Discussion
In our study, patients with elevated baseline LFTs had a higher chance of meeting the composite endpoint of death or mechanical ventilation during hospitalization. To the best of our knowledge, this is the first study to document the relation between abnormal baseline LFTs and the susceptibility to a more severe COVID-19 course during hospitalization.
Most of the studies that looked into the association between COVID-19 and the liver have either described the pattern of liver injury due to COVID-19 or the clinical characteristics and outcomes of patients presenting with hepatic dysfunction due to SARS-COV-22,4,10,11. The ubiquitous distribution of SARS-COV-2 receptor for viral entry, ACE2, on Cholangiocytes naturally points towards a hepatic injury being a common systemic manifestation of extrapulmonary COVID-19 infection 12. Possible mechanisms that may potentially underlie this association include immune-mediated damage as a result of the severe inflammatory response commonly referred to as “the cytokine storm” 13 , direct hepatotoxicity due to viral replication in hepatic cells, anoxic damage (hypoxic hepatitis) that may accompany respiratory failure, Drug-induced liver injury (DILI) and the reactivation of a pre-existing liver disease 14-16.
Given the heterogenous nature of different liver diseases, the outcomes of patients with pre-existing liver disease that become infected with COVID-19 may vary significantly depending on the underlying liver disease, presumably due to a modifying element of immunosuppression on the inflammatory response that predominates the illness. As the host inflammatory response appears to be the main driver of pulmonary damage in this infection,
a useful framework to characterize this association would be to divide the pre-existing liver diseases into 2 categories; those with an attenuated inflammatory response and those with pronounced inflammatory responses. Examples of the former category include patients with autoimmune hepatitis, malignancies, and liver transplant recipients where preliminary evidence suggests that these patients might not be at an increased risk of severe complications compared to the general population 17. On the other hand, patients with chronic liver disease that are associated with hyperinflammatory states such as non-alcoholic fatty liver disease (NAFLD) and cirrhosis appear to be at an increased risk of severe COVID-19 course18,19. NAFLD patients in particular appear to be at an increased risk for developing hepatic injury during hospitalization due to the deleterious interplay of chronically active inflammatory pathways and the acute cytokine storm that accompanies COVID-1920. Often referred to as the hepatic manifestation of metabolic syndrome, NAFLD was shown to be an independent risk factor for severe COVID-19 infection even in the absence of other constituents of metabolic syndrome 21.
Our study has several limitations; namely the inherent limitations of relatively small sample size and retrospective, single-center design but it highlights a clinically important association and emphasizes the unmet need for larger scale studies to further characterize the relation between liver disease and COVID-19 clinical course. The exact cause of pre‐existing liver conditions has not been outlined in the majority of included subjects, which makes it difficult to analyze the impact of COVID‐19 on the different etiologies of pre-existing liver diseases.
No correlation was made between the degree of hepatic dysfunction with inflammatory markers or radiological findings during hospitalization, which could have allowed for a better understanding of the association between abnormal LFTs and MV or mortality.
Finally, the high prevalence of hyperlipidemia and obesity in our cohort may have contributed to an over-estimation of NAFLD impact on patients’ outcomes while underestimating other pre-existing liver diseases impact, although this is representative of larger COVID-19 patient cohorts where obesity and other metabolic syndrome appear frequently among the risk factors and are thought to be harbingers of adverse clinical outcomes.
In conclusion, patients known to have a baseline LFTs abnormality appear to be at an increased risk for death or mechanical ventilation during hospitalization with COVID-19 infection. Further large scale preferably prospective studies are urgently needed to characterize this clinically important association.