4.7 Review

COVID-19 and liver disease: mechanistic and clinical perspectives

Journal

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
Volume 18, Issue 5, Pages 348-364

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41575-021-00426-4

Keywords

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Funding

  1. European Association for Study of the Liver (EASL) [2020RG03]
  2. Wellcome Trust Clinical Research Fellowship [102176/B/13/Z]
  3. National Institutes of Health [T32 DK007634]
  4. Gilead Sciences
  5. Medical Research Foundation [MRF-169-0001-F-STAM-C0826]
  6. Oxford National Institute for Health Research (NIHR) Biomedical Research Centre

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This article provides insights into the mechanistic and clinical aspects of COVID-19 in the context of liver disease, discussing viral hepatotropism, differential expression of viral receptors on liver cell types, and liver histology features in COVID-19 patients. It also highlights the impact of COVID-19 on patients with pre-existing chronic liver disease and the potential strategies for managing these patients, including vaccination.
This Review provides mechanistic and clinical insights into COVID-19 in the context of liver disease, discussing the potential underlying biology and clinical features of SARS-CoV-2 infection in patients with pre-existing liver conditions. The management of these patients is also discussed, including SARS-CoV-2 vaccination strategies. Our understanding of the hepatic consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its resultant coronavirus disease 2019 (COVID-19) has evolved rapidly since the onset of the pandemic. In this Review, we discuss the hepatotropism of SARS-CoV-2, including the differential expression of viral receptors on liver cell types, and we describe the liver histology features present in patients with COVID-19. We also provide an overview of the pattern and relevance of abnormal liver biochemistry during COVID-19 and present the possible underlying direct and indirect mechanisms for liver injury. Furthermore, large international cohorts have been able to characterize the disease course of COVID-19 in patients with pre-existing chronic liver disease. Patients with cirrhosis have particularly high rates of hepatic decompensation and death following SARS-CoV-2 infection and we outline hypotheses to explain these findings, including the possible role of cirrhosis-associated immune dysfunction. This finding contrasts with outcome data in pharmacologically immunosuppressed patients after liver transplantation who seem to have comparatively better outcomes from COVID-19 than those with advanced liver disease. Finally, we discuss the approach to SARS-CoV-2 vaccination in patients with cirrhosis and after liver transplantation and predict how changes in social behaviours and clinical care pathways during the pandemic might lead to increased liver disease incidence and severity.

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