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.