Vacuolation in hepatocyte nuclei is a marker of senescence
- Aloysious Aravinthan1,
- Suman Verma1,
- Nick Coleman2,
- Susan Davies3,
- Michael Allison1,
- Graeme Alexander1
- 1Division of Gastroenterology & Hepatology, University Department of Medicine, Cambridge University Hospitals, Cambridge, UK
- 2Hutchison/MRC Cancer Research Cell Unit, Cambridge, UK
- 3Department of Pathology, Cambridge University Hospitals, Cambridge, UK
- Correspondence to Dr Graeme Alexander, Division of Gastroenterology & Hepatology, University Department of Medicine, Box 157, Cambridge University Hospitals, Hills Road, Cambridge CB2 0QQ, UK;
Contributors AA and GA developed the concept and manuscript. SV and NC assisted in technical development. SD conducted the pathology review. MA carried out the clinical review.
- Accepted 15 February 2012
- Published Online First 23 March 2012
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.
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.