Pathological findings in the postmortem liver of patients with coronavirus disease 2019 (COVID-19)

Abstract

Introduction Although COVID-19 is transmitted via respiratory droplets, there are multiple gastrointestinal and hepatic manifestations of the disease, including abnormal liver-associated enzymes. However, there are not many published articles on the pathological findings in the liver of COVID-19 patients. Methods We collected the clinical data from 17 autopsy cases of COVID-19 patients including age, sex, BMI, liver function test (ALT, AST, ALP, direct bilirubin and total bilirubin), D-dimer and anticoagulation treatment. We examined histopathologic findings in postmortem hepatic tissue, immunohistochemical (IHC) staining with antibody against COVID spike protein, CD68 and CD61, and electron microscopy. We counted the number of megakaryocytes in liver sections from these COVID-19 positive cases. Results Abnormal liver-associated enzymes were observed in 12/17 cases of COVID-19 infection. With the exception of three cases that had not been tested for D-dimer, all 14 patients’ D-dimer levels were increased, including the cases that received varied doses of anticoagulation treatment. Microscopically, the major findings were widespread platelet-fibrin microthrombi, steatosis, histiocytic hyperplasia in the portal tract, mild lobular inflammation, ischemic-type hepatic necrosis and zone 3 hemorrhage. Rare megakaryocytes were found in sinusoids. COVID IHC demonstrates positive staining of the histiocytes in the portal tract. Under electron microscopy, histiocyte proliferation is present in the portal tract containing lipid droplets, lysosomes, dilated ribosomal endoplasmic reticulum (RER), micro-vesicular bodies and coronavirus. Conclusions The characteristic findings in COVID-19 patients’ liver include numerous amounts of platelet-fibrin microthrombi as well as various degrees of steatosis and histiocytic hyperplasia in the portal tract. Possible mechanisms are also discussed.

Microvascular Angiopathic Consequences of COVID-19

“…Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) has confirmed the presence of SARS-CoV genome in hepatic tissue, suggesting that COVID-19 may be directly binding to the liver microvasculature and causing hepatic complications ( 73 , 74 ). Post-mortem studies of patients who died following COVID-19 infections demonstrated platelet-fibrin micro-thrombi within the hepatic microvasculature, various degrees of steatosis and portal histiocytic hyperplasia, and hepatic tissue ischemic necrosis ( 75 ). Another study reported patchy necrosis of the liver as well as wide infiltration by small lymphocytes ( 76 ).…”

Pathophysiology of infection with SARS‐CoV‐2—What is known and what remains a mystery

“…Furthermore, use of liver organoids that have been derived from human pluripotential stem cells are able to support virus replication. 149 A number of autopsy studies detailing the liver pathology in COVID-19 have been reported in the United States, 142,150 Belgium 103,146 and Netherlands, 103 in which a common feature is steatosis (often microvesicular), platelet fibrin microthrombi, lobular inflammation, Zone 3 haemorrhage and ischaemic type hepatic necrosis. The challenge with these finding is that hepatic pathologies such as steatosis can be seen in patients who have a high risk of developing severe disease, that is, diabetes, obesity and patients with cardiovascular disease.…”

Inflammatory Response in COVID-19 Patients Resulting from the Interaction of the Inflammasome and SARS-CoV-2

“…In some cases, elevated interstitial CD68 + macrophage numbers were reported [ 47 ]. Moreover, patients with COVID-19 showed distinct hepatic symptoms [ 48 ]. Aberrant hepatic enzymes, hyperplasia, platelet-fibrin microthrombi, lobular inflammation, ischaemic hepatic necrosis, and steatosis were observed in the post-mortem livers of patients with COVID-19 [ 48 ].…”

“…Moreover, patients with COVID-19 showed distinct hepatic symptoms [ 48 ]. Aberrant hepatic enzymes, hyperplasia, platelet-fibrin microthrombi, lobular inflammation, ischaemic hepatic necrosis, and steatosis were observed in the post-mortem livers of patients with COVID-19 [ 48 ]. One of the major causes of death of patients with COVID-19 was respiratory failure [ 49 ].…”