COVID‐19 and the liver – Lessons learned

Abstract

Liver involvement, indicated by elevated liver function test results, is common in hospitalized patients with coronavirus disease 2019 (COVID‐19) and has been linked to disease severity and outcome. A dual pattern of elevated liver function tests can be observed especially in patients with severe or critical COVID‐19, characterized by an increase in aminotransferases early in the course of this disease, followed by an increase in cholestasis‐associated biochemistry markers at later stages. This dual pattern is associated with inflammatory response markers and poor outcome. Current notions on the mechanisms of liver injury in COVID‐19 include direct cytopathic effects of the virus on hepatocytes and cholangiocytes, ischemic and hypoxic liver damage, drug‐induced liver injury, activation of hepatic immune cells by excess cytokine production and exacerbation of pre‐existing liver disease. Patients with obesity‐related non‐alcoholic fatty liver disease and, in particular, patients with cirrhosis are at high risk of liver injury and a fatal outcome from COVID‐19. In contrast, individuals receiving stable immunosuppressive medication for autoimmune liver diseases or during long‐term follow‐up after liver transplantation do not have a higher case‐to‐infection ratio and have a fairly favourable outcome. The present review describes the epidemiology, characteristics and potential pathological mechanisms of COVID‐19‐related liver injury. Moreover, the influence of pre‐existing liver disease on the susceptibility and severity of liver injury in COVID‐19 are discussed.

Hepatocellular injury and the mortality risk among patients with COVID-19: A retrospective cohort study

“…On the other hand, serum ALT, bilirubin and albumin levels did not alter mortality after correction for age, sex and other relevant clinical factors. Our findings are consistent with recent reports investigating progressive liver injury and the risk of mortality among patients with COVID-19 where AST levels but not ALT levels at admission were a strong predictor of mortality[ 9 - 11 ].…”

“…Furthermore, SARS-CoV-2 may induce endothelial cell injury in the hepatic microcirculation and promote portal or sinusoidal microthrombosis. In individuals with ischaemic liver injury (due to microthrombosis), serum AST levels peak before ALT levels, a pattern that was observed in our cohort[ 9 , 11 , 13 ].…”

“…Moreover, hyperinflammatory syndrome can induce disseminated intravascular coagulation with ischaemic hepatocellular injury by microvascular thrombosis in the hepatic microcirculation. In addition, direct endothelial cell damage in the hepatic microcirculation induced by SARS-CoV-2 may promote microvascular thrombosis and ischaemic liver injury[ 11 ].…”

New Onset of Hepatic Steatosis Post-Severe Multisystem Inflammatory Syndrome in Children (MIS-C): A Case Report

“…COVID-19-associated liver injury is defined as any liver damage occurring during disease course and treatment of COVID-19 patients, with or without pre-existing liver disease [ 13 ] and typically leads to a temporary moderate elevation of liver tests without significant hepatic synthetic function impairment. Patients with SARS-CoV-2 infection and elevated ALT are at risk of a more severe disease course including longer hospitalization and ICU stays [ 14 ]. Patients with greater elevations in serum ALT levels often have high levels of CRP, which is synthesized by the liver, D- dimer, ferritin and IL-6.…”

Biliary atresia in a neonate with a history of COVID-19: A case report

“…Although the evidence for COVID-19 associated liver injury is increasing, the cause is unclear [19] . Evidence exists to support direct injury by the virus on liver cells, ischemic damage, drug induced insult, and exacerbation of prior liver injury [20] .…”