Nonalcoholic Fatty Liver Disease

DEFINITION

• Nonalcoholic fatty liver disease (NAFLD): fatty infiltration (steatosis) of the liver, exceeding 5% of liver weight. In biopsy specimens, >5-10% macrosteatotic hepatocytes.
  • By definition, requires exclusion of alcohol as a potential cause. Acceptable levels of alcohol consumption are controversial but in general < 20 grams/day (2 drinks) in men and < 10 grams/day (1 drink) in women are considered safe, and below the cutoff associated with increased risk of cirrhosis (30 grams/day in men and 20 grams/day in women).
• Primary NAFLD: common term for typical NAFLD associated with central obesity and/or type 2 diabetes (T2DM) or insulin resistance (IR), without another specific etiology.
• Secondary NAFLD: used to defined as NAFLD in the absence of insulin resistance and associated with other causes such as: polycystic ovary syndrome, hypothyroidism, hypogonadism, hypopituitarism, medication use (glucocorticoids, tamoxifen, amiodarone, HAART, diltiazem), disorders of lipid metabolism (abetalipoproteinemia, lipodystrophy, Weber-Christian syndrome, Andersen’s disease), total parenteral nutrition and jejunoileal bypass surgery. Many cases of "secondary" NAFLD likely represent an exacerbation of often unrecognized "primary" NAFLD.
• Nonalcoholic steatohepatitis (NASH): the more severe form of NAFLD characterized by inflammation, hepatocyte injury (ballooned hepatocytes), with or without fibrosis. It can progress to cirrhosis and possibly liver cancer.
• NASH cirrhosis: the presence of cirrhosis with current or previous evidence of steatosis or NASH.
• Cryptogenic cirrhosis: a term used to define the presence of cirrhosis with no obvious etiology, however, frequently there is a history of diabetes and obesity.