Open AccessCorrelation Between Clinical and Pathological Findings of Liver Injury in 27 Patients With Lethal COVID‐19 Infections in Brazil
Author(s) -
Santana Monique Freire,
Guerra Mateus T.,
Hundt Melanie A.,
Ciarleglio Maria M.,
Pinto Rebecca Augusta de Araújo,
Dutra Bruna Guimarães,
Xavier Mariana Simão,
Lacerda Marcus Vinicius Guimarães,
Ferreira Anderson Jose,
Wanderley David Campos,
Borges do Nascimento Israel Júnior,
Araújo Roberto Ferreira de Almeida,
Pinheiro Sérgio Veloso Brant,
Araújo Stanley de Almeida,
Leite M. Fatima,
Ferreira Luiz Carlos de Lima,
Nathanson Michael H.,
Vieira Teixeira Vidigal Paula
Publication year - 2022
Publication title -
hepatology communications
Language(s) - English
Resource type - Journals
ISSN - 2471-254X
DOI - 10.1002/hep4.1820
Subject(s) - medicine , histopathology , liver injury , pathology , gastroenterology , pathological , aspartate transaminase , alanine transaminase , steatosis , coronavirus , fatty liver , lung , covid-19 , disease , biology , alkaline phosphatase , enzyme , biochemistry , infectious disease (medical specialty)
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.