Hepatology Communications (Feb 2022)

Correlation Between Clinical and Pathological Findings of Liver Injury in 27 Patients With Lethal COVID‐19 Infections in Brazil

  • Monique Freire Santana,
  • Mateus T. Guerra,
  • Melanie A. Hundt,
  • Maria M. Ciarleglio,
  • Rebecca Augusta de Araújo Pinto,
  • Bruna Guimarães Dutra,
  • Mariana Simão Xavier,
  • Marcus Vinicius Guimarães Lacerda,
  • Anderson Jose Ferreira,
  • David Campos Wanderley,
  • Israel Júnior Borges do Nascimento,
  • Roberto Ferreira de Almeida Araújo,
  • Sérgio Veloso Brant Pinheiro,
  • Stanley de Almeida Araújo,
  • M. Fatima Leite,
  • Luiz Carlos de Lima Ferreira,
  • Michael H. Nathanson,
  • Paula Vieira Teixeira Vidigal

DOI
https://doi.org/10.1002/hep4.1820
Journal volume & issue
Vol. 6, no. 2
pp. 270 – 280

Abstract

Read online

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.