Does Non-Alcoholic Fatty Liver Disease Run in Families?

Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease around the world, which affects up to 100 million individuals globally. A new study has found that this condition may, at least in part, be heritable, prompting researchers to search for clinically-relevant biomarkers of the disease.

Specifically, the research found that serum metabolites that can be detected in the blood – and are often an indicator of altered metabolic pathways in disease states – are heritable among families. The results of the study were presented at the American Association for the Study of Liver Diseases’ annual Liver Meeting.

NAFLD also shares a genetic risk factors with high blood pressure, high blood glucose and high cholesterol – a group of conditions collectively known as metabolic syndrome. These conditions can progress into more serious diseases, including diabetes and heart disease.

To assess the heritability of serum metabolites associated with NAFLD, researchers from the NAFLD Research Center at the University of California, San Diego, studied a small sample of 156 individuals in Southern California. Since the study was looking at heritability, the investigators included “37 identical twins, 13 fraternal twins, and 28 sets of sibling/sibling and parent/offspring pairs.

“If a serum metabolite is heritable and has a shared gene effect with NAFLD, then it could be a useful biomarker of the disease and could potentially be targeted to improve NAFLD in the future,” said Dr. Cyrielle Caussy, an endocrinologist from Lyon 1 University and a visiting scholar at the NAFLD Research Center.

The researchers used MRI to qualify the health of the liver in each participant based on levels of fat and fibrosis. They also collected blood samples in order to quantify their serum metabolites, and included both environmental and genetic factors in their prediction of heritability.

The researchers identified 36 individuals from the cohort which showed signs of NAFLD. They also found that 440 of a total 713 serum metabolites were heritable, with 56 having a shared gene effect with NAFLD, after confounding factors were controlled for.

“We found that the novel serum metabolite, phenyllactate (derived from gut‐biome), had a significant shared gene effect with NAFLD,” said Caussy. “This suggests a potential link between genetics and gut‐microbiome in the development of NAFLD and provides evidence that several serum metabolites associated with NAFLD are heritable.”

Not only could these biomarkers help physicians assess the severity of NAFLD, but they may also help drug developers assess the effectiveness of new treatments for the disease. The researchers plan to conduct further studies to validate the serum metabolites as biomarkers for NAFLD.