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

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.

Metabolic-associated fatty liver disease from childhood to adulthood:State of art and future directions

In 2020,an international group of experts proposed to replace the term of nonalcoholic fatty liver disease with metabolic-associated fatty liver disease(MAFLD).This recent proposal reflects the close association of fatty liver with metabolic derangements,as demonstrated by previous robust data.Several factors[including genetics,inflammation,metabolic abnormalities,insulin resistance(IR),obesity,prenatal determinants,and gut–liver axis]have been found to be involved in MAFLD pathophysiology,but this tangled puzzle remains to be clearly understood.In particular,IR has been recognized as a key player in metabolic impairments development in children with fatty liver.On this ground,MAFLD definition focuses on the pathophysiological basis of the disease,by emphasizing the crucial role of metabolic impairments in this condition.Although primarily developed for adults,MAFLD diagnostic criteria have been recently updated with an age-appropriate definition for sex and age percentiles,because of the increasing attention to cardiometabolic risk in childhood.To date,accumulating evidence is available on the feasibility of MAFLD definition in clinical practice,but some data are still conflicting in highly selected populations.Considering the growing prevalence worldwide of fatty liver and its close relationship with metabolic dysfunction both in children and adults with subsequent increased cardiovascular risk,early strategies for MAFLD identification,treatment and prevention are needed.Novel therapeutic insights for MAFLD based on promising innovative biological techniques are also emerging.We aimed to summarize the most recent evidence in this intriguing research area both in children and adults.