Metabolically healthy lean people may develop
non-alcoholic fatty liver disease (NAFLD), although this is much more common
among people with obesity and metabolic abnormalities, according to research presented at the AASLD Liver Meeting last month in San
NAFLD and its more severe form, non-alcoholic steatohepatitis (NASH),
are a growing concern as rates of obesity increase worldwide. NAFLD and NASH
are usually associated with the metabolic syndrome, a cluster of conditions – including
excess abdominal fat, high blood pressure, insulin resistance, and elevated
LDL cholesterol and triglycerides – that
raise the risk for cardiovascular disease.
The build-up of fat in the liver triggers inflammation and development
of scar tissue (fibrosis), which over time can lead to cirrhosis and liver
cancer. Now that hepatitis B
vaccination is widespread and most people with hepatitis C can be cured with direct-acting
antivirals, fatty liver disease accounts for a growing share of advanced liver
disease and liver transplants. But to date there are no good treatments
and management relies on lifestyle changes such as weight loss.
Abnormal fat deposits in the liver.
Pegah Golabi of Inova Health System in Virginia
and colleagues conducted a study to
determine the prevalence and long-term outcomes of NAFLD among lean and
metabolically normal individuals.
United States, around 7 to 10% of people with NAFLD are considered lean, the
researchers noted as background. Although these individuals appear to be less
metabolically unhealthy than obese people with NAFLD, they have more metabolic
abnormalities than lean people without NAFLD. However, NAFLD among people who
are both lean and metabolically normal is not well understood.
team analysed data from the National
Health and Nutrition Examination Survey (NHANES), an ongoing household survey
that asks participants about their health status and collects specimens for
testing. This study used data from NHANES III, covering 1988 to 1994. These
were linked to mortality data in the National Death Index. The researchers had
access to data about overall mortality and cardiovascular deaths, but not
liver-related mortality because it was not among the top ten causes of death.
The study population included
3242 lean and 2952 obese individuals. Lean people were defined as those with a
body mass index (BMI) of 25 or lower and a waist circumference of 90cm or less
for men or 80cm or less for women. Obese people were those with a BMI over 30
and waist circumference over 102cm for men or over 88cm for women.
NAFLD was defined as moderate to
severe steatosis, or fat accumulation in the liver, as determined by liver
ultrasound, in the absence of other causes of chronic liver disease such as
hepatitis B or C or heavy alcohol use. People without diabetes, hypertension or
elevated blood lipids were considered metabolically normal. Metabolically
normal people were younger on average and more likely to be women (69% vs 42%).
Among the population overall,
19.6% had NAFLD, including 18.1% with any metabolic conditions and 1.5%
considered metabolically normal. As expected, obese people had the highest
prevalence of NAFLD, at 39.4%, including 38.4% with any metabolic conditions
and 1.0% who were metabolically normal. In the lean group, 7.7% had NAFLD,
including 5.5% with metabolic conditions and 2.2% considered metabolically
Overall, lean men and women were
about equally likely to have NAFLD. The prevalence of lean NAFLD with no
metabolic abnormalities was 4.4% among men and 7.1% among women.
NAFLD rates rose among lean
individuals with more metabolic abnormalities, reaching 15.3% for men and 23.7%
for women with diabetes, hypertension and abnormal blood lipids. The rate
reached 15.0% for men with diabetes alone.
In the obese group, having
multiple abnormalities was again associated with the highest likelihood of
NAFLD for both men (65.6% and 49.3%, respectively). But women with diabetes
alone (57.9%) and men with abnormal lipids alone (43.9%) also had high rates.
In the lean group, there was no
consistent NAFLD pattern according to race or ethnicity. In the obese group, in
contrast, Mexican-Americans were most likely to have NAFLD, and non-Hispanic
white people had a higher rate than black people.
After controlling for other
factors, diabetes was an independent risk factor for NAFLD in both lean and
obese people, more than doubling the risk in the lean group.
The most common causes of death
among lean people with NAFLD were cancer (31.6%) and cardiovascular disease
(20.9%). However, during a median follow-up period of about 19 years, there
were no cardiovascular deaths – and only eight deaths from any cause – among those
with NAFLD but no metabolic abnormalities
"Presence of [diabetes
mellitus] is the most important driver of NAFLD," the researchers
concluded. "Lean NAFLD individuals without any component of metabolic
syndrome do not seem to have increased overall or cardiovascular