Liver Histopathological Analysis of 24 Postmortem Findings of Patients With COVID-19 in China

Abstract

Although the pathologic investigation of liver injury was observed in a couple of cases in China, the detailed description of liver histopathologic and ultrastructural changes in a relatively larger series of liver tissues from COVID-19 patients is lacking. Samples from the liver were obtained from 24 COVID-19 cases from February 1 to April 1, 2020. Light microscopy showed that all liver sections had different degrees of liver injury manifested as swelling of the hepatocytes, hepatocellular necrosis, steatosis, lobular inflammation, portal inflammation, dilatation of sinusoids, and so on. SARS-CoV-2 induced liver injury might be independent of pre-existing Schistosoma infection or obstructive cholestasis. Patients combined with respiratory failure had more severe hepatocellular necrosis and male patients were more susceptible to liver injury. Although coronavirus particles or viral inclusions were not detected in the liver tissues for all cases, vacuolar degenerations in hepatocytes, edematous of mitochondria with the disruption of cristae, and expansions of the endoplasmic reticulum were observed. In conclusion, pathologic changes of liver tissues provide us a further understanding of liver injury in COVID-19 patients. Changes in the liver seem to be related to the underlying diseases/conditions.

COVID-19 and liver disease

“…Besides macrovesicular and microvesicular steatosis, microthrombotic pathology dominated in the liver accompanied by activation of intrahepatic stem cell compartment and features of aberrant regeneration 24. Not all liver histopathological studies showed detectable virus particles in the liver 25. In this autopsy study, 42% of patients (n=24) exhibited evidence of severe hepatic necrosis, obviously a key histological feature besides macrovesicular/microvesicular steatosis, data which are also supported by a recent systematic review 26.…”

COVID-19: gastrointestinal and hepatobiliary manifestations

“…Immunohistochemistry for SARS-CoV-2 highlighted portal macrophages in 5 of 17 cases in the study by Zhao and other. [ 69 ] By electron microscopy, viral particles were not identified in one series of 24 cases, [ 70 ] but others reported virion-like particles in their cases. [ 69 ] In rare reports of patients with liver injury presumably due to COVID-19, some biopsies have demonstrated viral antigens by ISH [ 43 , 71 ] as well as electron microscopy, [ 43 ] suggesting the SARS-CoV-2 can directly infect the liver.…”

Liver, NAFLD and COVID-19

“…Several studies have also reported important vascular changes including vascular thrombosis and periportal herniation of the portal vein (24,25). On cellular level, hepatocyte ballooning, dilatation of the sinusoids and Kupffer cell proliferation/hyperplasia have been commonly observed (24,25).…”

“…Several studies have reported a wide variety of pathologic findings in liver histology of patients with COVID-19 [24,25]. The most fre- quent is the presence of micro-and macrovesicular steatosis.…”

“…On the other hand, viral RNA was detected with PCR in 11 out of 20 autopsy livers, but PCR positivity did not correlate with any histologic finding 41 . Chu et al reported that neither electron microscopy nor gene expression analysis could detect coronavirus particles, viral inclusions, or viral RNA in 24 liver autopsy samples from patients who died from COVID-19, despite the fact that profound signs of liver damage both on a tissue (steatosis, inflammation, necrosis, dilatation of sinusoids) and cellular level (swelling mitochondria with cristae, expansions of endoplasmic reticulum) were present 25 . Although comparisons of liver histology after COVID-19 infection between NAFLD versus controls have not been performed, a recent study reported histologic differences in fatal COVID-19 between patients with versus without alcohol use disorder (AUD).…”