Liver injury in severe COVID-19 disease - Need a closer look!

Dear Editor:

We read with great interest the study by Chew et al concluding that liver test abnormalities associated with COVID-19 per se do not lead to liver insufficiency or death. Whereas, COVID-19-related ischemic, hypercoagulable, and hyperinflammatory disease states are significant predictors of death. Some of the issues need further consideration.

First, mortality in COVID-19 is determined by disease severity at hospital admission and standards of intensive care unit support. Ischemia, hyperinflammation, and hypercoagulability are hallmarks of severe COVID-19 disease. Previous studies have shown correlation of significant liver injury with severity of COVID-19. , Moreover, these patients often require use of potentially hepatotoxic drugs, such as tocilizumab, which might contribute to liver injury. Significant liver injury more often suggests severe COVID-19 disease and all these factors are likely correlated. The acute liver injury in the presence of COVID-19 is multifactorial and in the absence of liver biopsy, it is often difficult to determine the actual cause.

Second, in patients with significant liver injury, mortality is also determined by the presence and severity of preexisting liver disease. In the current study, <5% of patients had liver cirrhosis. Patients with liver cirrhosis present unique challenges. Immune dysfunction in cirrhosis led to increased susceptibility to infection and aberrant inflammatory response during infection, collectively known as cirrhosis-associated immune dysfunction. The current therapeutic armamentarium to treat severe COVID-19 in patients with severe liver disease is limited. Most of the specific drugs for moderate to severe COVID-19 disease including remdesivir, lopinavir–ritonavir, tocilizumab, and high-dose dexamethasone are contraindicated in the presence of severe liver disease. Moreover, the data on clinical outcomes for these difficult-to-treat patients are limited. In the SECURE-Cirrhosis and COVID-Hep registries, hepatic decompensation events and mortality were more frequent with increasing severity of liver disease. Severe COVID-19 might also precipitate acute-on-chronic liver failure.

Third, in the current study, the diagnosis of ischemic liver injury was considered only after 2 days of vasopressor support. At this stage, it is often too late and patients have very high mortality.

In summary, the clinical relevance of this important study on liver injury and COVID-19 disease could have been enhanced by accounting for the previously mentioned factors.