Patient information: Nonalcoholic steatohepatitis (NASH)

INTRODUCTION

Nonalcoholic steatohepatitis (NASH) is a condition that causes inflammation and accumulation of fat and fibrous tissue in the liver (figure 1). Although a similar condition can occur in people who abuse alcohol, NASH occurs in those who do drink little to no alcohol. The exact cause of NASH is unknown. However, it is seen more frequently in people with certain medical conditions such as diabetes, obesity, and insulin resistance.

It is not clear how many people have NASH because it causes no symptoms. However, NASH is diagnosed in about 7 to 9 percent of people in the United States who have a liver biopsy. Most people are between the ages of 40 and 60 years, although the condition can also occur in children over the age of 10 years. NASH is seen more often in women than in men.

The cause of NASH is not clear, although research is ongoing in an attempt to find effective treatments. At the present time, treatment of NASH focuses on controlling some of the medical conditions associated with it (such as diabetes and obesity) and monitoring for progression.

CONDITIONS ASSOCIATED WITH NONALCOHOLIC STEATOHEPATITIS

Although the cause of NASH is unknown, it is most frequently seen in people with one of more of the following conditions.

• Obesity — More than 70 percent of people with NASH are obese. Most obese people with NASH are between 10 and 40 percent heavier than their ideal body weight.
• Diabetes — Up to 75 percent of people with NASH have type 2 diabetes. (See "Patient information: Diabetes mellitus type 2: Overview".)

• Hyperlipidemia — About 20 to 80 percent of people with NASH have hyperlipidemia (high blood triglyceride levels and/or high blood cholesterol levels). (See "Patient information: High cholesterol and lipids (hyperlipidemia)".)

• Insulin resistance — Insulin resistance refers to a state in which the body does not respond adequately to insulin. Insulin resistance often occurs in people with hyperlipidemia who are obese; this group of symptoms is known as the metabolic syndrome and is frequently seen in people with NASH. (See "Patient information: Diabetes mellitus type 2: Overview".)

• Abdominal surgery — Several types of abdominal operations have been linked to NASH. These include surgical removal of large portions of the small intestine, gastric bypass surgery, surgery of the gall bladder and pancreas, and surgery used to bypass parts of the small intestine.
• Drugs and toxins — Several drugs used to treat medical conditions have been linked to NASH, including amiodarone (Corderone®, Pacerone®), tamoxifen (Nolvadex®, Tamone®), perhexilene maleate (Pexhid®), steroids (eg, prednisone, hydrocortisone), and synthetic estrogens. Pesticides that are toxic to cells have also been linked to NASH.
• Other conditions — Certain other medical conditions have also been linked to NASH. These conditions include Wilson's disease (a hereditary condition that affects copper levels), Weber-Christian disease, abetalipoproteinemia (a rare congenital disorder that affects the ability to digest fat), and diverticula (outpouchings) of the small intestine.

NONALCOHOLIC STEATOHEPATITIS SYMPTOMS

Most people with NASH have no symptoms. Rarely, NASH is diagnosed in people with fatigue, a general feeling of being unwell, and a vague discomfort in their upper right abdomen, although it is not clear if these symptoms are related to NASH.

NONALCOHOLIC STEATOHEPATITIS DIAGNOSIS

NASH is most often discovered during routine laboratory testing. Additional tests help confirm the presence of NASH and rule out other types of liver disease. Imaging tests (such as ultrasound, CT scan, or magnetic resonance imaging) may reveal fat accumulation in the liver but cannot differentiate NASH from other causes of liver disease that have a similar appearance. A liver biopsy is required to confirm NASH.

Liver function tests — Blood tests to measure the liver function measure levels of substances produced or metabolized by the liver. These levels can help to diagnose NASH and differentiate NASH from alcoholic hepatitis. Levels of two liver enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) are elevated in about 90 percent of people with NASH.

Other blood tests — Additional blood tests are useful for ruling out other causes of liver disease. These usually include tests for viral hepatitis (hepatitis A, B, or C), and may include tests for less common cause of liver disease. (See "Patient information: Hepatitis A" and "Patient information: Hepatitis B" and "Patient information: Hepatitis C".)

Liver biopsy — Although other tests may suggest a diagnosis of NASH, liver biopsy is required to confirm it. A liver biopsy is also helpful for determining the severity of NASH and may provide clues about the future course of the condition. The procedure involves collecting a small sample of liver tissue, which is sent to a laboratory for microscopic examination and biochemical testing. More detailed information about liver biopsies is available in a separate topic review. (See "Patient information: Liver biopsy".)

NONALCOHOLIC STEATOHEPATITIS TREATMENT

At this time, there is no treatment to cure NASH. Treatment aims to control the conditions that are associated with NASH, such as obesity, diabetes, and hyperlipidemia. Several experimental treatments are being studied with drugs that treat insulin resistance.

Weight loss — Weight reduction can help to reduce levels of liver enzymes, insulin, and can improve quality of life. Weight loss should be gradual (no more than 3.5 lbs or 1.6 kg per week) since rapid weight loss has been associated with worsening of liver disease. A healthcare provider or nutritionist can provide an individualized weight loss plan. (See "Patient information: Weight loss treatments".)

Treatment of insulin resistance — Several drugs are available for people with insulin resistance, including rosiglitazone (Avandia®), pioglitazone (Actos®) and metformin (glucophage®). These medications are being studied in patients with NASH, with one and two year studies showing improvement in ALT and AST levels and liver histology.

However, liver enzyme tests appear to return to pretreatment levels shortly after these drugs are stopped. Hence, effective treatment may require that the medication be taken for many years, perhaps a lifetime. In addition, there is a concern that one of the drugs, rosiglitazone, may cause heart damage. Currently, treatment of insulin resistance in NASH is still experimental and unproven. The results of long-term studies of these medications are expected within the next few years.

More information about treatments for insulin resistance is available in a separate topic review. (See "Patient information: Diabetes mellitus type 2: Treatment", in the section called "Thiazolidinediones").

Miscellaneous drugs — Several new drugs are being tested in patients with NASH but none has yet proven to be beneficial in large, long-term studies.

NONALCOHOLIC STEATOHEPATITIS PROGNOSIS

NASH is typically a chronic condition (ie, it persists for many years). It is difficult to predict the course of NASH in an individual. Few factors have been useful in predicting the course of this condition, although features in the liver biopsy can be helpful.

The good news is most people with NASH will not develop serious liver problems. One study showed that most people with NASH live as long as those without it. Furthermore, liver function tests are stable over time in most people with NASH.

However, NASH can progress in some people. One study that tracked liver damage over time showed that the condition improved in about 3 percent of people, remained stable in 54 percent of people, and worsened in 43 percent of people [1].

The most serious complication of NASH is cirrhosis, which occurs when the liver becomes severely scarred. In one study, between 8 and 26 percent of people with NASH developed cirrhosis [1]. Older diabetic women may be at increased risk. Complications of cirrhosis can include internal bleeding, fluid accumulation in the legs and abdomen, mental confusion, and jaundice, which may ultimately require liver transplantation. (See "Patient information: Cirrhosis".)

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include:

Patient Level Information:
Patient information: Diabetes mellitus type 2: Overview
Patient information: High cholesterol and lipids (hyperlipidemia)
Patient information: Hepatitis A
Patient information: Hepatitis B
Patient information: Hepatitis C
Patient information: Liver biopsy
Patient information: Weight loss treatments
Patient information: Diabetes mellitus type 2: Treatment
Patient information: Cirrhosis

Professional Level Information:
Immunizations for patients with chronic liver disease
Nonalcoholic steatohepatitis
Pathogenesis of nonalcoholic fatty liver disease

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

• National Library of Medicine

      (www.nlm.nih.gov/medlineplus/healthtopics.html)

• National Institute of Diabetes and Digestive and Kidney Diseases

      (www.niddk.nih.gov)

• The American Association for the Study of Liver Diseases

      (www.aasld.org)

• The American Liver Foundation

      (www.liverfoundation.org)

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