Hepatocyte senescence in end-stage chronic liver disease: A study of cyclin-dependent kinase inhibitor p21 in liver biopsies as a marker for progression to hepatocellular carcinoma

Elizabeth M. Brunt, Sarah N. Walsh, Paul H. Hayashi, Jennifer Labundy, Adrian M. Di Bisceglie

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Background: Histologic markers to predict hepatocellular carcinoma (HCC) include small cell change and dysplastic nodules. Hepatocyte senescence is noted in chronic liver disease and may or may not be important in progression to HCC. Aim: The study was undertaken to compare standard histologic features of chronic liver disease as well as markers of senescence and proliferation in two groups of biopsies from patients followed for at least a year. Methods: Standard histologic evaluation of necroinflammatory activity, fibrosis, steatosis, and iron, internationally accepted criteria of dysplasia, and immunohistochemical markers for proliferation and hepatocyte senescence were compared in 47 liver biopsies from noncholestatic chronic liver disease patients who subsequently either underwent transplant (the Control group, n=19) or had biopsy-proven (HCC group, n=28) over a similar time period of 34.9 months (mean) and 42.5 months (mean) respectively. Results: Both groups were predominantly men; the MELD score was higher, and mean age was less in the Control group (46.9 vs 53.8 years, P=0.01). Small cell change was not significantly different in the biopsies between the two groups; neither were grade, stage (Ishak scores), nor presence or location of iron. Steatosis was more common in the group that subsequently developed HCC (P=0.04). The MIB-1 proliferation index was greater in the biopsies from the Control group. The senescence marker p21, and the ratio of p21:MIB-1 were not statistically different between the two groups. However, a Spearman's rank correlation showed a linear correlation of p21/MIB-1 with a greater amount of dyplasia in the explant livers of Controls. Conclusions: These findings suggested the Control groups' livers maintained effective removal of cells from the cell cycle by overexpression of p21 and, while not 'protected' from significant involvement by dysplasia, may have been precluded from development of HCC.

Original languageEnglish
Pages (from-to)662-671
Number of pages10
JournalLiver International
Volume27
Issue number5
DOIs
StatePublished - Jun 2007

Keywords

  • Chronic liver disease
  • Hepatocellular carcinoma
  • Senescense

Fingerprint

Dive into the research topics of 'Hepatocyte senescence in end-stage chronic liver disease: A study of cyclin-dependent kinase inhibitor p21 in liver biopsies as a marker for progression to hepatocellular carcinoma'. Together they form a unique fingerprint.

Cite this