Ballooned hepatocytes in steatohepatitis: the value of keratin immunohistochemistry for diagnosis

J Hepatol. 2008 May;48(5):821-8. doi: 10.1016/j.jhep.2008.01.026. Epub 2008 Feb 22.


Background/aims: Hepatocyte "ballooning" is an often used but ill defined term in liver pathology to designate a special form of liver cell degeneration associated with cell swelling and enlargement found particularly in steatohepatitis. Alterations of the intermediate filament cytoskeleton of the hepatocyte may contribute to the pathogenesis of this microscopic change. Ballooning degeneration is considered a hallmark of steatohepatitis, but enlarged hepatocytes may also be observed in a variety of other acute and chronic liver diseases.

Methods: The intermediate filament cytoskeleton was investigated using keratin 8 and 18 immunohistochemistry in liver diseases associated with enlarged or ballooned hepatocytes.

Results: Keratin 8/18 immunostaining was drastically reduced or lost in the cytoplasm of ballooned hepatocytes in alcoholic and non-alcoholic steatohepatitis, chronic cholestatic conditions, ischemia/reperfusion injury and in ballooned hepatocytes in chronic hepatitis C cases with concurrent steatohepatitis. In contrast, substantial decrease or loss of keratin 8/18 immunostaining was not noted in cases of acute hepatitis, giant cell hepatitis, chronic hepatitis B, or autoimmune hepatitis.

Conclusions: Loss of keratin 8/18 immunostaining can serve as an objective marker of a specific type of ballooning degeneration of hepatocytes. Oxidative stress may be a common denominator in the pathogenesis of keratin filament alterations in these conditions.

MeSH terms

  • Adaptor Proteins, Signal Transducing / analysis
  • Biliary Atresia / pathology
  • Cholestasis / pathology
  • Fatty Liver / diagnosis*
  • Fatty Liver / metabolism
  • Fatty Liver / pathology*
  • Hepatocytes / pathology*
  • Humans
  • Immunohistochemistry
  • Keratins / analysis*
  • Liver Cirrhosis, Biliary / pathology
  • Oxidative Stress
  • Sequestosome-1 Protein
  • Ubiquitin / analysis


  • Adaptor Proteins, Signal Transducing
  • SQSTM1 protein, human
  • Sequestosome-1 Protein
  • Ubiquitin
  • Keratins