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

Abstract

The novel coronavirus SARS-CoV-2 (coronavirus disease 19, or COVID-19) primarily causes pulmonary injury, but has been implicated to cause hepatic injury, both by serum markers and histologic evaluation. The histologic pattern of injury has not been completely described. Studies quantifying viral load in the liver are lacking. Here we report the clinical and histologic findings related to the liver in 40 patients who died of complications of COVID-19. A subset of liver tissue blocks were subjected to polymerase chain reaction (PCR) for viral ribonucleic acid (RNA). Peak levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were elevated; median ALT peak 68 U/l (normal up to 46 U/l) and median AST peak 102 U/l (normal up to 37 U/l). Macrovesicular steatosis was the most common finding, involving 30 patients (75%). Mild lobular necroinflammation and portal inflammation were present in 20 cases each (50%). Vascular pathology, including sinusoidal microthrombi, was infrequent, seen in six cases (15%). PCR of liver tissue was positive in 11 of 20 patients tested (55%). In conclusion, we found patients dying of COVID-19 had biochemical evidence of hepatitis (of variable severity) and demonstrated histologic findings of macrovesicular steatosis and mild acute hepatitis (lobular necroinflammation) and mild portal inflammation. We also identified viral RNA in a sizeable subset of liver tissue samples.

Correlation of liver-to-spleen ratio, lung CT scores, clinical, and laboratory findings of COVID-19 patients with two consecutive CT scans

“…It has been suggested that hepatic steatosis might develop during the course of COVID-19 [31]. Histopathological examinations of the liver in COVID-19 patients have shown hepatic steatosis, mild lobular and portal inflammation [31,32]. The decrease in L/S in the progressive group on followup that was identified in our study might be attributed to hepatic steatosis.…”

“…It has been suggested that hepatic steatosis might develop during the course of COVID-19 [31]. Histopathological examinations of the liver in COVID-19 patients have shown hepatic steatosis, mild lobular and portal inflammation [31,32].…”

Lipidomic Signatures Align with Inflammatory Patterns and Outcomes in Critical Illness

“…In stark contrast to the early changes in circulating lipids, a subset of lipids (predominantly TAG, DAG, and PE) began to rise in the circulation between 24 and 72h in patients that subsequently exhibited a slow recovery or die. In addition to lipolysis and hypermetabolism, patients with critical illness experience pathologic alterations in liver such as hepatic steatosis [31][32][33][34][35] . Studies in severe burn trauma associate the browning of white adipose tissue with enhanced lipogenesis in liver 36,37 .…”

Pathophysiological mechanisms of liver injury in COVID‐19

“…Cholestatic features such as bile duct proliferation, portal inflammatory infiltrates, and in some cases, canalicular/ductular bile plugs have been reported in post-mortem evaluations on COVID-19 patients. 49,119 The cytokine storm characteristic of the SARS-CoV-2associated viral sepsis 120 may be a major contributing factor, since cytokines like TNF-alpha, IL-1 and IL-6 can induce hepatocellular cholestasis by down-regulating hepatobiliary uptake and excretory systems, 121,122 resembling the pathomechanisms seen in sepsis-induced cholestasis. [121][122][123][124][125] Further studies will have to explore In addition to hepatocellular features, bile duct changes, such as ductular proliferation have been observed in postmortem studies.…”