Liver histopathology in severe COVID 19 respiratory failure is suggestive of vascular alterations

Abstract

SARS2‐CoV‐2 breakout in Italy caused a huge number of severely ill patients with a serious increase in mortality. Although lungs seem to be the main target of the infection, very few information are available about liver involvement, possibly evocating a systemic disease. Post‐mortem wedge liver biopsies from 48 patients died from severe pulmonary COVID‐19 disease with respiratory failure were collected from two main hospitals in northern Italy. No patient had clinical symptoms of liver disease or signs of liver failure before and during hospitalization; for each of them liver function tests were available. All liver samples showed minimal inflammation features. Histological pictures compatible with vascular alterations were observed, characterized by increase in number of portal vein branches associated with lumen massive dilatation, partial or complete luminal thrombosis of portal and sinusoidal vessels, fibrosis of portal tract, focally markedly enlarged and fibrotic. SARS‐CoV‐2 was found in 15 of 22 samples tested by in situ hybridization method. Our preliminary results confirm the clinical impression that liver failure is not a main concern and this organ is not the target of significant inflammatory damage. Histopathological findings are highly suggestive for marked derangement of intrahepatic blood vessel network secondary to systemic changes induced by virus that could target not only lung parenchyma but also cardiovascular system, coagulation cascade and endothelial layer of blood vessels. It still remains unclear if the mentioned changes are directly related to virus infection or if SARS‐CoV‐2 triggers a series of reactions leading to striking vascular alterations.

Hepatic pathology in patients dying of COVID-19: a series of 40 cases including clinical, histologic, and virologic data

“…While we cannot exclude these findings being meaningful (if they are present throughout the entire liver), we do not believe that vascular injury is the major mechanism of injury in the liver in COVID-19 patients. This contrasts with a case series from Italy, which describes vascular pathology not frequently encountered in our cohort [18]. The "thrombotic bodies" we observed are likely the same "microthrombi" identified in multiple organs in a recent series of seven autopsies [19].…”

Correlation analysis of coagulation dysfunction and liver damage in patients with novel coronavirus pneumonia: a single-center, retrospective, observational study

“…Recent research has shown that the hypercoagulable state of COVID-19 patients alters intrahepatic vascular structures and causes a variable degree of luminal thrombosis. This may add to other mechanisms of liver damage in COVID-19 patients (19).…”

“…Several studies have shown that, in addition to coagulation dysfunction, COVID-19 patients will have different degrees of liver damage as well. The pathogenesis of liver damage complicated by COVID- 19 is not yet clear; however, current mainstream views on the mechanism of liver injury include: (1) Angiotensin-converting enzyme 2 (ACE2) mediates SARS-CoV-2 invasion of target cells. Bile duct epithelial cells highly express ACE2, and its expression level is similar to alveolar type II cells, which is the main target cell type of SARS-CoV-2 in the lung.…”

“…The S protein on the surface of SARS-CoV-2 binds to angiotensin-converting enzyme II (ACE2), which leads SARS-CoV-2 to enter the host cell (2,3). Some researchers (4)(5)(6) have reported that patients with COVID- 19 have varying degrees of coagulopathy and liver damage as the disease progresses. The liver is closely related to the synthesis of coagulation factors, which means that when the liver is damaged, it will directly affect the coagulation function.…”

A review on how to do hematology consults during COVID-19 pandemic

“…The severity of this phenomenon correlates with the severity of the critical illness of the patients. Postmortem series have confirmed evidence of multi-organ and disseminated microvascular thrombosis in various organs [ 19 , 20 ]. This has served as a platform for a few ongoing clinical trials to try prophylactic high-intensity prophylaxis in critically ill patients with COVID-19 with no known thrombosis.…”