The Progression and Natural History of Pediatric Nonalcoholic Fatty Liver Disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States. Childhood NAFLD is associated with hepatic and non-hepatic morbidity and mortality. Non-hepatic associations included cardiovascular, metabolic, pulmonary and psychological disorders. Cardiovascular conditions observed in childhood include left ventricular dysfunction. Furthermore, childhood obesity is associated with greater odds of having hepatocellular carcinoma as an adult. Evidence suggests that NAFLD may begin in utero in children of diabetic mothers. However, NAFLD typically is diagnosed between the ages of 10–13 years. The actual onset of disease for most children is not known. At diagnosis 10–25% of children can have advanced fibrosis. In the most severe cases, children can progress within a few years to cirrhosis and end-stage liver disease. Quality longitudinal data of the natural history of pediatric NAFLD are limited. Available data suggest that children with NAFLD are at risk for higher mortality rates as young adults. However, NAFLD is a heterogeneous disease and natural history is expected to vary considerably from child to child. Thus rigorous efforts for structured diagnosis and follow-up are a priority to better develop the understanding of outcomes in pediatric NAFLD needed to provide accurate counseling to children and their families.

Developmental origins of NAFLD: a womb with a clue

“…Whether exposure of liver macrophages prenatally to maternalderived factors or perinatally to infant gutderived factors interferes with physiological programming of the tissue such that it aberrantly assumes an adult phenotype and promotes scarring and fibrosis is unclear. Given the severity and rapid progression of paediatric liver disease upon diagnosis 5 , future studies are required to identify the early microenvironmental features that programme liver macrophages, activate specific phenotypes conducive to chronic inflammation, or prevent resolution and promote continuous activation of proremodelling and/or profibrotic pathways that contribute to progression of fatty liver disease.…”

“…The most common chronic liver disease worldwide, NAFLD increases the risk of cardiovascular events eightfold and type 2 diabetes mellitus (T2DM) threefold 3 , and is a strong risk factor for hepatocellular carcinoma (HCC) 4 . At the time of paediatric NAFLD diagnosis, 25–50% of children have NASH and 10–25% have advanced fibrosis 5 . For many decades, it was thought that NAFLD was predominantly driven by obesity in the setting of genetic susceptibility.…”

Magnetic resonance elastography measured shear stiffness as a biomarker of fibrosis in pediatric nonalcoholic fatty liver disease

“…In adults, the presence and severity of fibrosis are important predictors of the long‐term risk for cirrhosis, hepatocellular carcinoma, and liver‐related mortality . Natural history studies to determine the significance of presence and severity of fibrosis on long‐term outcomes in children are lacking . Fibrosis and advanced fibrosis have been reported in 40%‐90% and 6%‐34%, respectively, of children with NAFLD .…”

Effect of Restriction of Foods with High Fructose Corn Syrup Content on Metabolic Indices and Fatty Liver in Obese Children

“…NAFLD is the most common cause of chronic liver disease, which includes a spectrum ranging from simple steatosis to progressive nonalcoholic steatohepatitis with or without cirrhosis [10]. NAFLD is frequently associated with obesity, may appear early in life, and increases with age [11].…”