Fatty Liver:
Nonalcoholic Fatty Liver Disease (NAFLD)
and
Nonalcoholic Steatohepatitis (NASH)

Medical Author: Michel Mendler, M.D.
Medical Editor: Leslie J. Schoenfield, M.D., Ph.D.

• 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?
  • Patient Discussions: Fatty Liver - How Was Diagnosis Established
  • Find a local Gastroenterologist in your town
• 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

What are Fatty Liver, NAFLD, and NASH?

Nonalcoholic fatty liver disease (NAFLD) refers to a wide spectrum of liver disease ranging from simple fatty liver (steatosis), to nonalcoholic steatohepatitis (NASH), to cirrhosis (irreversible, advanced scarring of the liver). All of the stages of NAFLD have in common the accumulation of fat (fatty infiltration) in the liver cells (hepatocytes). In NASH, the fat accumulation is associated with varying degrees of inflammation (hepatitis) and scarring (fibrosis) of the liver.

The term nonalcoholic is used because NAFLD and NASH occur in individuals who do not consume excessive amounts of alcohol. Yet, in many respects, the histological picture of NAFLD (when we look at a biopsy piece of liver under the microscope) is similar to what can be seen in liver disease that is due to excessive intake of alcohol. As we shall see, however, the clinical circumstances in NAFLD and NASH are very different from those in alcoholic liver disease (ALD).

What is the NAFLD spectrum?

The NAFLD spectrum is thought to begin with and progress from its simplest stage, called simple fatty liver (steatosis). That is, fatty liver is the initial abnormality in the spectrum of NAFLD. Simple fatty liver involves just the accumulation of fat in the liver cells with no inflammation or scarring. The fat is actually composed of a particular type of fat (triglyceride) that accumulates in tiny sacs within the liver cells. This accumulation of fat in liver cells is not the same as the fat cells (adipocytes) that constitute our body fat. Fatty liver is a harmless (benign) condition, which means that it, by itself, does not cause any significant liver damage.

The next stage and degree of severity in the NAFLD spectrum is NASH. Fortunately, only a fraction of patients with simple fatty liver will develop NASH. As mentioned, NASH involves the accumulation of fat in the liver cells as well as inflammation of the liver. The inflammatory cells can destroy the liver cells (hepatocellular necrosis). In the terms "steatohepatitis" and "steatonecrosis", steato refers to fatty infiltration, hepatitis refers to inflammation in the liver, and necrosis refers to destroyed liver cells. Strong evidence suggests that NASH, in contrast to simple fatty liver, is not a harmless condition. This means that NASH can ultimately lead to scarring of the liver (fibrosis) and then irreversible, advanced scarring (cirrhosis). Cirrhosis that is caused by NASH is the last and most severe stage in the NAFLD spectrum.

Much is not yet known about NASH and NAFLD. For example, as discussed below, the progression from each of the different stages of NAFLD is not well understood. Moreover, even liver specialists still do not agree on the exact microscopic definition of NASH. Nevertheless, individuals who develop any of the three stages of NAFLD (fatty liver, NASH, or cirrhosis) share common risk factors. Accordingly, fatty liver and NASH are described in this article as part of the spectrum of NAFLD. Remember, NAFLD refers to the entire spectrum beginning with fatty liver, progressing through NASH, and ending with cirrhosis. NASH is that stage of the spectrum that involves fat accumulation (steatosis), inflammation (hepatitis), and scarring (fibrosis) in the liver.

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