Nonalcoholic
 

Steatohepatitis
 

National Digestive Diseases Information Clearinghouse 

National 

Institute of 

Diabetes and 

Digestive 

and Kidney 

Diseases 

NATIONAL 

INSTITUTES 

OF HEALTH 

U.S. Department 

of Health and 

Human Services 

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. 

Liver 

Gallbladder 

Cystic duct 

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. 

Pancreas 

Stomach 

Common bile duct 

Duodenum 

Common hepatic duct 

Pancreatic duct 

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 

A small, slender core of tissue is 

removed with a biopsy needle and 

looked at through a microscope. 

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 

2 Nonalcoholic Steatohepatitis 
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. 

Fatty liver Liver fibrosis Cirrhosis 

Deposits of fat Scar tissue forms. Scar tissue 

cause liver More liver cell makes liver hard 

enlargement. injury occurs. and unable to 

work properly. 

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 

3	 Nonalcoholic Steatohepatitis 
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. 

Hope Through Research 

What is most needed in the management 

of NASH is more research to better understand the liver injury found in this disease. 

When the pathways that lead to the injury 

are fully known, safe and effective means 

can be developed to reverse these pathways 

and help patients with NASH. Recent 

breakthroughs in mapping the human 

genome and uncovering the individual 

steps by which insulin and other hormones 

regulate blood glucose and fat could provide the necessary clues. 

The National Institute of Diabetes and 

Digestive and Kidney Diseases funds the 

NASH Clinical Research Network, which 

comprises eight clinical centers located 

throughout the United States and a coordinating center at Johns Hopkins University. 

The NASH network researches the nature 

and underlying cause of NASH and conducts clinical studies on prevention and 

treatment. More information on the 

NASH Clinical Research Network and 

the locations of the clinical centers are 

available at www.jhucct.com/nash/. 

4	 Nonalcoholic Steatohepatitis 
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 middle­aged 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.

For More Information

American Liver Foundation 

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

You may also find additional information about this

topic by visiting MedlinePlus at www.medlineplus.gov.

This publication may contain information about 

medications.  When prepared, this publication

included the most current information available.  

For updates or for questions about any medications,

contact the U.S. Food and Drug Administration 

toll­free at 1–888–INFO–FDA (1–888–463–6332) 

or visit www.fda.gov.  Consult your doctor for more

information.

5	 Nonalcoholic Steatohepatitis
National Digestive Diseases 

Information Clearinghouse 

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Phone: 1–800–891–5389 

Fax: 703–738–4929 

Email: nddic@info.niddk.nih.gov 

Internet: www.digestive.niddk.nih.gov 

The National Digestive Diseases Information 

Clearinghouse (NDDIC) is a service of the 

National Institute of Diabetes and Digestive 

and Kidney Diseases (NIDDK). The NIDDK 

is part of the National Institutes of Health of 

the U.S. Department of Health and Human 

Services. Established in 1980, the Clearinghouse provides information about digestive 

diseases to people with digestive disorders 

and to their families, health care professionals, 

and the public. The NDDIC answers inquiries, 

develops and distributes publications, and 

works closely with professional and patient 

organizations and Government agencies to 

coordinate resources about digestive diseases. 

Publications produced by the Clearinghouse 

are carefully reviewed by both NIDDK scientists and outside experts. The original version 

of this fact sheet was reviewed by Anna Mae 

Diehl, M.D., Johns Hopkins University; and 

Brent Tetre, M.D., St. Louis University. 

This publication is not copyrighted. The 

Clearinghouse encourages users of this fact 

sheet to duplicate and distribute as many 

copies as desired. 

This fact sheet is also available at 

www.digestive.niddk.nih.gov. 

U.S. DEPARTMENT OF HEALTH 

AND HUMAN SERVICES 

National Institutes of Health 

NIH Publication No. 07–4921 

November 2006