COVID-19 and pediatric fatty liver disease: Is there interplay?

Abstract

The rapid global spread of coronavirus disease 2019 (COVID-19) infection has become a major health issue with higher morbidity and mortality rates. Besides respiratory symptoms, a growing body of evidence indicates a variety of gastrointestinal manifestations including liver involvement. In this regard, several data supported an association between COVID-19 infection and liver injury in adults, while in children there is compelling but currently limited evidence. In particular, patients with COVID-19 have shown a higher risk of liver injury (mainly expressed as increased transaminase levels or hepatic steatosis). Conversely, a greater risk of more severe forms of COVID-19 infection has been observed in subjects with pre-existing chronic liver diseases. The dramatic interplay between COVID-19 and liver damage has been related to the inflammatory pathways chronically active in patients with nonalcoholic fatty liver disease and acutely in those affected by COVID-19, but other different pathogenic mechanisms have also been supposed. Of note, patients with previous metabolic comorbidities also had a higher risk of severe COVID-19 infection. This emphasizes the pathogenic interrelation of the inflammatory pathways with a dysregulated metabolic milieu in COVID-19 patients. Taking into account the prognostic role of fatty liver in COVID-19 patients and its intrinsic relationship with metabolic abnormalities even in childhood, a strict monitoring of this condition is recommended. We aimed to summarize the most recent evidence regarding the potential interplay between pediatric fatty liver and COVID-19.

Serum homocysteine level in pediatric patients with COVID‐19 and its correlation with the disease severity

“…28 Previous studies found increased liver enzymes in 25% of children with COVID-19, which reached 50% in severe and critically ill individuals. 29 Omran et al 30 reported that elevated liver enzymes are predictors of the severity of COVID-19. In the current study, ALT and AST had a positive correlation with Hcy levels, which is consistent with the findings of Lv et al 31 Although Hcy levels rise in patients with renal failure, we could not detect a link between Hcy and serum creatinine.…”

“…COVID‐19 liver injury could be caused by direct viral invasion via angiotensin‐converting enzyme 2 receptors in the liver, or it could be immune‐mediated or drug‐induced 28 . Previous studies found increased liver enzymes in 25% of children with COVID‐19, which reached 50% in severe and critically ill individuals 29 . Omran et al 30 reported that elevated liver enzymes are predictors of the severity of COVID‐19.…”

Emerging mechanistic insights of selective autophagy in hepatic diseases

“…Although most infected individuals are asymptomatic, the typical COVID-19 disease presents as mild to severe progressive pneumonia. SARS-CoV-2 infection can affect all the systems of the human body, and emerging data suggest that COVID-19 has pulmonary and extrapulmonary manifestations including hepatic injury subsequently progressing to multiorgan damage and death particularly in elderly patients ( Di Sessa et al, 2021 ).…”

“…Metabolic-associated fatty liver disease (MAFLD) patients have a higher risk of SARS-CoV-2 infection and increased liver dysfunction in comparison to patients without MAFLD. Dysregulated hepatic immunity in NAFLD patients can participate in COVID-19 pathogenesis because immune cells (e.g., Kupffer cells) can produce active cytokines and aggravate or contribute to the cytokine storm ( Di Sessa et al, 2021 ).…”

“…Although the emerging role of lipophagy in NAFLD is still not firmly established, activation of lipophagy is apparent during NAFLD progression (Czaja et al, 2013). APOB (apolipoprotein B)-oriented LDs (Ohsaki et al, 2006) and bortezomib-induced Mallory Denk bodies (MDBs) in liver cells (Strnad et al, 2008;Harada et al, 2008;Harada, 2010) Sessa et al, 2021). Similar to NAFLD, AFLD caused by chronic alcohol abuse has a wide spectrum of pathogenesis such as steatosis, alcoholic hepatitis and fibrosis which can develop into cirrhosis and even HCC (Czaja et al, 2013;Eid et al, 2013a;Eid et al, 2013b;Niture et al, 2021).…”