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Ariel E. Feldstein, M.D 1,2
Marsha H. Kay, M.D, FACG 1
From the Department of Pediatric Gastroenterology
and Nutrition1
and Department of Cell Biology2, Cleveland Clinic Foundation,
Cleveland, OH
What is Nonalcoholic Fatty Liver Disease (NAFLD)
/ Nonalcoholic Steatohepatitis (NASH)?
NAFLD refers to a group of conditions where there is accumulation
of excess fat in the liver of people who drink little or no alcohol.
The most common form of NAFLD is a non serious condition called
fatty liver. In fatty liver, fat accumulates in the liver cells.
Although having fat in the liver is not normal, by itself it probably
does not damage the liver. A small group of people with NAFLD may
have a more serious condition named non-alcoholic steatohepatitis
(NASH). In NASH, fat accumulation is associated with liver cell
inflammation and different degrees of scarring. NASH is a potentially
serious condition that may lead to severe liver scarring and cirrhosis.
Cirrhosis occurs when the liver sustains substantial damage, and
the liver cells are gradually replaced by scar tissue (see figure),
which results in the inability of the liver to work properly. Some
patients who develop cirrhosis may eventually require a liver transplant
(surgery to remove the damaged liver and replace it with a “new” liver).
How common is NAFLD / NASH?
NAFLD is a very common disorder. It is estimated that NAFLD affects
up to 20 percent of adults and nearly 5 percent of children. Obesity
is thought to be the most common cause of fatty infiltration of
the liver. Some experts estimate that about two thirds of obese
adults and half of obese children may have fatty liver. About 2
to 5 percent of adult Americans and up to 20 percent of those who
are obese may suffer from the more severe condition NASH. The number
of children who have NASH is not known. In the past ten years the
rate of obesity in our country has doubled in adults and tripled
in children and teenagers, which may explain why NAFLD and NASH
are becoming more common.
What causes NAFLD / NASH?
NAFLD is part of the metabolic syndrome characterized by diabetes,
or pre-diabetes (insulin resistance), being overweight or obese,
elevated blood lipids such as cholesterol and triglycerides, as
well as high blood pressure. Not all patients have all the manifestations
of the metabolic syndrome. Less is known about what causes NASH
to develop. Researchers are focusing on several factors that may
contribute to the development of NASH. These include:
- Oxidative stress (imbalance between pro-oxidant and anti-oxidant
chemicals that lead to liver cell damage)
- Production and release of toxic inflammatory proteins (cytokines)
by the patient’s own inflammatory cells, liver cells, or
fat cells
- Liver cell necrosis or death, called apoptosis
What are signs and symptoms of NAFLD / NASH?
The majority of individuals with NAFLD have no symptoms and a
normal examination. Children may exhibit symptoms such as abdominal
pain, which may be in the center or the right upper part of the
abdomen, and sometimes fatigue. However, other causes of abdominal
pain and fatigue should be
considered. On physical examination the liver might be slightly
enlarged and some children may have patchy, dark discoloration
of the skin present (acanthosis nigricans) most commonly over the
neck and the under arm area.
How is NAFLD / NASH diagnosed?
The diagnosis of NAFLD is usually first suspected in an overweight
or obese person who is found to have mild elevations in their liver
tests during a routine blood testing. Some experts are now recommending
that every obese child or adolescent should have these liver enzymes
checked. However NAFLD can be present with normal liver blood tests.
The diagnosis of NAFLD is confirmed by imaging studies, most commonly
a liver ultrasound, showing accumulation of fat in the liver. Fat
accumulation in the liver can also be caused by excess alcohol
intake, certain medications, viral hepatitis, autoimmune liver
disease, and metabolic or inherited liver disease. These need to
be excluded as causes of fatty liver disease in order to confirm
the diagnosis of NAFLD. Currently, the only reliable way of telling
whether a person has NASH or simple fatty liver is by a liver biopsy.
In this procedure, a small needle is inserted through the skin
after local anesthesia is given to obtain a small piece of the
liver for microscopic evaluation. NASH is diagnosed when examination
of this piece of liver under the microscope shows fatty infiltration
of the liver in addition to inflammation and different degrees
of scarring. If only fat is present, then the diagnosis of simple
fatty liver is made. The liver biopsy provides essential information
regarding the degree of scarring within the liver, which would
not be apparent on a blood test, ultrasound, or an x-ray alone.
Liver biopsy rarely can be associated with serious risks including
bleeding and patients should discuss the risks and benefits of
the procedure with their physician.
What are the risks of having NAFLD / NASH?
Most people with NAFLD, especially those with simple fatty liver
with no inflammation, have little or no problems from the condition.
In contrast, about a quarter of people with NASH may have scarring
of the liver that gets worse with time. In general, the progression
of scarring is slow and can take years and even decades to occur.
In some patients the scarring can stabilize and in persons who
have lost significant amounts of weight there are cases where scarring
has been shown to reverse. In others, the progression continues
with scar tissue accumulating in the liver, leading to cirrhosis.
NASH is an increasingly common reason for liver transplantation
in the United States.
How is NAFLD / NASH treated?
There is currently no medical treatment that reverses fatty liver
disease and causes fat within the liver to resolve. As mentioned,
a few studies have suggested that weight loss may be associated
with regression of fat within the liver. Therefore, the most important
recommendations for people with fatty liver are to lose weight
if they are overweight or obese, increase their physical activity,
follow a balanced diet and avoid alcohol and unnecessary medications.
In patients with NASH, the more severe form of NAFLD, these same
recommendations may be helpful. It is also important to control
diabetes and treat elevated cholesterol levels when appropriate.
Development of medications that could treat NAFD and NASH is an
area of intense research. Factors currently being evaluated by
physicians and scientists to decrease the amount of fat in the
liver include:
- Weight reduction (diet + exercise, medications, surgery)
- Lipid lowering medications
- Insulin sensitizers (medications)
- Decrease the amount of liver inflammation by administering
anti-oxidant medications, anti-apoptotic medications and anti-cytokine
medications
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