Skip to main content
SpringerLink
Log in

New Histological Staging and Grading System for Primary Biliary Cirrhosis

  • Chapter
  • First Online:
Autoimmune Liver Diseases

  • 909 Accesses

Abstract

Scheuer’s and Ludwig’s are the two histological staging systems for primary biliary cirrhosis (PBC) that have been used worldwide since the 1960s. In these classical staging systems, PBC livers were classified into four stages on the basis of a single characteristic histological feature of PBC such as chronic nonsuppurative destructive cholangitis and bile ductular proliferation. It is well known that these histological features are heterogeneously distributed in the liver; therefore, sampling errors are often unavoidable in these classical staging systems. In addition, there have been no categories on the grading system for necroinflammation characterizing PBC. We recently proposed a new histological staging and grading system in which we consider the degree of fibrosis, bile duct loss, and chronic cholestasis in combination for staging, in order to reduce sampling errors. Scores for the degree of both chronic cholangitis activity (CA) and hepatitic activity (HA) for grading disease activity were also proposed. Our recent study demonstrated that this new system provides more information, which is consistent with clinical laboratory data and a better reflection of the prognosis of PBC patients. Herein, the new histological system for staging and grading of PBC is reviewed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Nakanuma Y, Zen Y, Portmann BC (2011) Diseases of the bile ducts. In: Burt AD, Portmann BC, Ferrell LD (eds) MacSween’s pathology of the liver, 6th edn. Churchill Livingstone, London, pp 491–562

    Google Scholar 

  2. Kaplan MM, Gershwin ME (2005) Primary biliary cirrhosis. New Eng J Med 353(12):1261–1273. doi:10.1056/NEJMra043898

    Article  CAS  PubMed  Google Scholar 

  3. Poupon R (2010) Primary biliary cirrhosis: a 2010 update. J Hepatol 52:745–758

    Article  PubMed  Google Scholar 

  4. Rubin E, Schaffner F, Popper H (1965) Primary biliary cirrhosis. Chronic non-suppurative destructive cholangitis. Am J Pathol 46:387–407

    CAS  PubMed Central  PubMed  Google Scholar 

  5. Ludwig J, Czaja AJ, Dickson ER, LaRusso NF, Wiesner RH (1984) Manifestations of nonsuppurative cholangitis in chronic hepatobiliary diseases: morphologic spectrum, clinical correlations and terminology. Liver 4(2):105–116

    Article  CAS  PubMed  Google Scholar 

  6. Zen Y, Harada K, Sasaki M, Tsuneyama K, Matsui K, Haratake J, Sakisaka S, Maeyama S, Yamamoto K, Nakano M, Shimamatsu K, Kage M, Kurose N, Uchiyama A, Kaizaki Y, Toda G, Nakanuma Y (2005) Are bile duct lesions of primary biliary cirrhosis distinguishable from those of autoimmune hepatitis and chronic viral hepatitis? Interobserver histological agreement on trimmed bile ducts. J Gastroenterol 40(2):164–170. doi:10.1007/s00535-004-1514-7

    Article  PubMed  Google Scholar 

  7. Lee H, Stapp RT, Ormsby AH, Shah VV (2010) The usefulness of IgG and IgM immunostaining of periportal inflammatory cells (plasma cells and lymphocytes) for the distinction of autoimmune hepatitis and primary biliary cirrhosis and their staining pattern in autoimmune hepatitis-primary biliary cirrhosis overlap syndrome. Am J Clin Pathol 133(3):430–437. doi:10.1309/AJCPE93GZSHUNTAI

    Article  PubMed  Google Scholar 

  8. Nakanuma Y, Hirata K (1993) Unusual hepatocellular lesions in primary biliary cirrhosis resembling but unrelated to hepatocellular neoplasms. Virchows Arch A Pathol Anat Histopathol 422(1):17–23

    Article  CAS  PubMed  Google Scholar 

  9. Nakanuma Y, Ohta G (1987) Nodular hyperplasia of the liver in primary biliary cirrhosis of early histological stages. Am J Gastroenterol 82(1):8–10

    CAS  PubMed  Google Scholar 

  10. Terasaki S, Nakanuma Y, Yamazaki M, Unoura M (1993) Eosinophilic infiltration of the liver in primary biliary cirrhosis: a morphological study. Hepatology 17(2):206–212

    Article  CAS  PubMed  Google Scholar 

  11. Scheuer P (1967) Primary biliary cirrhosis. Proc R Soc Med 60(12):1257–1260

    CAS  PubMed Central  PubMed  Google Scholar 

  12. Ludwig J, Dickson ER, McDonald GS (1978) Staging of chronic nonsuppurative destructive cholangitis (syndrome of primary biliary cirrhosis). Virchows Arch A Pathol Anat Histol 379(2):103–112

    Article  CAS  PubMed  Google Scholar 

  13. Corpechot C, Carrat F, Poupon R, Poupon R-E (2002) Primary biliary cirrhosis: incidence and predictive factors of cirrhosis development in ursodiol-treated patients. Gastroenterology 122(3):652–658. doi:10.1053/gast.2002.31880

    Article  CAS  PubMed  Google Scholar 

  14. Corpechot C, Abenavoli L, Rabahi N, Chretien Y, Andreani T, Johanet C, Chazouilleres O, Poupon R (2008) Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis. Hepatology 48(3):871–877. doi:10.1002/hep.22428

    Article  CAS  PubMed  Google Scholar 

  15. Corpechot C, Chazouilleres O, Poupon R (2011) Early primary biliary cirrhosis: biochemical response to treatment and prediction of long-term outcome. J Hepatol 55(6):1361–1367. doi:10.1016/j.jhep.2011.02.031

    Article  CAS  PubMed  Google Scholar 

  16. Kumagi T, Guindi M, Fischer SE, Arenovich T, Abdalian R, Coltescu C, Heathcote EJ, Hirschfield GM (2010) Baseline ductopenia and treatment response predict long-term histological progression in primary biliary cirrhosis. Am J Gastroenterol 105(10):2186–2194. doi:10.1038/ajg.2010.216

    Article  CAS  PubMed  Google Scholar 

  17. Roll J, Boyer JL, Barry D, Klatskin G (1983) The prognostic importance of clinical and histologic features in asymptomatic and symptomatic primary biliary cirrhosis. New England J Med 308(1):1–7. doi:10.1056/nejm198301063080101

  18. Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, Denk H, Desmet V, Korb G, MacSween RN et al (1995) Histological grading and staging of chronic hepatitis. J Hepatol 22(6):696–699

    Article  CAS  PubMed  Google Scholar 

  19. Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR (1999) Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 94(9):2467–2474. doi:10.1111/j.1572-0241.1999.01377.x

    Article  CAS  PubMed  Google Scholar 

  20. Hiramatsu K, Aoyama H, Zen Y, Aishima S, Kitagawa S, Nakanuma Y (2006) Proposal of a new staging and grading system of the liver for primary biliary cirrhosis. Histopathology 49(5):466–478. doi:10.1111/j.1365-2559.2006.02537.x

    Article  CAS  PubMed  Google Scholar 

  21. Dickson ER, Grambsch PM, Fleming TR, Fisher LD, Langworthy A (1989) Prognosis in primary biliary cirrhosis: model for decision making. Hepatology 10(1):1–7

    Article  CAS  PubMed  Google Scholar 

  22. Murtaugh PA, Dickson ER, Van Dam GM, Malinchoc M, Grambsch PM, Langworthy AL, Gips CH (1994) Primary biliary cirrhosis: prediction of short-term survival based on repeated patient visits. Hepatology 20(1 Pt 1):126–134

    Article  CAS  PubMed  Google Scholar 

  23. Nakanuma Y, Zen Y, Harada K, Sasaki M, Nonomura A, Uehara T, Sano K, Kondo F, Fukusato T, Tsuneyama K, Ito M, Wakasa K, Nomoto M, Minato H, Haga H, Kage M, Yano H, Haratake J, Aishima S, Masuda T, Aoyama H, Miyakawa-Hayashino A, Matsumoto T, Sanefuji H, Ojima H, Chen TC, Yu E, Kim JH, Park YN, Tsui W (2010) Application of a new histological staging and grading system for primary biliary cirrhosis to liver biopsy specimens: interobserver agreement. Pathol Int 60(3):167–174. doi:10.1111/j.1440-1827.2009.02500.x

    Article  PubMed  Google Scholar 

  24. Nakanuma Y, Karino T, Ohta G (1979) Orcein positive granules in the hepatocytes in chronic intrahepatic cholestasis. Morphological, histochemical and electron X-ray microanalytical examination. Virchows Arch A Pathol Anat Histol 382(1):21–30

    Article  CAS  PubMed  Google Scholar 

  25. Jain S, Scheuer PJ, Archer B, Newman SP, Sherlock S (1978) Histological demonstration of copper and copper-associated protein in chronic liver diseases. J Clin Pathol 31(8):784–790

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Chazouilleres O, Wendum D, Serfaty L, Montembault S, Rosmorduc O, Poupon R (1998) Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome: clinical features and response to therapy. Hepatology 28(2):296–301. doi:10.1002/hep.510280203

    Article  CAS  PubMed  Google Scholar 

  27. Harada K, Hsu M, Ikeda H, Zeniya M, Nakanuma Y (2013) Application and validation of a new histologic staging and grading system for primary biliary cirrhosis. J Clin Gastroenterol 47(2):174–181. doi:10.1097/MCG.0b013e31827234e4

    Article  PubMed  Google Scholar 

  28. Kakuda Y, Harada K, Sawada-Kitamura S, Ikeda H, Sato Y, Sasaki M, Okafuji H, Mizukoshi E, Terasaki S, Ohta H, Kasashima S, Kawashima A, Kaizaki Y, Kaneko S, Nakanuma Y (2013) Evaluation of a new histologic staging and grading system for primary biliary cirrhosis in comparison with classical systems. Hum Pathol 44(6):1107–1117. doi:10.1016/j.humpath.2012.09.017

    Article  PubMed  Google Scholar 

  29. Nakanuma Y, Hoso M, Mizuno Y, Unoura M (1988) Pathologic study of primary biliary cirrhosis of early histologic stages presenting cholestatic jaundice. Liver 8(6):319–324

    Google Scholar 

  30. Vleggaar FP, van Buuren HR, Zondervan PE, ten Kate FJ, Hop WC (2001) Jaundice in non-cirrhotic primary biliary cirrhosis: the premature ductopenic variant. Gut 49(2):276–281

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Abe M, Onji M (2008) Natural history of primary biliary cirrhosis. Hepatol Res 38(7):639–645. doi:10.1111/j.1872-034X.2008.00351.x

    Article  PubMed  Google Scholar 

  32. Colina F, Pinedo F, Solis JA, Moreno D, Nevado M (1992) Nodular regenerative hyperplasia of the liver in early histological stages of primary biliary cirrhosis. Gastroenterology 102(4 Pt 1):1319–1324

    CAS  PubMed  Google Scholar 

  33. Working Subgroup for Clinical Practice Guidelines for Primary Biliary C (2014) Guidelines for the management of primary biliary cirrhosis: the Intractable Hepatobiliary Disease Study Group supported by the Ministry of Health, Labour and Welfare of Japan. Hepatol Res 44(Suppl S1):71–90. doi:10.1111/hepr.12270

  34. Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ, American Association for Study of Liver D (2009) Primary biliary cirrhosis. Hepatology 50(1):291–308. doi:10.1002/hep.22906

    Article  PubMed  Google Scholar 

  35. European Association for the Study of the L (2009) EASL clinical practice guidelines: management of cholestatic liver diseases. J Hepatol 51(2):237–267. doi:10.1016/j.jhep.2009.04.009

    Article  Google Scholar 

  36. Silveira MG, Brunt EM, Heathcote J, Gores GJ, Lindor KD, Mayo MJ (2010) American Association for the Study of Liver Diseases endpoints conference: design and endpoints for clinical trials in primary biliary cirrhosis. Hepatology 52(1):349–359. doi:10.1002/hep.23637

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Human Pathology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa, 920-8641, Japan

    Yuko Kakuda, Kenichi Harada & Yasuni Nakanuma M.D., Ph.D.

  2. Department of Pathology, Shizuoka Cancer Center, Shizuoka, Japan

    Yuko Kakuda & Yasuni Nakanuma M.D., Ph.D.

Authors
  1. Yuko Kakuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kenichi Harada
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yasuni Nakanuma M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yasuni Nakanuma M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. Dept of Gastroenterology & Rheumatology, Fukushima Medical University of Medicine, Fukushima, Japan

    Hiromasa Ohira

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Japan

About this chapter

Cite this chapter

Kakuda, Y., Harada, K., Nakanuma, Y. (2014). New Histological Staging and Grading System for Primary Biliary Cirrhosis. In: Ohira, H. (eds) Autoimmune Liver Diseases. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54789-1_16

Download citation

  • DOI: https://doi.org/10.1007/978-4-431-54789-1_16

  • Published:

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-54788-4

  • Online ISBN: 978-4-431-54789-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation