Liver Involvement in Children With SARS-COV-2 Infection

Two Distinct Clinical Phenotypes Caused by the Same Virus

Adriana Perez MD; Amanda Cantor MD; Bryan Rudolph MD, MPH; Jonathan Miller MD; Debora Kogan-Liberman MD; Qi Gao PhD; Bernardo Da Silva; Kara G. Margolis MD; Nadia Ovchinsky MD, MBA; Mercedes Martinez MD

Disclosures

Liver International. 2021;41(9):2068-2075. 

In This Article

Abstract and Introduction

Abstract

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.

Introduction

The clinical manifestations of severe acute respiratory syndrome (SARS)-associated coronavirus 2 (SARS-CoV-2) infection are typically mild in children.[1–7] However, severe symptoms and even deaths from Coronavirus Disease 2019 (COVID-19) can occur.[8,9] A separate pediatric-specific clinical presentation arises in the form of an entity termed Multisystem Inflammatory Syndrome (MIS-C), characterized by a persistent acute febrile illness progressing to multiorgan dysfunction.[10,11]

The prevalence of acute liver injury (ALI) in adult patients with COVID-19 ranges from 15%-78%, with most studies reporting 20%-30% among hospitalized patients.[12–14] ALI, defined as an elevation in aminotransferases and typically presenting as hepatocellular histological injury with mild acute cholestasis, has been documented in adults and children with SARS-CoV-2 infection. Most adult patients experience transient mild to moderate elevation of liver enzymes.[12–16] Severe ALI (alanine aminotransferase [ALT] values 5x above the upper limit of normal [ULN]) was reported to correlate with disease severity and poor outcomes in adults, including death.[13,17]

In contrast, less is known about the association between elevated ALT (E-ALT) and disease severity in children with SARS-CoV-2. In this study, we looked at elevations in ALT (E-ALT), as a surrogate marker for liver injury, similar to what has been done in adult studies.[13] We previously published a focused description of the association of hepatitis with disease severity in a cohort of 44 patients with MIS-C included within this report.[18] We now further expand the scope of understanding of liver involvement in two clinical presentations of SARS-CoV-2. We provide critical data on its associating factors, epidemiology, and their contribution to the consequences of elevated ALT in children with COVID-19 versus MIS-C.

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