IV Post

San Diego, California - Family members of children diagnosed with non-alcoholic fatty liver disease (NAFLD) should be considered at high risk for the disease and tested for it as part of a routine medical examination, even if they don’t show symptoms, according to a recent study by researchers at the University of California, San Diego School of Medicine. 

“As we suspected, NAFLD  is not simply about weight, but rather is highly familial and likely genetic,” said principal investigator Jeffrey B. Schwimmer, MD, associate professor of pediatrics and director of the Fatty Liver Clinic at Rady Children’s Hospital-San Diego. 

NAFLD is now the most common cause of chronic liver disease is the United States. NAFLD refers to a spectrum of liver disease that begins with liver cells abnormally storing fat, in the absence of chronic alcohol use. NAFLD can be mild in some people, but in a subset with the progressive form (steatoehepatitis or NASH) there is risk for cirrhosis, liver cancer, and liver-related death.  Based upon clinical observation, doctors have speculated that NAFLD may be a genetic disease, but lacked scientific support for this idea. 

The current study takes a major step in building the case that NAFLD is a genetic disease. The research team studied 44 children with and without NAFLD and 152 family members of these children.  In order to determine the amount of fat in the liver of each participant they used a state of the art magnetic resonance imaging (MRI) technique developed at UC San Diego.  The researchers also performed tests to exclude other factors that can cause a fatty liver other than NAFLD.

The researchers found that whether or not a given person had NAFLD was highly heritable—whether or not the child had NAFLD was a major determinant of the amount of liver fat present in the other family members.  In the families of overweight children without NAFLD, siblings and parents had NAFLD at rates that were similar to the background population’s rates of NAFLD.  The rates of NAFLD were much higher in family members of children with NAFLD; it was present in 59% of siblings and 78% of parents.  In most cases the person did not know that they had the disease. In a few cases the disease was already very advanced even in the absence of symptoms.

“Being overweight is a risk factor for NAFLD, but this is strongly modified by the underlying genetics,” said Schwimmer.  “So some people can have high body weights without any storage of fat in the liver.  But in susceptible families, there’s an additive effect.  Regardless of weight, they are more likely to have NAFLD for genetic reasons.  In addition, the more overweight such a person is, the more likely they are to have dangerous amounts of fat in their liver.”

The researchers recommend that if one family member tests positive for NAFLD, other family members should talk to their doctors immediately.  Early detection could catch NAFLD at a stage where the disease is reversible and further complications may be prevented before cirrhosis sets in.

Schwimmer hopes that further studies will disclose specific genetic and environmental factors that influence the development and severity of the disease, which could provide helpful information to a wide array of health care practitioners.

“Understanding that this disease runs in families may help an entire family create a healthy lifestyle with regular exercise and a heart-healthy—liver healthy diet,” said Schwimmer. 

After participating in the study, Susanne Hernandez and her family have already changed the way they live.  Like so many children with NAFLD, her 12 year-old son was identified on accident.  Because of his asthma, he was scheduled to participate in a clinical trial for asthma management, but first had screening blood tests including an ALT.  This test led to evaluation by a gastroenterologist and the surprising finding of severe liver disease.  A quick web search led to the family becoming part of Schwimmer’s research.  Debbie, her son and her husband are now being treated for liver disease.  Luckily, their daughter is not affected.

“This study made us more aware that we have to make changes,” explained Hernandez.  “After getting proper attention, my son is much more alert, and we pay attention to his fatigue, keeping him hydrated and we’re on a good nutrition routine.” 

Previous studies by UC San Diego investigators showed that:

• NAFLD is present in 9.6 percent of the children and adolescents living in San Diego County
• Nearly all children with NAFLD are insulin resistant

In children, NAFLD is a major risk factor for diabetes and cardiovascular disease.

Additional contributors include Manuel Celedon, Joel Lavine, MD, PhD, UCSD department of pediatrics; Takeshi Yokoo, MD, Masoud Shiehmorteza, Michael S. Middleton, MD, PhD, and Claude B. Sirlin, M.D., and Alyssa Chavez, UCSD department of radiology; Rany Salem, PhD, Nzali Campbell, PhD and Nicholas Schork, PhD, Scripps Health and The Scripps Research Institute.

This work was funded by grants from the National Institutes of Health, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center of Minority Health and Health Disparities and the National Center for Research Resources.