COVID-19 and liver disease: mechanistic and clinical perspectives

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.
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.
Key points Patients with cirrhosis have high rates of hepatic decompensation, acute-on-chronic liver failure and death from respiratory failure following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and should be prioritized for coronavirus disease 2019 (COVID-19) vaccination.The possible pathogenic mechanisms linking cirrhosis with severe COVID-19 lung disease include increased systemic inflammation, cirrhosis-associated immune dysfunction, coagulopathy and intestinal dysbiosis.Abnormal liver biochemistry values are common in patients with COVID-19; both the prognostic significance of these derangements and whether they are directly attributable to hepatic SARS-CoV-2 infection remain uncertain.Expression profiles of SARS-CoV-2 entry receptors vary across different in vitro and in vivo liver models; however, evidence of specific viral hepatotropism is limited.Liver transplant recipients do not appear to have an increased risk of mortality following SARS-CoV-2 infection compared with the matched general population.The pandemic has been associated with increased alcohol consumption, unhealthy eating habits, and interruptions to hepatology services, which might lead to an upward trend in liver disease incidence and severity.