[ 87 - 89 ]. Considering that COVID-19 patients suffer from severe hypoxia, with the induction of ACE2 receptor expression on hepatocytes[ 96 ], a direct infection of hepatocytes by SARS-CoV-2 in hypoxic conditions has been suggested[ 25 ]. Liver injury can also be drug-induced.…”

“…It has been hypothesized that MSC-based therapy for COVID-19 patients can prevent the development of a cytokine storm by activating the immune system and promoting organ repair[ 24 , 25 ]. Intravenously injected MSCs reach the lungs, where they engraft and secrete a variety of soluble factors including anti-inflammatory factors, angiogenic factors, and EVs[ 26 , 27 ].…”

Increased Hepatic Expression of SARS-CoV-2 Entry Points and Proinflammatory Cytokines in Cirrhosis

“…It has been postulated that this could be multifactorial, including an immune-mediated inflammatory response. 10 To investigate if cirrhotic patients, besides the wellknown underlying systemic inflammation, 3 also have an underlying intrahepatic inflammation, we measured the mRNA hepatic expression of 3 well-known cytokines and chemokines associated with inflammation and recruitment of macrophages/neutrophils, IL-6, IL-8, and MCP-1. 4,5 .…”