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Non-Alcoholic Fatty Liver Disease is in the
Family
Newswise — 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
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