There are two types of fatty infiltration of the liver: simple (or benign) fatty infiltration and nonalcoholic steatohepatitis (NASH).
Simple fatty liver is a benign condition that has become increasingly common in the United States and Western Europe as weight gain and frank obesity have become more common. In fatty liver, the liver functions normally and looks normal under the microscope, except for accumulations of fat in storage organelles in the liver (vacuoles). Liver blood tests are either normal, or there may be slight increases in two of the enzymes made by the liver, the serum ALT (alanine aminotransferase) and/or the serum AST (aspartate aminotransferase). The diagnosis may be confirmed with a right upper quadrant ultrasound examination. Liver biopsy is rarely necessary. Aside from losing weight, there is no other treatment. The only known downside is that patients with fatty livers are excluded as liver donors in both deceased (cadaveric) and live donor liver transplantation.
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 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. This combination of disorders if often called the metabolic syndrome.
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 (Beyond the Basics)".)
- 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) (Beyond the Basics)".)
- 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 (Beyond the Basics)".)
- Drugs and toxins — Several drugs used to treat medical conditions have been linked to NASH, including amiodarone (Corderone®, Pacerone®), tamoxifen (Nolvadex®, Tamone®), perhexiline maleate (Pexhid®), steroids (eg, prednisone, hydrocortisone), and synthetic estrogens. Pesticides that are toxic to cells have also been linked to NASH.
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 causes of liver disease. (See "Patient information: Hepatitis A (Beyond the Basics)" and "Patient information: Hepatitis B (Beyond the Basics)" and "Patient information: Hepatitis C (Beyond the Basics)".)
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 (Beyond the Basics)".)
NONALCOHOLIC STEATOHEPATITIS TREATMENT
There is no cure for 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 (Beyond the Basics)".)
Treatment of insulin resistance — Several drugs are available for people with insulin resistance, and they are being studied in patients with NASH. Their role is not yet proven.
More information about treatments for insulin resistance is available in a separate topic review. (See "Patient information: Diabetes mellitus type 2: Treatment (Beyond the Basics)", section on '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 .
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 . Older diabetic women may be at increased risk. (See "Patient information: Cirrhosis (Beyond the Basics)".)
WHERE TO GET MORE INFORMATION
Your healthcare provider is the best source of information for questions and concerns related to your medical problem.
This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.
Patient level information — UpToDate offers two types of patient education materials.
The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.
Patient information: Nonalcoholic steatohepatitis (NASH) (The Basics)
Patient information: Cirrhosis (The Basics)
Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.
Patient information: Diabetes mellitus type 2: Overview (Beyond the Basics)
Patient information: High cholesterol and lipids (hyperlipidemia) (Beyond the Basics)
Patient information: Hepatitis A (Beyond the Basics)
Patient information: Hepatitis B (Beyond the Basics)
Patient information: Hepatitis C (Beyond the Basics)
Patient information: Liver biopsy (Beyond the Basics)
Patient information: Weight loss treatments (Beyond the Basics)
Patient information: Diabetes mellitus type 2: Treatment (Beyond the Basics)
Patient information: Cirrhosis (Beyond the Basics)
Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.
Immunizations for patients with chronic liver disease
Natural history and management of nonalcoholic fatty liver disease in adults
Pathogenesis of nonalcoholic fatty liver disease
Epidemiology, clinical features, and diagnosis of nonalcoholic fatty liver disease in adults
The following organizations also provide reliable health information.
- National Library of Medicine
- National Institute of Diabetes and Digestive and Kidney Diseases
- The American Association for the Study of Liver Diseases
- The American Liver Foundation