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Magill's Medical Guide 4th rev. ed.
Nonalcoholic Steatohepatitis (NASH)

Also Known As: Fatty liver, nonalcoholic fatty liver disease (NAFLD)

Anatomy or System Affected: Endocrine system, gastrointestinal system, liver

Specialties and Related Fields: Endocrinology, family medicine, gastroenterology, internal medicine, pediatrics

Definition: Fatty inflammation of the liver that is not caused by alcohol.

Key Terms
central obesity: excessive abdominal fat

hyperlipidemia: an excess of fat or lipids in the blood

insulin resistance syndrome: a condition characterized by the decreased sensitivity to insulin that is associated with central obesity, metabolic syndrome, and diabetes

metabolic syndrome: a condition defined by the presence of three or more of high blood pressure, abdominal obesity, high triglycerides, low high-density lipoproteins (HDL) cholesterol, and abnormal fasting blood sugar

nonsteroidal anti-inflammatory drugs (NSAIDs): a class of medications for inflammation that do not contain steroids; includes aspirin and ibuprofen

Causes and Symptoms
The liver is a complex organ located in the right upper abdomen. It is responsible for converting carbohydrates, fats, and proteins from food into usable forms for the body. It also manufactures cholesterol, stores sugar, and metabolizes certain medications and chemicals. Nonalcoholic steatohepatitis (NASH) is characterized by the storage of excess fat in the liver with associated inflammation. The cause of this disorder is not completely understood. The accumulation of excess fat in the liver is related to the body's inability to use its own insulin, a common problem found in adults and children with central obesity. NASH is also found in individuals with other medical conditions, such as diabetes, metabolic syndrome, high blood pressure, and hyperlipidemia. Other causes of excess fat storage are certain medications, exposure to occupational toxins, and some surgical procedures. The excess fat causes damage to the cells of the liver that is similar to the damage caused by excess alcohol intake.

The majority of people with NASH have no symptoms, and the disorder is suspected from liver function tests. Studies have shown, however, that elevated liver enzymes do not always occur in individuals with NASH. If symptoms are present, then they may include fatigue or mild discomfort in the upper right side of the abdomen. The liver may be enlarged. Fatty liver may be identified on ultrasound, but a biopsy of the liver must be performed in order to determine the extent of the disorder. A liver biopsy is a minor surgical procedure that is performed by inserting a large needle into the liver through a small incision and removing cells for evaluation under the microscope. The disorder may range from inflammation of the liver to cirrhosis, a chronic, progressive disease with extensive scarring of the liver that causes destruction of liver cells. If the destruction advances, then the liver loses the ability to function. Severe liver disease occurs in approximately 20 percent of those with NASH.

Treatment and Therapy
Treatment goals include the identification and treatment of associated conditions and the reduction of insulin resistance. Adopting a healthy lifestyle is the primary treatment for NASH. Those who are overweight are encouraged to lose weight gradually and to exercise. Triglyceride and cholesterol levels should be kept within normal limits. Strict blood sugar control is indicated for diabetics with NASH. A small study of children with NASH found that daily vitamin E reduced abnormal liver enzymes. Another small study found that daily treatment for one year with a natural bile acid, ursodeoxycholic acid (Actigall or Urso), improved liver function tests and seemed to have a protective effect on the liver. Follow-up studies, however, did not show these improvements. Two insulin-sensitizing drugs have had mixed results in small studies. Liver inflammation was significantly improved in one study, but both drug studies had subjects withdrawn as a result of liver toxicity. Lipid-lowering drug studies have also shown some improvement in blood liver function tests, but not in the follow-up biopsy tests for inflammation and damage.

It is generally recommended that individuals with NASH avoid alcohol and certain medications, such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), that may further damage the liver. If the individual develops severe cirrhosis, then a liver transplant may be necessary to avoid death.

Perspective and Prospects
In 1958, fatty liver disease was first identified in a small group of obese individuals. It was not until the 1970's, when surgeons were performing gastric bypass surgeries for the treatment of obesity, that the disorder was reported. In 1980, the term nonalcoholic steatohepatitis was coined to describe a small group of patients at Mayo Clinic who had liver biopsy findings similar to those with alcoholic liver disease. Since 2000, pediatricians have reported the presence of NASH in obese children, as well as in children with other endocrine disorders. The increase in obesity and diabetes in the United States has been linked to the increasing numbers of individuals diagnosed with NASH.

Diagnosis is confirmed with a liver biopsy, but controversy over this procedure exists, given the possible risks and the lack of treatment options available for the disorder. Recently, efforts to establish a noninvasive method for diagnosis have been made. Ultrasound and abdominal computed tomography (CT) scans are often used but have not been able to distinguish the extent of the disease process adequately. Newer X-ray techniques and more specific laboratory blood analyses are being investigated as diagnostic methods.

Drug therapy continues to be investigated after promising pilot studies. Further study is also needed in the area of the disease process and its potential for progression in some individuals.

Amy Webb Bull, D.S.N., A.P.N.

See Also
Abdomen; Abdominal disorders; Alcoholism; Cholesterol; Cirrhosis; Diabetes mellitus; Gastroenterology; Gastroenterology, pediatric; Gastrointestinal disorders; Gastrointestinal system; Hypercholesterolemia; Hyperlipidemia; Inflammation; Insulin resistance syndrome; Internal medicine; Liver; Liver disorders; Liver transplantation; Metabolic syndrome; Metabolism; Obesity; Obesity, childhood; Transplantation.

Further Information
Adams, L. A., and P. Angulo. "Treatment of Non-alcoholic Fatty Liver Disease." Postgraduate Medicine Journal, 82 (May, 2006): 315-322.

Harrison, Stephen A., and Adrian M. Di Bisceglie. "Advances in the Understanding and Treatment of Nonalcoholic Fatty Liver Disease." Drugs 63, no. 22 (2003): 2379-2394.

"Liver Disease: Fat Inflames the Liver." Harvard Health Letter 26 (February, 2001): 4.

Nakajima, Kenichirou, et al. "Pediatric Nonalcoholic Steatohepatitis Associated with Hypopituitarism." Journal of Gastroenterology 40, no. 3 (March, 2005): 312-315.

Porth, Carol Mattson. "Disorders of Hepatobiliary and Exocrine Pancreas Function." In Pathophysiology: Concepts of Altered Health States. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2005.