Human Pathology
Volume 40, Issue 12 , Pages 1774-1782 , December 2009

Large cell change of hepatocytes in chronic viral hepatitis represents a senescent-related lesion

  • Hiroko Ikeda

      Affiliations

    • Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan
    • Molecular Cellular Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan
  • ,
  • Motoko Sasaki

      Affiliations

    • Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan
  • ,
  • Yasunori Sato

      Affiliations

    • Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan
  • ,
  • Kenichi Harada

      Affiliations

    • Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan
  • ,
  • Yoh Zen

      Affiliations

    • Section of Diagnostic Pathology, Kanazawa University Hospital, Kanazawa 920-8620, Japan
  • ,
  • Takeshi Mitsui

      Affiliations

    • Department of Surgery, Fukui Saiseikai Hospital, Fukui 918-8503, Japan
  • ,
  • Yasuni Nakanuma

      Affiliations

    • Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan
    • Corresponding Author InformationCorresponding author.

Received 4 February 2009 ,Revised 3 June 2009 ,Accepted 11 June 2009.

References 

  1. Anthony PP, Vogel CL, Barker LE. Liver cell dysplasia: a premalignant condition. L Clin Pathol. 1973;26:217–223
  2. Park YN, Roncalli M. Large liver cell dysplasia: a controversial entity. J Hepatol. 2006;45:734–743
  3. Nakanuma Y, Hirata K, Terasaki S, et al. Analytical histopathological diagnosis of small hepatocellular nodules in chronic liver disease. Histol Histopathol. 1998;13:1077–1087
  4. Natarajan S, Theise ND, Thung SN, et al. Large-cell change of hepatocytes in cirrhosis may represent a reaction to prolonged cholestasis. Am J Surg Pathol. 1997;21:312–318
  5. Lee RG, Tsamandas AC, Demetris AJ. Large cell change (liver cell dysplasia) and hepatocellular carcinoma in cirrhosis: matched case-control study, pathological analysis, and pathogenetic hypothesis. Hepatology. 1997;26:1415–1422
  6. Chung YM, Lee SB, Kim HJ, et al. Replicative senescence induced by Romo1-derived reactive oxygen species. J Biol Chem. 2008;283:33763–33771
  7. Bartkova J, Rezaei N, Liontos M, et al. Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature. 2006;444:633–637
  8. Braig M, Lee S, Loddenkemper C, et al. Oncogene-induced senescence as an initial barrier in lymphoma development. Nature. 2005;436:660–665
  9. Braig M, Schmitt CA. Oncogene-induced senescence: putting the brakes on tumor development. Cancer Res. 2006;66:2881–2884
  10. Sasaki M, Ikeda H, Haga H, et al. Frequent cellular senescence in small bile ducts in primary biliary cirrhosis: a possible role in bile duct loss. J Pathol. 2005;205:451–459
  11. Narita M, Narita M, Krizhanovsky V, et al. A novel role for high-mobility group a proteins in cellular senescence and heterochromatin formation. Cell. 2006;126:503–514
  12. Lucibello FC, Sewing A, Brüsselbach S, et al. Deregulation of cyclins D1 and E and suppression of cdk2 and cdk4 in senescent human fibroblasts. J Cell Sci. 1993;105:123–133
  13. Fukami-Kobayashi J, Mitsui Y. Cyclin D1 inhibits cell proliferation through binding to PCNA and cdk2. Exp Cell Res. 1999;246:338–347
  14. Quereda V, Martinalbo J, Dubus P, et al. Genetic cooperation between p21(Cip1) and INK4 inhibitors in cellular senescence and tumor suppression. Oncogene. 2007;26:7665–7674
  15. Batts KP, Ludwig J. Chronic hepatitis. An update on terminology and reporting. Am J Surg Pathol. 1995;19:1409–1417
  16. International Working Party . Terminology of nodular hepatocellular lesions. Hepatology. 1995;22:983–993
  17. Harada K, Sato Y, Itatsu K, et al. Innate immune response to double-stranded RNA in biliary epithelial cells is associated with the pathogenesis of biliary atresia. Hepatology. 2007;46:1146–1154
  18. Funayama R, Ishikawa F. Cellular senescence and chromatin structure. Chromosoma. 2007;116:431–440
  19. Sasaki M, Ikeda H, Sato Y, et al. Decreased expression of Bmi1 is closely associated with cellular senescence in small bile ducts in primary biliary cirrhosis. Am J Pathol. 2006;169:831–845
  20. Paradis V, Youssef N, Dargère D, et al. Replicative senescence in normal liver, chronic hepatitis C, and hepatocellular carcinomas. Hum Pathol. 2001;32:327–332
  21. Brunt EM, Walsh SN, Hayashi PH, et al. 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. Liver Int. 2007;27:662–671
  22. Tanaka H, Fujita N, Sugimoto R, et al. Hepatic oxidative DNA damage is associated with increased risk for hepatocellular carcinoma in chronic hepatitis C. Br J Cancer. 2008;98:580–586
  23. Sekoguchi S, Nakajima T, Moriguchi M, et al. Role of cell-cycle turnover and oxidative stress in telomere shortening and cellular senescence in patients with chronic hepatitis C. J Gastroenterol Hepatol. 2007;22:182–190
  24. Sherr CJ. Cancer cell cycles. Science. 1996;274:1672–1677
  25. Marshall A, Rushbrook S, Davies SE, et al. Relation between hepatocyte G1 arrest, impaired hepatic regeneration, and fibrosis in chronic hepatitis C virus infection. Gastroenterology. 2005;128:33–42
  26. Koo JS, Seong JK, Park C, et al. Large liver cell dysplasia in hepatitis B virus X transgenic mouse liver and human chronic hepatitis B virus-infected liver. Intervirology. 2005;48:16–22
  27. Gadbois DM, Peterson S, Bradbury EM, Lehnert BE. CDK4/cyclin D1/PCNA complexes during staurosporine-induced G1 arrest and G0 arrest of human fibroblasts. Exp Cell Res. 1995;220:220–225
  28. Koo JS, Kim H, Park BK, et al. Predictive value of liver cell dysplasia for development of hepatocellular carcinoma in patients with chronic hepatitis B. J Clin Gastroenterol. 2008;42:738–743
  29. Ganne-Carrie N, Chastang C, Chapel F, et al. Predictive score for the development of hepatocellular carcinoma and additional value of liver large cell dysplasia in western patients with cirrhosis. Hepatology. 1996;23:1112–1118
  30. Collado M, Gil J, Efeyan A, et al. Tumour biology: senescence in premalignant tumours. Nature. 2005;426:194–198
  31. Michaloglou C, Vredeveld LC, Soengas MS, et al. BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature. 2005;720–724

PII: S0046-8177(09)00224-X

doi: 10.1016/j.humpath.2009.06.009

Human Pathology
Volume 40, Issue 12 , Pages 1774-1782 , December 2009