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Vacuolation in hepatocyte nuclei is a marker of senescence
  1. Aloysious Aravinthan1,
  2. Suman Verma1,
  3. Nick Coleman2,
  4. Susan Davies3,
  5. Michael Allison1,
  6. Graeme Alexander1
  1. 1Division of Gastroenterology & Hepatology, University Department of Medicine, Cambridge University Hospitals, Cambridge, UK
  2. 2Hutchison/MRC Cancer Research Cell Unit, Cambridge, UK
  3. 3Department of Pathology, Cambridge University Hospitals, Cambridge, UK
  1. Correspondence to Dr Graeme Alexander, Division of Gastroenterology & Hepatology, University Department of Medicine, Box 157, Cambridge University Hospitals, Hills Road, Cambridge CB2 0QQ, UK; gja1000{at}


Hepatocyte nuclear vacuolation is considered benign and associated with non-alcohol-related fatty liver disease. Vacuolated hepatocyte nuclei were compared with non-vacuolated hepatocyte nuclei in eight patients with advanced fibrosis and a spectrum of liver disease to explore the hypothesis that such nuclei represent senescence. Age- and sex-matched liver donors served as normal tissue. In normal liver <0.01% hepatocytes showed nuclear vacuolation. In contrast, nuclear vacuolation was present in all patients with liver disease, ranging from 0.1% to 11.7% hepatocytes, irrespective of the aetiology of liver disease and independent of insulin resistance. There was a close association between nuclear vacuolation and increased nuclear area, p21 expression, γH2AX expression and the absence of Mcm-2, consistent with senescence and cell cycle arrest. Nuclear vacuolation in hepatocytes is a marker of senescence and likely to be a consequence of liver injury, unrelated to insulin resistance.

  • Vacuolated nucleus senescence
  • liver
  • liver disease

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  • Funding The study was supported by the Hepatology Endowment Fund of Cambridge University Hospitals NHS Trust.

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.