Correlation Between Clinical and Pathological Findings of Liver Injury in 27 Patients With Lethal COVID-19 Infections in Brazil.
Monique Freire SantanaMateus T GuerraMelanie A HundtMaria M CiarleglioRebecca Augusta de Araújo PintoBruna Guimarães DutraMariana Simão XavierMarcus Vinicius Guimarães LacerdaAnderson Jose FerreiraDavid Campos WanderleyIsrael Júnior Borges do NascimentoRoberto Ferreira de Almeida AraújoSérgio Veloso Brant PinheiroStanley de Almeida AraújoM Fatima LeiteLuiz Carlos de Lima FerreiraMichael H NathansonPaula Vieira Teixeira VidigalPublished in: Hepatology communications (2021)
Liver test abnormalities are frequently observed in patients with coronavirus disease 2019 (COVID-19) and are associated with worse prognosis. However, information is limited about pathological changes in the liver in this infection, so the mechanism of liver injury is unclear. Here we describe liver histopathology and clinical correlates of 27 patients who died of COVID-19 in Manaus, Brazil. There was a high prevalence of liver injury (elevated alanine aminotransferase and aspartate aminotransferase in 44% and 48% of patients, respectively) in these patients. Histological analysis showed sinusoidal congestion and ischemic necrosis in more than 85% of the cases, but these appeared to be secondary to systemic rather than intrahepatic thrombotic events, as only 14% and 22% of samples were positive for CD61 (marker of platelet activation) and C4d (activated complement factor), respectively. Furthermore, the extent of these vascular findings did not correlate with the extent of transaminase elevations. Steatosis was present in 63% of patients, and portal inflammation was present in 52%. In most cases, hepatocytes expressed angiotensin-converting enzyme 2 (ACE2), which is responsible for binding and entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), even though this ectoenzyme was minimally expressed on hepatocytes in normal controls. However, SARS-CoV-2 staining was not observed. Most hepatocytes also expressed inositol 1,4,5-triphosphate receptor 3 (ITPR3), a calcium channel that becomes expressed in acute liver injury. Conclusion: The hepatocellular injury that commonly occurs in patients with severe COVID-19 is not due to the vascular events that contribute to pulmonary or cardiac damage. However, new expression of ACE2 and ITPR3 with concomitant inflammation and steatosis suggests that liver injury may result from inflammation, metabolic abnormalities, and perhaps direct viral injury.
Keyphrases
- liver injury
- drug induced
- sars cov
- coronavirus disease
- respiratory syndrome coronavirus
- end stage renal disease
- angiotensin converting enzyme
- ejection fraction
- oxidative stress
- newly diagnosed
- angiotensin ii
- peritoneal dialysis
- poor prognosis
- prognostic factors
- adipose tissue
- left ventricular
- type diabetes
- patient reported outcomes
- subarachnoid hemorrhage
- heart failure
- long non coding rna
- cerebral ischemia