Nonalcoholic steatohepatitis or NASH is a common, often "silent"
liver disease. It resembles alcoholic liver disease, but occurs in
people who drink little or no alcohol. The major feature in NASH is fat
in the liver, along with inflammation and damage. Most people with NASH
feel well and are not aware that they have a liver problem.
Nevertheless, NASH can be severe and can lead to cirrhosis, in which
the liver is permanently damaged and scarred and no longer able to work
properly.
NASH affects 2 to 5 percent of Americans. An additional 10 to 20
percent of Americans have fat in their liver, but no inflammation or
liver damage, a condition called "fatty liver." Although having fat in
the liver is not normal, by itself it probably causes little harm or
permanent damage. If fat is suspected based on blood test results or
scans of the liver, this problem is called nonalcoholic fatty liver
disease (NAFLD). If a liver biopsy is performed in this case, it will
show that some people have NASH while others have simple fatty liver.
Both NASH and NAFLD are becoming more common, possibly because of
the greater number of Americans with obesity. In the past 10 years, the
rate of obesity has doubled in adults and tripled in children. Obesity
also contributes to diabetes and high blood cholesterol, which can
further complicate the health of someone with NASH. Diabetes and high
blood cholesterol are also becoming more common among Americans.
Biliary system.
Diagnosis
NASH is usually first suspected in a person who is found to have
elevations in liver tests that are included in routine blood test
panels, such as alanine aminotransferase (ALT) or aspartate
aminotransferase (AST). When further evaluation shows no apparent
reason for liver disease (such as medications, viral hepatitis, or
excessive use of alcohol) and when x rays or imaging studies of the
liver show fat, NASH is suspected. The only means of proving a
diagnosis of NASH and separating it from simple fatty liver is a liver
biopsy. For a liver biopsy, a needle is inserted through the skin to
remove a small piece of the liver. NASH is diagnosed when examination
of the tissue with a microscope shows fat along with inflammation and
damage to liver cells. If the tissue shows fat without inflammation and
damage, simple fatty liver or NAFLD is diagnosed. An important piece of
information learned from the biopsy is whether scar tissue has
developed in the liver. Currently, no blood tests or scans can reliably
provide this information.
Liver biopsy.
Symptoms
NASH is usually a silent disease with few or no symptoms. Patients
generally feel well in the early stages and only begin to have
symptoms' such as fatigue, weight loss, and weakness, once the disease is
more advanced or cirrhosis develops. The progression of NASH can take
years, even decades. The process can stop and, in some cases, reverse
on its own without specific therapy. Or NASH can slowly worsen, causing
scarring or "fibrosis" to appear and accumulate in the liver. As
fibrosis worsens, cirrhosis develops; the liver becomes seriously
scarred, hardened, and unable to function normally. Not every person
with NASH develops cirrhosis, but once serious scarring or cirrhosis is
present, few treatments can halt the progression. A person with
cirrhosis experiences fluid retention, muscle wasting, bleeding from
the intestines, and liver failure. Liver transplantation is the only
treatment for advanced cirrhosis with liver failure, and
transplantation is increasingly performed in people with NASH. NASH
ranks as one of the major causes of cirrhosis in America, behind
hepatitis C and alcoholic liver disease.
Stages of liver damage.
Causes
Although NASH has become more common, its underlying cause is still
not clear. It most often occurs in persons who are middle-aged and
overweight or obese. Many patients with NASH have elevated blood
lipids, such as cholesterol and triglycerides, and many have diabetes
or pre-diabetes, but not every obese person or every patient with
diabetes has NASH. Furthermore, some patients with NASH are not obese,
do not have diabetes, and have normal blood cholesterol and lipids.
NASH can occur without any apparent risk factor and can even occur in
children. Thus, NASH is not simply obesity that affects the liver.
While the underlying reason for the liver injury that causes NASH is not known, several factors are possible candidates:
insulin resistance
release of toxic inflammatory proteins by fat cells (cytokines)
oxidative stress (deterioration of cells) inside liver cells
Treatment
Currently, no specific therapies for NASH exist. The most important recommendations given to persons with this disease are to
reduce their weight (if obese or overweight)
follow a balanced and healthy diet
increase physical activity
avoid alcohol
avoid unnecessary medications
These are standard recommendations, but they can make a difference.
They are also helpful for other conditions, such as heart disease,
diabetes, and high cholesterol.
A major attempt should be made to lower body weight into the healthy
range. Weight loss can improve liver tests in patients with NASH and
may reverse the disease to some extent. Research at present is focusing
on how much weight loss improves the liver in patients with NASH and
whether this improvement lasts over a period of time.
People with NASH often have other medical conditions, such as
diabetes, high blood pressure, or elevated cholesterol. These
conditions should be treated with medication and adequately controlled;
having NASH or elevated liver enzymes should not lead people to avoid
treating these other conditions.
Experimental approaches under evaluation in patients with NASH
include antioxidants, such as vitamin E, selenium, and betaine. These
medications act by reducing the oxidative stress that appears to
increase inside the liver in patients with NASH. Whether these
substances actually help treat the disease is not known, but the
results of clinical trials should become available in the next few
years.
Another experimental approach to treating NASH is the use of newer
antidiabetic medications, even in persons without diabetes. Most
patients with NASH have insulin resistance, meaning that the insulin
normally present in the bloodstream is less effective for them in
controlling blood glucose and fatty acids in the blood than it is for
people who do not have NASH. The newer antidiabetic medications make
the body more sensitive to insulin and may help reduce liver injury in
patients with NASH. Studies of these medications, including metformin,
rosiglitazone, and pioglitazone, are being sponsored by the National
Institutes of Health and should answer the question of whether these
medications are beneficial in NASH.
Points to Remember
Nonalcoholic steatohepatitis (NASH) is fat in the liver, with inflammation and damage.
NASH occurs in people who drink little or no alcohol and affects 2 to 5 percent of Americans, especially people who are middle-aged and overweight or obese.
NASH can occur in children.
People who have NASH may feel well and may not know that they have a liver disease.
NASH can lead to cirrhosis, a condition in which the liver is permanently damaged and cannot work properly.
Fatigue can occur at any stage of NASH.
Weight loss and weakness may begin once the disease is advanced or cirrhosis is present.
NASH may be suspected if blood tests show high levels of liver enzymes or if scans show fatty liver.
NASH is diagnosed by examining a small piece of the liver taken through a needle, a procedure called biopsy.
People who have NASH should reduce their weight, eat a balanced diet, engage in physical activity, and avoid alcohol and unnecessary medications.
No specific therapies for NASH exist. Experimental therapies being studied include antioxidants and antidiabetes medications.
Reprinted from National Digestive Diseases Information Clearinghouse.
For More Information
American Liver Foundation (ALF)
75 Maiden Lane
Suite 603
New York, NY 10038
Phone: 1-800-GO-LIVER (465-4837), 1-888-4HEP-USA (443-7872), or 212-668-1000
Fax: 212-483-8179
Email: info@liverfoundation.org
Internet: www.liverfoundation.org