The nature and significance of liver cell vacuolation following hepatocellular injury--an analysis based on observations on rats rendered tolerant to hepatotoxic damage

Virchows Arch. 1996 Aug;428(6):353-65. doi: 10.1007/BF00202202.


Swelling with nonlipid cytoplasmic vacuolation of diffusely distributed hepatocytes is seen consistently after mild acute and subacute liver injury. Several lines of evidence point to the possibility that this change may reflect a cellular adaptation beneficial to the host, rather than a degenerative change. The nature and significance of this morphological manifestation were tested in batches of albino rats given small doses of a variety of hepatotoxins, some of which were subsequently challenged with a large highly necrogenic dose of carbon tetrachloride (CCl4). Morphological and biochemical investigations showed that cytoplasmic vacuolation of liver cells following low doses of toxins was due to excess accumulation of glycogen, predominantly of the monoparticulate form. These cells lacked features of degeneration or regeneration and were much less susceptible to injury by the large dose CCl4, as assessed by structural and serum enzyme analyses. This tolerance to toxic damage seemed to be associated with excess accumulation of intracellular glycogen. We conclude from these and other observations on animal and human livers that many of the vacuolated hepatocytes seen in liver injury are cells adaptively altered to resist further insult rather than cells undergoing hydropic degeneration, as is commonly believed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • Aflatoxin B1
  • Alanine Transaminase / analysis
  • Animals
  • Aspartate Aminotransferases / analysis
  • Carbon Tetrachloride
  • Carcinogens
  • Chemical and Drug Induced Liver Injury
  • Cytoplasm / ultrastructure
  • Drug Tolerance / physiology
  • Fasting / physiology
  • Formic Acid Esters
  • Glycogen / chemistry
  • Glycogen / ultrastructure
  • Liver / pathology
  • Liver / physiopathology
  • Liver Diseases / pathology*
  • Liver Diseases / physiopathology
  • Male
  • Microscopy, Electron
  • Rats
  • Rats, Wistar
  • Vacuoles / pathology*


  • Carcinogens
  • Formic Acid Esters
  • Glycogen
  • Aflatoxin B1
  • allyl formate
  • Carbon Tetrachloride
  • Aspartate Aminotransferases
  • Alanine Transaminase