*4.4. Liver Function Test Abnormalities*

In our case series, the liver function (both transaminases and bilirubin levels) at presentation and during the course of the disease was unremarkable, even in the severe cases. This is in contrast with the literature on immunocompetent patients with COVID-19, in whom liver function test abnormalities are associated with a severe course of the SARS-CoV-2 infection [13]. In a meta-analysis, including 3428 patients from 20 retrospective studies, liver dysfunction was significantly higher in critically ill patients with unfavorable outcomes in COVID-19 [14,15], as could also be observed in other coronaviral diseases (SARS and MERS) [16–18]. Studies show the incidence of liver injury ranging from 58–78%, presenting with elevated transaminases and bilirubin levels [19,20]. Autopsy studies show mild lobular and portal activity along with microvascular stenosis [14,21–23]. In case of hepatic involvement in COVID-19, this can be a direct cytopathic effect such as in hyperinflammation (cytokine storm) and sepsis, or a drug-induced liver injury. Interestingly, cholangiocytes have a higher ACE2 receptor expression, which makes the liver a potential target for SARS-CoV-2 [15]. In the literature, a higher proportion of liver enzyme elevation was observed in patients receiving lopinavir/ritonavir treatment (56.1% vs. 25%) [24], but in our case series none of the LTR received this drug treatment. However, one study in patients with COVID-19 showed liver injury in 10–13% of patients treated with remdesivir [25]. We did not observe this in our cohort (data on evolution of liver enzymes not shown).
