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Liver and intrahepatic bile ducts-nontumor

Hepatitis - noninfectious

Nonalcoholic steatohepatitis (NASH)


Reviewers: Komal Arora, M.D. (see Reviewers page)
Revised: 5 May 2012, last major update May 2012
Copyright: (c) 2004-2012, PathologyOutlines.com, Inc.

General
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● Resembles alcoholic liver disease clinically and histologically, but by definition, alcohol is not a possible etiologic factor
● Occurs in children and adults; associated with obesity (affected 20% of markedly obese patients in an autopsy study), diabetes, drugs/toxins (including amiodarone, glucocorticoids, methotrexate, nifedipine, perhexiline maleate, synthetic estrogens, tamoxifen) or idiopathic
● Also associated with other chronic liver disease (Mod Pathol 2003;16:86)
● Due to complex metabolic derangements and necroinflammatory lesions causing hepatocellular fat accumulation, hepatocyte injury, inflammation and perisinusoidal fibrosis that may progress to cirrhosis
● May be mediated by Kupffer cells (Mod Pathol 2002;15:699)
● Often positive antinuclear antibodies in obese patients
● 15-20% progress to cirrhosis
● Presence of hepatocyte injury (ballooning degeneration or Mallory bodies) is associated with fibrosis (Hum Pathol 2004;35:196), fibrosis is associated with hepatic stellate cell activation (alpha smooth muscle actin+, Hum Pathol 2000;31:822)

Diagrams
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Conceptual pathogenesis of NASH

Treatment
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● Weight reduction; possibly bariatric surgery for morbidly obese

Micro description
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● Micro- and macrovesicular steatosis, mild lobular plasma cell and lymphocyte infiltrate with variable involvement of portal tracts, ballooning degeneration of hepatocytes with Mallory’s hyaline, intra-acinar perisinusoidal fibrosis
● Lesions usually centrilobular; glycogenated nuclei with diabetes, lipogranulomas, no neutrophils
Note: diagnosis requires both evidence of hepatocyte injury and steatosis
● Grading and staging for NASH follows methods of separate assessment for necroinflammatory lesions (grade) and fibrosis (stage) accepted in other forms of non-biliary chronic liver disease

Micro images
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Trichrome stain


Severe NASH


Primary biliary cirrhosis related


Alpha-1-antitrypsin deficiency related


Hepatitis C related

Additional references
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Hepatol Res 2005;33:68, Clin Gastroenterol Hepatol 2006;4:226

End of Liver and intrahepatic bile ducts-nontumor > Hepatitis - noninfectious > Nonalcoholic steatohepatitis (NASH)


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