This is the author manuscript accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as

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.

Objective: Increased mortality risk because of severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) infection in adults with native liver disease (LD) and liver transplant (LT) is associated with advanced age and comorbid conditions. We aim to report outcomes for children with LD and LT enrolled in the NASPGHAN/SPLIT SARS-CoV2 registry. Methods: In this multicenter observational cohort study, we collected data from 91 patients <21 years (LD 44, LT 47) with laboratory-confirmed SARS-CoV2 infection between April 21 and September 17, 2020. Results: Patients with LD were more likely to require admission (70% vs 43% LT, P = 0.007) and pediatric intensive care unit (PICU) management (32% vs 4% LT, P = 0.001). Seven LD patients required mechanical ventilation (MV) and 2 patients died; no patients in the LT cohort died or required MV. Four LD patients presented in pediatric acute liver failure (PALF), 2 with concurrent multisystem inflammatory syndrome in children (MIS-C); all recovered without LT. Two LD patients had MIS-C alone and 1 patient died. Bivariable logistic-regression analysis found that patients with nonalcoholic fatty LD (NAFLD) (odds ratio [OR] 5.6, P = 0.02) and LD (OR 6.1, P = 0.01, vs LT) had higher odds of severe disease (PICU, vasopressor support, MV, renal replacement therapy or death). Conclusions: Although not directly comparable, LT recipients had lower odds of severe SARS-CoV2 infection (vs LD), despite immunosuppression burden. NAFLD patients reported to the registry had higher odds of severe SARS-CoV2 disease. Future controlled studies are needed to evaluate effective treatments and further stratify LD and LT patients with SARS-CoV2 infection.