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Medical Author:

Michel Mendler, M D

Medical Editor:

Leslie J. Schoenfield, MD, PhD

Leslie J. Schoenfield, MD, PhD

Dr. Schoenfield served as associate professor of medicine and consultant in gastroenterology on the faculty of the Mayo Clinic for seven years. He became a professor of medicine in residence at UCLA from 1972 to 1999 (now emeritus). He was the director of gastroenterology at Cedars-Sinai Medical Center in Los Angeles for 25 years, where he received the chief resident's teaching award, the president's award, and the pioneer of medicine award.

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In this Article

• What are Fatty Liver, NAFLD, and NASH?
• What is the NAFLD spectrum?
• Are there other causes of fat accumulation in the liver?
• How long have we known about NAFLD and NASH?
• How common are NAFLD and NASH and who are at risk?
• Why is information on the number of cases limited?
• What is the BMI and how does it relate to NAFLD and NASH?
• What are the estimated numbers of cases of NAFLD and NASH?
• What causes NAFLD and NASH?
• What is insulin resistance and how does it relate to NAFLD?
• How does insulin resistance relate to NASH?
• What else besides insulin resistance contributes to NASH?
• What are the symptoms of NAFLD and NASH?
• What are the complications of NASH?
• How are NAFLD and NASH diagnosed?
• What are the difficulties in evaluating NAFLD and NASH?
• What are the diagnostic clues for severe NASH?
• What can a liver biopsy show and when should it be done?
• How are NAFLD and NASH treated?
• What is the future of NAFLD and NASH?
• NAFLD and NASH At A Glance
• Patient Comments: Fatty Liver - Causes
• Patient Comments: Fatty Liver - How Was Diagnosis Established
• Fatty Liver Glossary
• Fatty Liver Index
• Find a local Gastroenterologist in your town

What is the future of NAFLD and NASH?

NAFLD is probably the single most common liver abnormality in the United States. It appears to be linked directly to the growing epidemic of obesity in adults as well as in children. Thus, in a sense, NAFLD is a sell-inflicted liver disease, much like alcoholic liver disease. But only a minority of patients who are obese or diabetic will develop severe liver disease and this is most likely determined genetically. In addition, increasing evidence suggests that obesity and diabetes can worsen alcoholic liver disease and liver disease due to HCV.

For these reasons, basic science researchers, liver specialists (hepatologists), nutritionists, and hormone specialists (endocrinologists) are combining their efforts to better understand and contain this process that has been recognized for only the past 30 years.

Research into the genetics of this process will reveal the pathways that lead to severe disease and help to recognize those patients most at risk. Clinical research will help us understand the natural clinical history of this process and perhaps identify predictors of outcome. Basic science research will be aimed at understanding how the disease comes about and the processes involved. This knowledge then may lead to the development of specific treatments. Currently, small trials are ongoing that involve insulin-sensitizing agents, such as metformin (Glucophage), rosiglitazone (Avandia), and pioglitazone (Actos). Other treatments with anti-oxidant effects may prove of value.

The bottom line, however, is that the single most effective treatment for obese people with NASH is to simply lose weight through diet and exercise. Unfortunately, this is no easy task in our present society, which is dominated by a sedentary lifestyle and high-calorie, high-carbohydrate, high-fat diets. With great effort, however, weight loss is achievable. Furthermore, in view of the likely role of fatty infiltration in other liver diseases, weight loss might be added on to the treatment of these other liver diseases, such as anti-viral therapy for HCV. Ultimately, NASH can probably be largely prevented and eliminated by promoting healthy eating habits and active lifestyles in children, where it all begins.

NAFLD and NASH At A Glance

• Accumulation of fat in the liver (fatty liver) is common to all stages of nonalcoholic fatty liver disease (NAFLD). The initial stage in the spectrum of NAFLD is simple fatty liver (steatosis).

• The basic cause of NAFLD is insulin resistance, which is a biochemical state that diminishes the effects of insulin. The most frequent risk factor for insulin resistance is obesity, especially abdominal obesity.

• Simple fatty liver is in itself quite harmless, disappears rapidly with weight loss, and only a minority of those affected progress to NASH, which is the next stage of NAFLD,

• Along with the accumulation of liver fat, NASH involves inflammation of the liver (hepatitis), destruction (necrosis) of liver cells, and scarring (fibrosis) of the liver. It can progress to severe liver disease, including cirrhosis, which is the last stage of NAFLD.

• The risk factors, the time-line, and the processes (mechanisms) responsible for progression through the stages of NAFLD are still unknown.

• Estimates of the number of cases of NAFLD among the obese and patients with diabetes mellitus type 2 (DM2) suggest that 90% have simple fatty liver, 20% have NASH, and 10% have cirrhosis. Among those with cirrhosis, primary liver cancer develops at a rate of approximately 1% to 2% per year.

• The presumptive diagnosis of NAFLD or NASH is made in individuals who are insulin resistant, have mildly elevated liver enzymes (transaminases) in the blood, and have signs of fatty liver on an ultrasound. These patients will have no other known cause for these enzyme elevations or for the fatty liver, particularly no significant alcohol use.

• If weight loss results in a decrease or normalization of the liver enzymes, the diagnosis of NAFLD is practically assured. Only a liver biopsy, however, can confirm the diagnosis of NAFLD and NASH and determine the severity of the disease.

• Whether or not it is vital to perform a liver biopsy in suspected NAFLD or NASH is still debated among liver specialists since no specific treatments are available. A liver biopsy can exclude other liver diseases and provide information about the outcome (prognosis) of the condition.

• A liver biopsy may also provide an incentive for the patient to adopt a healthy lifestyle (diet and exercise) with the aim of losing weight. Weight loss, if overweight, and correcting elevated cholesterol, triglycerides, and blood sugar should be beneficial in NAFLD.