Clinical implications of understanding the association between oxidative stress and pediatric NAFLD

ABSTRACT

Introduction: Oxidative stress is central to the pathogenesis of non-alcoholic steatohepatitis. The reactive oxygen species (ROS) that characterise oxidative stress are generated in several cellular sites and their production is influence by multi-organ interactions.

Areas covered: Mitochondrial dysfunction is the main source of ROS in fatty liver and is closely related to endoplasmic reticulum stress. Both are caused by lipotoxicity and together these three factors form a cycle of progressive organelle damage, resulting in sterile inflammation and apoptosis. Adipose tissue inflammation and intestinal dysbiosis provide substrates for ROS formation and trigger immune activation. Obstructive sleep apnea and abnormal divalent metal metabolism may also play a role.

Expert commentary: The majority of available high-quality data originates from studies in adults and there are fewer therapeutic trials performed in pediatric cohorts, therefore conclusions are generalised to children. Establishing the role of organelle interactions, and its relationship with oxidative stress in steatohepatitis, is a rapidly evolving area of research.

KEYWORDS:

• NAFLD
• pediatric
• oxidative stress
• mitochondrial dysfunction
• lipotoxicity
• steatohepatitis

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.