DEFINITIONS

NAFLD is the leading cause of chronic liver disease

Non-alcoholic fatty liver disease (NAFLD) is increasingly common worldwide and has become the principal cause of chronic liver disease. NAFLD can be subdivided into non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). To diagnose NAFLD, there must be (a) evidence of hepatic steatosis, either by imaging or histology, and (b) lack of secondary causes of hepatic fat accumulation such as significant alcohol consumption, long-term use of a steatogenic medication, or monogenic hereditary disorders.

NASH covers a wide spectrum of disease severity

Whereas NAFL (or steatosis) is defined as hepatic fat content of ≥5% of liver weight or ≥5% fat-loaded hepatocytes with no evidence of hepatocellular injury (ballooning) or fibrosis, NASH is characterized by hepatic steatosis ≥5%, lobular inflammation and ballooned hepatocytes (as a marker of hepatocyte injury), with or without the presence of hepatic fibrosis. NASH thus covers a wide spectrum of disease severity in individuals without significant alcohol consumption (less than 20 g/d for women and 30 g/d for men), and without other causes of secondary steatosis. NASH can progress to cirrhosis, liver failure and, more rarely, hepatocellular carcinoma (HCC).

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NAFLD-table
definition-table

TABLE 1. Common Causes of Secondary Hepatosteatosis

Macrovesicular steatosis
   o Excessive alcohol consumption
   o Hepatitis C (genotype 3)
   o Lipodystrophy
   o Starvation
   o Parenteral nutrition
   o Abetalipoproteinemia
   o Medications (e.g., mipomersen, lomitapide, amiodarone, methotrexate, tamoxifen, corticosteroids)
Microvesicular steatosis
   o Reye’s syndrome
   o Medications (valproate, antiretroviral medicines)
   o Acute fatty liver of pregnancy
   o HELLP syndrome
   o Inborn errors of metabolism

(e.g., lecithin-cholesterol acyltransferase deficiency, cholesterol ester storage disease, Wolman’s disease)
Adapted from Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67:328-57

References

  1. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. 2018;67:328-57
  2. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64:1388-402
  3. Stefan N, Häring HU, Cusi K. Non-alcoholic fatty liver disease: causes, diagnosis, cardiometabolic consequences, and treatment strategies. Lancet Diabetes Endocrinol. 2019;7(4):313-324.
  4. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease – Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64:73-84
  5. Younossi Z, Tacke F, Arrese M, et al. Global perspectives on non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. 2019 Jun;69(6):2672-2682
  1. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. 2018;67:328-57
  2. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64:1388-402
  3. Stefan N, Häring HU, Cusi K. Non-alcoholic fatty liver disease: causes, diagnosis, cardiometabolic consequences, and treatment strategies. Lancet Diabetes Endocrinol. 2019;7(4):313-324.
  4. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease – Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64:73-84
  5. Younossi Z, Tacke F, Arrese M, et al. Global perspectives on non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. 2019 Jun;69(6):2672-2682
  1. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. 2018;67:328-57
  2. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64:1388-402
  3. Stefan N, Häring HU, Cusi K. Non-alcoholic fatty liver disease: causes, diagnosis, cardiometabolic consequences, and treatment strategies. Lancet Diabetes Endocrinol. 2019;7(4):313-324.
  4. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease – Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64:73-84
  5. Younossi Z, Tacke F, Arrese M, et al. Global perspectives on non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. 2019 Jun;69(6):2672-2682