High Prevalence of Pre-Existing Liver Abnormalities Identified Via Autopsies in COVID-19: Identification of a New Silent Risk Factor?

Abstract

A high prevalence of hepatic pathology (in 17 of 19 cases) was reported in post-mortem (PM) examinations of COVID-19 patients, undertaken between March 2020 and February 2021 by a single autopsy pathologist in two English Coronial jurisdictions. The patients in our cohort demonstrated high levels of recognised COVID-19 risk factors, including hypertension (8/16, 50%), type 2 diabetes mellitus (8/16, 50%) and evidence of arteriopathy 6/16 (38%). Hepatic abnormalities included steatosis (12/19; 63%), moderate to severe venous congestion (5/19; 26%) and cirrhosis (4/19; 21%). A subsequent literature review indicated a significantly increased prevalence of steatosis (49%), venous congestion (34%) and cirrhosis (9.3%) in COVID-19 PM cases, compared with a pre-pandemic PM cohort (33%, 16%, and 2.6%, respectively), likely reflecting an increased mortality risk in SARS-CoV-2 infection for patients with pre-existing liver disease. To corroborate this observation, we retrospectively analysed the admission liver function test (LFT) results of 276 consecutive, anonymised COVID-19 hospital patients in our centre, for whom outcome data were available. Of these patients, 236 (85.5%) had significantly reduced albumin levels at the time of admission to hospital, which was likely indicative of pre-existing chronic liver or renal disease. There was a strong correlation between patient outcome (length of hospital admission or death) and abnormal albumin at the time of hospital admission (p = 0.000012). We discuss potential mechanisms by which our observations of hepatic dysfunction are linked to a risk of COVID-19 mortality, speculating on the importance of recently identified anti-interferon antibodies.

COVID-19, Possible Hepatic Pathways and Alcohol Abuse—What Do We Know up to 2023?

“…Even though the findings of abdominal ultrasound examination are usually irrelevant in patients with normal results of liver function tests, in the case of significant increase in aminotransferases, vascular disorders and cholestatic abnormalities can be observed and related to a higher rate of mortality [161,162]. The data on post-mortem assessment of nineteen COVID-19 individuals without a previous known history concerning liver disorders revealed the presence of hepatic abnormalities in seventeen of them (89%) [163]. According to available literature, it is hard to generalize the main type of cytopathic effect of SARS-CoV-2 exerted on the liver.…”

Liver histopathological changes and COVID-19: What does literature have to tell us?

“…In fact, during the SARS-CoV-2 infection process, studies show an intense inflammatory process in the portal and lobular regions [5] , [6] , [7] , [8] ( Figure 2 ). It is important to point out that, in an acute injury, aggregates of macrophages and lymphocytes are observed in the hepatic lobe, as well as a chronic infiltrate of inflammatory cells close to the portal regions.…”

“…According to the literature, the most common histopathological changes associated with SARS-CoV-2 were hepatic steatosis (HS), thrombosis or/and portal and periportal inflammatory infiltrate, Kupffer cell hyperstimulation and cholestasis [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] . We summarize the main histopathological findings of COVID-19 in the liver in Figure 1 , Figure 2 .…”

“…Regarding cell proliferation, two findings were relevant in the literature. The first one concerns the proliferation of Kupffer cells, whose function is to resolve the inflammatory process and wound healing [ 1 , 6 ]. Such cells act in the mononuclear phagocytic system and are central to the hepatic and systemic response to pathogens [6] .…”

“…The first one concerns the proliferation of Kupffer cells, whose function is to resolve the inflammatory process and wound healing [ 1 , 6 ]. Such cells act in the mononuclear phagocytic system and are central to the hepatic and systemic response to pathogens [6] . In this context, regarding the changes triggered by the new coronavirus (SARS-CoV-2) in the liver, the result of a study with 11 autopsies showed that Kupffer cells were activated in all patients, having a nodular proliferation of 70% [7] .…”