Patient education: Nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH) (Beyond the Basics)
- Sanjiv Chopra, MD, MACP
Sanjiv Chopra, MD, MACP
- Editor-in-Chief — Gastroenterology and Hepatology
- Section Editor — General Hepatology; Gallbladder and Biliary Tract Disease
- Professor of Medicine
- Harvard Medical School
- Senior Consultant in Hepatology
- James Tullis Firm Chief
- Beth Israel Deaconess Medical Center
Nonalcoholic fatty liver disease (NAFLD) is a medical condition that is characterized by the buildup of fat (called fatty infiltration) in the liver. There are two types of fatty infiltration of the liver:
●Nonalcoholic fatty liver (NAFL) is a generally benign condition in which the fatty infiltration is simple and there is no inflammation
●Nonalcoholic steatohepatitis (NASH) in which there is fatty infiltration along with liver inflammation (steatohepatitis)
To be diagnosed with either form, a person cannot have a history of heavy alcohol use or another problem that might be causing the liver condition (such as an infection with the hepatitis C virus).
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 cause of liver disorder in the United States and other Western industrialized countries. In fatty liver, the liver functions normally and looks normal under the microscope, except for accumulations of fat within cells. NAFL is often detected when imaging tests of the abdomen are obtained for other reasons (such as an ultrasound being done to look for gallstones). 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. If the liver blood tests are very elevated or if there are other signs of liver disease (such as yellowing of the skin), then a liver biopsy may be recommended to look for other problems such as nonalcoholic steatohepatitis (NASH). Aside from losing weight, there is no other treatment, though people with liver disease should be vaccinated against hepatitis A and B if they are not already immune.
Patients with fatty livers are excluded as liver donors in both deceased (cadaveric) and live donor liver transplantation. Most patients with NAFL never develop inflammation (NASH), although some do.
Nonalcoholic steatohepatitis (NASH) is a condition that causes inflammation and accumulation of fat and fibrous (scar) tissue in the liver (figure 1). Liver enzyme levels in the blood may be more elevated than the mild elevations seen with nonalcoholic fatty liver (NAFL). 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 3 to 5 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. Some studies suggest 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.
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 education: 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 education: 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 education: 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 (brand names: Corderone, Pacerone), tamoxifen (brand names: Nolvadex, Tamone), perhexiline maleate (brand name: 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 [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 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 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 (fibrosis or, when severe, 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.
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 education: 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 education: Diabetes mellitus type 2: 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, healthcare 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 healthcare provider recommends it.
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 education: Cirrhosis (Beyond the Basics)".)
People with NASH often have the metabolic syndrome (insulin resistance, obesity, and hyperlipidemia). The metabolic syndrome puts people 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 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.
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: Diabetes mellitus type 2: Overview (Beyond the Basics)
Patient education: High cholesterol and lipids (hyperlipidemia) (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: Weight loss treatments (Beyond the Basics)
Patient education: Diabetes mellitus type 2: 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
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
Noninvasive assessment of hepatic fibrosis: Overview of serologic and radiographic tests
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
- Powell EE, Cooksley WG, Hanson R, et al. The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years. Hepatology 1990; 11:74.
- Angelico F, Burattin M, Alessandri C, et al. Drugs improving insulin resistance for non-alcoholic fatty liver disease and/or non-alcoholic steatohepatitis. Cochrane Database Syst Rev 2007; :CD005166.
- Musso G, Gambino R, Cassader M, Pagano G. A meta-analysis of randomized trials for the treatment of nonalcoholic fatty liver disease. Hepatology 2010; 52:79.
- Pascale A, Pais R, Ratziu V. An overview of nonalcoholic steatohepatitis: past, present and future directions. J Gastrointestin Liver Dis 2010; 19:415.
All topics are updated as new information becomes available. Our peer review process typically takes one to six weeks depending on the issue.