Liver involvement in children with SARS-COV-2 infection: Two distinct clinical phenotypes caused by the same virus

Background and Aims: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) associated acute liver injury (ALI) has been linked to poor outcomes in adults. Here we compare characteristics in children with elevated ALT (E-ALT) in two distinct manifestations of the infection, multisystem inflammatory syndrome-children (MIS-C) and coronavirus disease 2019 (COVID-19). Methods: This is a retrospective study of patients ≤21 years of age with positive for SARS-CoV-2 PCR. E-ALT was defined as alanine aminotransferase (ALT) > 40 U/L. Bivariate analysis and multivariable logistic regression were obtained to describe differences in children with and without E-ALT in COVID-19 and MIS-C. Results: E-ALT was detected in 36% of the 291 patients; 31% with COVID-19, and 51% with MIS-C. E-ALT in COVID-19 was associated with obesity (P <.001), immunocompromised status (P =.04), and chronic liver disease (P =.01). In the regression models, E-ALT in COVID-19 was associated with higher c-reactive protein (OR 1.08, P =.01) after adjusting for common independent predictors. Children with E-ALT and MIS-C were more often boys (P =.001), Hispanic (P =.04), or Black (P <.001). In MIS-C, male gender (OR 5.3, P =.02) and Black race (OR 4.4, P =.04) were associated with increased odds of E-ALT. Children with E-ALT in both cohorts had significantly higher multiorgan dysfunction, longer hospitalization, and ICU stay. Children with MIS-C had 2.3-fold increased risk of E-ALT compared to COVID-19. No association was found between E-ALT and mortality. Conclusion: E-ALT with SARS-CoV-2 presents as elevated transaminases without hepatic synthetic dysfunction. Patients with either manifestation of SARS-CoV-2 infection and E-ALT experienced more severe disease.