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INTRODUCTION — Nonalcoholic fatty liver disease (NAFLD) is a medical condition that is characterized by the buildup of fat (called fatty infiltration) in the liver (figure 1). There are two types of NAFLD:
●Nonalcoholic fatty liver (NAFL), a generally benign condition in which there is fatty infiltration but no inflammation
●Nonalcoholic steatohepatitis (NASH), in which there is fatty infiltration along with liver inflammation
Alcohol use disorder and other conditions can also lead to liver problems. To be diagnosed with either form of NAFLD, a person must not have a history of heavy alcohol use or another problem that might be causing the liver condition (such as hepatitis C).
NONALCOHOLIC FATTY LIVER — Nonalcoholic fatty liver (NAFL) is a generally benign condition that has become increasingly common in the United States and Western Europe as weight gain and obesity have become more common. It is now the most common chronic liver disorder in the United States and other western industrialized countries.
In NAFL, the liver functions normally and there are no symptoms. NAFL is often found when a person has imaging tests of the abdomen for other reasons (such as an ultrasound being done to look for gallstones). If you are overweight, losing weight can reduce the amount of fat in your liver. Aside from this, there is no treatment for NAFL, although you should be vaccinated against hepatitis A and B (which can damage your liver) if you are not already immune.
Many people with NAFL never develop inflammation (NASH), although some do.
NONALCOHOLIC STEATOHEPATITIS — Nonalcoholic steatohepatitis (NASH) is a condition that causes inflammation and accumulation of fat and scar tissue in the liver. Although a similar condition can occur in people who have alcohol use disorder, 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 (see 'Associated conditions' below). This combination of disorders if often called "metabolic syndrome."
It is not clear how many people have NASH because it causes no symptoms. However, NASH is diagnosed in about 3 to 5 percent of people in the United States who have a liver biopsy (which may be done to check for a number of different liver conditions). 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 females than in males.
Treatment of NASH focuses on controlling some of the medical conditions associated with it (such as diabetes and obesity) and monitoring for progression. Some studies suggest that people who drink coffee have a lower risk of developing liver scarring, and some researchers have suggested that moderate coffee consumption may be beneficial. As with nonalcoholic fatty liver disease, people with NASH should be vaccinated against hepatitis A and B if they are not already immune.
Associated conditions — 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 have obesity.
●Diabetes – Up to 75 percent of people with NASH have type 2 diabetes. This is a disorder that disrupts the way your body uses sugar. Normally, sugar gets into the cells with the help of a hormone called insulin, which is made in the pancreas. In people with type 2 diabetes, the body stops responding to normal or high levels of insulin, which causes sugar to build up in the blood; eventually, the pancreas becomes unable to produce enough insulin. (See "Patient education: Type 2 diabetes: 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 education: High cholesterol and lipids (Beyond the Basics)".)
●Insulin resistance – Insulin resistance refers to a state in which the body does not respond adequately to insulin, but the person does not yet have type 2 diabetes. This often occurs in people with hyperlipidemia who have obesity; this group of symptoms is known as the metabolic syndrome and is frequently seen in people with NASH. (See "Patient education: Type 2 diabetes: Overview (Beyond the Basics)".)
●Drugs and toxins – Several drugs used to treat other medical conditions have been linked to NASH, including amiodarone (brand names: Corderone, Pacerone), tamoxifen (brand names: Nolvadex, Tamone), perhexiline maleate (brand name: Pexhid), steroids (eg, prednisone, hydrocortisone), and synthetic estrogens. Certain pesticides have also been linked to NASH.
Symptoms — Most people with NASH have no symptoms. Rarely, NASH is found (after testing) 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.
Diagnosis — NASH is most often discovered following routine blood tests. 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 [MRI]) 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 may be required to confirm NASH if other causes of liver disease cannot be excluded.
Liver function tests — Blood tests to measure 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 education: Hepatitis A (Beyond the Basics)" and "Patient education: Hepatitis B (Beyond the Basics)" and "Patient education: Hepatitis C (Beyond the Basics)".)
Liver biopsy and fibroscan — Although other tests may suggest a diagnosis of NASH, sometimes a liver biopsy is required to confirm it. A liver biopsy may be needed if other causes of liver disease cannot be ruled out with standard blood and imaging tests. A liver biopsy can also help determine the severity of inflammation, detect liver scarring (called "fibrosis" or, in severe cases, "cirrhosis"), 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 education: Liver biopsy (Beyond the Basics)".)
Fibroscan is a noninvasive test that uses ultrasound to determine how "stiff" the liver is. This stiffness can then be used to estimate how much scarring there is in the liver and to determine if cirrhosis has developed. Where available, fibroscan is an alternative to liver biopsy for detecting liver scarring.
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 — Losing weight can help to reduce levels of liver enzymes and insulin and can improve quality of life. Weight loss should be gradual (for example 1 to 2 lbs per week) since rapid weight loss has been associated with worsening of liver disease. A health care provider or nutritionist can provide an individualized weight loss plan. (See "Patient education: Losing weight (Beyond the Basics)".)
People with NASH, early cirrhosis, and obesity who undergo bariatric (weight loss) surgery often have improvement of their liver disorder. (See "Patient education: Weight loss surgery and procedures (Beyond the Basics)".)
Treatment of insulin resistance — Several drugs are available for people with insulin resistance, and they are being studied in people with NASH. Their role is not yet proven.
More information about treatments for insulin resistance is available in a separate topic review. (See "Patient education: Type 2 diabetes: Treatment (Beyond the Basics)", section on 'Thiazolidinediones'.)
Vitamin E — For people with severe forms of NASH who do not also have diabetes or heart disease, health care providers sometimes recommend supplements of vitamin E. There is some evidence that vitamin E might reduce some of the liver damage that occurs as part of NASH, but the evidence is weak, and there is also evidence that high-doses of vitamin E supplements increase the risk of death. Do not take vitamin E unless your health care provider recommends it.
Avoid alcohol — People with NASH should avoid drinking alcohol, because it can worsen liver disease.
Prognosis — NASH is typically a chronic, life-long condition. It is difficult to predict the progression 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 many 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, in some people, NASH gets worse over time. The most serious complication of NASH is cirrhosis, which is when the liver becomes severely scarred. Cirrhosis does not always cause symptoms, but when symptoms do occur, they can include swelling in the legs, trouble breathing, or fatigue. Older people with diabetes may be at increased risk for developing cirrhosis. (See "Patient education: Cirrhosis (Beyond the Basics)".)
People with NASH often have metabolic syndrome (insulin resistance, obesity, and hyperlipidemia) (see 'Associated conditions' above). Metabolic syndrome puts you at increased risk for heart disease. The good news is that the treatments for NASH (particularly weight loss) also help treat the other problems that are part of the metabolic syndrome.
WHERE TO GET MORE INFORMATION — Your health care 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 health care 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 education: Nonalcoholic fatty liver disease (The Basics)
Patient education: 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 education: Type 2 diabetes: Overview (Beyond the Basics)
Patient education: High cholesterol and lipids (Beyond the Basics)
Patient education: Hepatitis A (Beyond the Basics)
Patient education: Hepatitis B (Beyond the Basics)
Patient education: Hepatitis C (Beyond the Basics)
Patient education: Liver biopsy (Beyond the Basics)
Patient education: Losing weight (Beyond the Basics)
Patient education: Type 2 diabetes: Treatment (Beyond the Basics)
Patient education: 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
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
Noninvasive assessment of hepatic fibrosis: Overview of serologic tests and imaging examinations
The following organizations also provide reliable health information.
●National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
●National Institute of Diabetes and Digestive and Kidney Diseases
●The American Association for the Study of Liver Diseases
●The American Liver Foundation
