According to research published in, liver disease in children could be caused by prenatal exposure to various environmental chemicals. JAMA Network Open. Researchers reported that a second pediatric study showed that children with non-alcoholic fat liver disease (NAFLD), are more likely to develop type 2 diabetes. Clinical Hepatology and Gastroenterology.
NAFLD, which is caused by the accumulation of fat within the liver, and NASH (non-alcoholic steatohepatitis) are both responsible for a rising number of liver-related deaths and advanced liver disease. It is common for liver fat to be associated with obesity and diabetes. Therefore, it is also known as metabolic-associatedfatty liver disease, or MAFLD. Fatty liver disease can eventually lead to liver cancer, cirrhosis, and fibrosis. There are no approved medical treatments that can be used to manage fatty liver disease. Instead, lifestyle changes like weight loss and exercise are important.
NAFLD is the most common liver disease in children. There are approximately 5 to 8 millions cases in the United States. NAFLD is found in approximately 6%-10% of the general population of children and one-third of those with obesity. Children are also increasingly suffering from type 2 diabetes.
Chemical Exposure
Damaskini Vavi, MD, MSPH, PhD of the Icahn School of Medicine in Mount Sinai in New York City and her colleagues examined the relationship between prenatal exposure and liver injury in children to endocrine-disrupting chemical.
Endocrine-disrupting chemical, which can affect hormonal systems, is a large category of environmental pollutants. These include pesticides. Plastics. Toxic metals. Flame retardants. They are commonly found in furniture, nonstick cookware and other common products. Research has previously shown that these chemicals can cause liver injury and fatty liver diseases, but it is not known what the effects of prenatal exposure will be.
The population-based cohort study was based on data from 1,108 mothers-children pairs from six European countries. It was conducted between April 2003 to February 2016. The mothers were on average 31 years old at delivery. Their children were, on average 8 years, at the follow-up. The proportion of girls and boys was about equal.
Researchers found levels of 45 chemicals in blood, urine, and umbilical cord blood of the mothers. Pesticides, metals and phthalates were all included in the list. The team detected liver disease markers in the blood of the children aged between 6 and 11.
Liver injury was defined as blood levels of the liver enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT) or gamma-glutamyltransferase (GGT) above the 90th percentile. Endocrine-disrupting chemical exposures resulted in higher levels of these enzymes in children. Additionally, there was a significant correlation between higher levels cytokeratin-18, which is a biomarker of liver cell death, and increased exposure to polychlorinated diphenyls (PBDEs), and the presence of polychlorinated triphenyls (PCBDEs).
The risk of liver injury in children who were exposed to organochlorine insecticides, perfluoroalkyl compounds, PBDEs or metals during pregnancy ranged from 44% to 121%. Prenatal exposures to metals, perfluoroalkyl compounds, PBDEs and/or organochlorine pesticides were all linked to liver injury. Boys were more at risk for liver injury from exposure to metals than girls. However, liver injury rates were lower when prenatal exposure was to high-molecularweight phthalates or phenols.
The study concluded that 253 children in the higher-risk category were at greater risk of liver injury. Children at greater risk for liver injury were more likely not to be from racial or cultural minorities, and to be obese or overweight than those at lower risk. Their mothers were more likely not to have received a good education and to have a higher body-mass index. Studies have shown that maternal obesity is a risk factor in NAFLD among children.
“These findings show that early life exposure to many endocrine-disrupting chemicals is a risk factor for pediatric non-alcoholic fatty liver disease and draw attention for additional investigation needed to elucidate how environmental chemical exposures may interact with genetic and lifestyle factors in the pathogenesis of liver disease,” Valvi said in a Press release.
NAFLD and diabetes
Diabetes and fatty liver disease are linked in adults. However, children have not been extensively studied. Jeffrey Schwimmer, MD of the University of California San Diego and his colleagues evaluated the incidence of type 2 Diabetes and the associated risk factors in children living with NAFLD.
“There is a growing public health crisis as children with diabetes mature into adults with diabetes,” Schwimmer said in a Press release. “We need to better understand how NAFLD contributes to type 2 diabetes risk in children so that we can actively work to prevent it.”
Participants were part of the Nonalcoholic Steatohepatitis clinical research network. Lab tests and clinical histories were used for the assessment of type 2 diabetic occurrence in children with NAFLD.
The study population consisted of 892 children with NAFLD. About three quarters of the children were male and the average age was thirteen years. They were closely followed for almost four years.
Type 2 diabetes was found in 63 children (6.6%) at the beginning of the study. At the end of the follow up period, 97 additional children (11.0%) had been diagnosed with diabetes. 16.8% of children developed type 2 diabetes during the course the study.
Type 2 diabetes was diagnosed in 3,000 people per 100,000 years. The study found that 1 in 6 children had developed type 2 diabetes by the end. Type 2 diabetes incidence was higher in girls than it was for boys. Additional risk factors include severe obesity and liver injury. This includes the presence of fat or scar tissue (fibrosis).
“These findings have clinical implications for gastroenterologists caring for children with NAFLD,” Schwimmer said. “They should be aware of the risk and provide monitoring, anticipatory guidance and lifestyle interventions that help their patients avoid developing type 2 diabetes.”
Click here for the complete study JAMA Network Open.
Click here for the complete study Clinical Hepatology and Gastroenterology.
Click here to read more about fatty liver disease.
