Kupffer cell-dependent hepatitis occurs during influenza infection

Am J Pathol. 2006 Apr;168(4):1169-78; quiz 1404-5. doi: 10.2353/ajpath.2006.050875.


Respiratory infections, including influenza in humans, are often accompanied by a hepatitis that is usually mild and self-limiting. The mechanism of this kind of liver damage is not well understood. In the present study, we show that influenza-associated hepatitis occurs due to the formation of inflammatory foci that include apoptotic hepatocytes, antigen-specific CD8(+) T cells, and Kupffer cells. Serum aminotransaminase levels were elevated, and both the histological and serum enzyme markers of hepatitis were increased in secondary influenza infection, consistent with a primary role for antigen-specific T cells in the pathogenesis. No virus could be detected in the liver, making this a pure example of "collateral damage" of the liver. Notably, removal of the Kupffer cells prevented the hepatitis. Such hepatic collateral damage may be a general consequence of expanding CD8(+) T-cell populations during many extrahepatic viral infections, yielding important implications for liver pathobiology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alanine Transaminase / blood
  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Hepatitis / etiology*
  • Hepatitis / pathology
  • Hepatitis / virology
  • Hepatocytes / immunology
  • Hepatocytes / pathology
  • Hepatocytes / virology
  • Humans
  • Influenza A Virus, H1N1 Subtype
  • Influenza, Human / complications*
  • Influenza, Human / immunology
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / pathology
  • Kupffer Cells / immunology*
  • Kupffer Cells / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Middle Aged


  • Alanine Transaminase