COVID-19 and Liver Damage: Narrative Review and Proposed Clinical Protocol for Critically ill Pediatric Patients

Luglio, Michele; Tannuri, Uenis; Carvalho, Werther Brunow de; Bastos, Karina Lucio de Medeiros; Rodriguez, Isadora Souza; Johnston, Cíntia; Delgado, Artur Figueiredo

doi:10.6061/clinics/2020/e2250

Cited by 14 publications

(22 citation statements)

References 44 publications

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“…13,17,18,21 The E-ALT mechanism in SARS-CoV-2 is not fully understood, but under investigation are an effect of viral lesions in hepatic/cholangiocyte cells, inflammatory damage, hypoxic/shock-related circulatory compromise, endothelial dysfunction, microthrombi formation, and drug toxicity. [22][23][24] The direct viral cytopathic effect in the pathophysiology of E-ALT via the cell receptors for angiotensin-converting enzyme II and transmembrane protease serine 2, invoked in the transmission of SARS-CoV-2, is supported by the demonstration of SARS-CoV-2 in the liver parenchyma in patients with higher liver enzyme elevation. 25 As previously reported, children with E-ALT in the COVID-19 cohort more frequently carried an underlying medical condition such as immunocompromised state (including malignancy), or CLD, significantly contrasting with those with E-ALT in MIS-C. 3,4,26 In our study, although children with MIS-C had >2× higher odds of any degree of elevation in ALT levels compared to children with COVID-19 (51% vs 31%), severe elevation, defined as ALT >200 U/L was observed at a higher frequency in children with COVID-19 (8% vs 4%) (Figure 1).…”

Section: Discussionmentioning

confidence: 99%

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

Perez

Cantor

Rudolph

et al. 2021

Liver International

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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.

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Section: Discussionmentioning

confidence: 99%

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

Perez

Cantor

Rudolph

et al. 2021

Liver International

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“…Therefore, the pathophysiology of the liver involvement in COVID-19 and MIS-C is still unclear, but it is believed that the injury might be caused by hepatocellular infection with direct cytopathic effects of SARS-CoV-2 or an immune-mediated response with inflammatory damage. In addition, hypoxic/shock-related circulatory compromise, endothelial dysfunction, microthrombi formation and drug-induced liver injury (e.g., corticosteroids, lopinavir, ritonavir, tocilizumab and remdesivir) may be involved [ 12 ]. COVID-19-associated liver injury is defined as any liver damage occurring during disease course and treatment of COVID-19 patients, with or without pre-existing liver disease [ 13 ] and typically leads to a temporary moderate elevation of liver tests without significant hepatic synthetic function impairment.…”

Section: Discussionmentioning

confidence: 99%

New Onset of Hepatic Steatosis Post-Severe Multisystem Inflammatory Syndrome in Children (MIS-C): A Case Report

Sica¹,

Pennoni²,

Penta³

et al. 2021

IJERPH

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The emergence of Multisystem Inflammatory Syndrome (MIS-C) following SARS-CoV-2 infection in children and adolescents provided a new diagnostic and management challenge as there is limited knowledge about this condition and its natural history. In existing literature on MIS-C, there are currently no data about long-term outcomes. We report the case of a 14-year-old boy, with no significant past medical history, who presented a condition of multiorgan dysfunction due to MIS-C, after a SARS CoV-2 infection, and subsequent clinical-laboratory signs of hepatic steatosis at short-term follow-up. The case suggests how hepatic steatosis may be a possible sequela following SARS-CoV-2 infection, MIS-C and its medical treatment. Therefore, a close and long-term follow-up is needed to establish the pathophysiology and the evolution of this condition in patients following MIS-C.

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“…Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection is a systemic disease, responsible of a variety of clinical manifestations, affecting not only upper and lower respiratory tract but also gastrointestinal system and liver 1 . Small case series have reported hepatic involvement in up to 60% of infected patients, especially in severe and critical cases of coronavirus disease 2019 (COVID‐19) 1,2 . In children aged 0–3 years, transient mild elevation in serum aminotransferases is common during symptomatic phase, with an overall prevalence of approximately 29% 3 .…”

Section: Introductionmentioning

confidence: 99%

Severe hypertransaminasemia during mild SARS‐CoV‐2 infection: A pediatric case report and literature review

Palpacelli¹,

Martelli²,

Lattanzi³

et al. 2021

Pediatric Investigation

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Introduction Liver injury during SARS‐CoV‐2 infection has a multifactorial pathogenesis and it is frequent in pediatric cases. Case presentation We report a case with severe hypertransaminasemia associated with mild SARS‐CoV‐2 infection. Conclusion This highlights the potential need of hepatic function evaluation during acute illness and follow‐up even in non‐critically ill children with COVID‐19.

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COVID-19 and Liver Damage: Narrative Review and Proposed Clinical Protocol for Critically ill Pediatric Patients

Cited by 14 publications

References 44 publications

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

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

New Onset of Hepatic Steatosis Post-Severe Multisystem Inflammatory Syndrome in Children (MIS-C): A Case Report

Severe hypertransaminasemia during mild SARS‐CoV‐2 infection: A pediatric case report and literature review

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