CoChat
Sign Up
Cited by 105Liver physiology and pathologyHepatitis B Virus StudiesHepatitis C virus research

Changes to hepatocyte ploidy and binuclearity profiles during human chronic viral hepatitis

Open access
Toyoda, H, Bregerie, O, Vallet, A, Nalpas, B, Pivert, G, Brechot, C, Desdouets, C·2005·Gut
DOI 10.1136/gut.2004.043893PMC PMC1774850
Open this paper in CoChat — free accountOpen PDF

Abstract

Background and aim: The importance of the hepatocyte ploidisation pattern to the control of cell proliferation and differentiation has been well established. However, there are no data that have characterised hepatocyte ploidy at various stages of chronic liver inflammation and fibrosis in vivo. Methods: We therefore investigated hepatocyte ploidy/binuclearity patterns in 57 patients with chronic hepatitis, using a recently developed methodology which allows simultaneous hepatocyte ploidy and binuclearity analyses on the same liver section. Results: The percentage of mononuclear diploid hepatocytes was significantly reduced in patients with high hepatitis activity and marked fibrosis (low activity: 75.1 (18.8)% v high activity: 61.8 (21.6)%, p = 0.0111, and low fibrosis: 77.3 (13.8)% v high fibrosis: 57.4 (23.3)%, p = 0.0002). Accordingly, the percentage of mononuclear polyploid hepatocytes increased in patients with high hepatitis activity and marked fibrosis (low activity: 11.9 (15.5)% v high activity: 22.2 (20.1)%, p = 0.0166, and low fibrosis: 9.4 (10.7)% v high fibrosis: 26.4 (21.6)%, p = 0.0001). In addition, the fraction of binuclear hepatocytes was significantly higher in patients with hepatitis B virus (HBV) than in those with hepatitis C virus (HCV) infections (HBV: 18.2 (7.6)% v HCV: 12.0 (4.8)%; p = 0.0020). Under multivariate analysis, HBV infection was an independent factor accounting for the larger binuclear hepatocyte fraction (p = 0.0294). Conclusion: Our results revealed an increase in the polyploid hepatocyte fraction which correlates with the severity of chronic hepatitis; moreover, we demonstrated that HBV and HCV related chronic hepatitis exhibited distinctive hepatocyte ploidy patterns, thus allowing the suggestion that these two viral infections may modulate liver ploidy through different mechanisms.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1136/gut.2004.043893

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Telomere deprotection and infection by HBV or HCV promote polyploidisation via unknown mechanisms.

    “Telomere deprotection162 and infection by HBV or HCV163,164 were also reported to promote polyploidisation via unknown mechanisms.”

    From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [163]

    The Results and Conclusion (page not provided) report that the polyploid hepatocyte fraction increased with the severity of chronic hepatitis and suggest that HBV and HCV may modulate liver ploidy through different mechanisms. The Discussion (page not provided) calls for investigation of those mechanisms; it does not establish that infection itself promotes polyploidisation. The telomere-deprotection clause is attached to a different citation and is not judged here. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 23

  1. Nadal C, Zajdela F. Hepatic polyploidy in the rat. IV. Experimental changes in the nucleolar volume of liver cells and their mechanisms of regulation. Exp Cell Res 1967;48:518-28.
  2. Saeter G, Schwarze E, Seglen O. Shift from polyploidizing to nonpolyploidizing growth in carcinogen-treated rat liver. J Natl Cancer Inst 1988;80:950-8.
  3. Wheatley DN. Binucleation in mammalian liver. Studies on the control of cytokinesis in vivo. Exp Cell Res 1972;74:455-65.
  4. Koike Y, Suzuki Y, Nagata A, et al. Studies on DNA content of hepatocytes in cirrhosis and hepatoma by means of microspectrophotometry and radioautography. Histochemistry 1982;75:549-62.
  5. Kudryavtsev BN, Kudryavtseva MV, Sakuta GA, et al. Human hepatocyte polyploidization kinetics in the course of life cycle. Virchows Arch B Cell Pathol Incl Mol Pathol 1993;64:387-93.
  6. Melchiorri C, Bolondi L, Chieco P, et al. Diagnostic and prognostic value of DNA ploidy and cell nuclearity in ultrasound-guided liver biopsies. Cancer 1994;74:1713-19.
  7. Saeter G, Lee CZ, Schwarze PE, et al. Changes in ploidy distributions in human liver carcinogenesis. J Natl Cancer Inst 1988;80:1480-5.
  8. Brodsky WY, Uryvaeva IV. Cell polyploidy: its relation to tissue growth and function. Int Rev Cytol 1977;50:275-332.
  9. Gupta S. Hepatic polyploidy and liver growth control. Semin Cancer Biol 2000;10:161-71.
  10. Sigal SH, Gupta S, Gebhard DF, et al. Evidence for a terminal differentiation process in the rat liver. Differentiation 1995;59:35-42.
  11. Gorla GR, Malhi H, Gupta S. Polyploidy associated with oxidative injury attenuates proliferative potential of cells. J Cell Sci 2001;114:2943-51.
  12. Schmucker DL. Hepatocyte fine structure during maturation and senescence. J Electron Microsc Tech 1990;14:106-25.
  13. Sigal SH, Rajvanshi P, Gorla GR, et al. Partial hepatectomy-induced polyploidy attenuates hepatocyte replication and activates cell aging events. Am J Physiol 1999;276:G1260-72.
  14. Diez-Fernandez C, Sanz N, Alvarez AM, et al. Influence of aminoguanidine on parameters of liver injury and regeneration induced in rats by a necrogenic dose of thioacetamide. Br J Pharmacol 1998;125:102-8.
  15. Nakatani T, Inouye M, Mirochnitchenko O. Overexpression of antioxidant enzymes in transgenic mice decreases cellular ploidy during liver regeneration. Exp Cell Res 1997;236:137-46.
  16. Schwarze PE, Pettersen EO, Shoaib MC, et al. Emergence of a population of small, diploid hepatocytes during hepatocarcinogenesis. Carcinogenesis 1984;5:1267-75.
  17. Anti M, Marra G, Rapaccini GL, et al. DNA ploidy pattern in human chronic liver diseases and hepatic nodular lesions. Flow cytometric analysis on echo- guided needle liver biopsy. Cancer 1994;73:281-8.
  18. Oriyama T, Yamanaka N, Fujimoto J, et al. Progression of hepatocellular carcinoma as reflected by nuclear DNA ploidy and cellular differentiation. J Hepatol 1998;28:142-9.
  19. Hoso M, Nakanuma Y. Cytophotometric DNA analysis of adenomatous hyperplasia in cirrhotic livers. Virchows Arch A Pathol Anat Histopathol 1991;418:401-4.
  20. Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology 1996;24:289-93.
  21. Chassoux D, Franchi J, Cao T, et al. DNA content by in situ fluorescence imaging and S-phase detection, with chromatin structure preserved. Anal Quant Cytol Histol 1999;21:489-97.
  22. Brechot C, Gozuacik D, Murakami Y, et al. Molecular bases for the development of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Semin Cancer Biol 2000;10:211-31.
  23. Hildt E, Hofschneider PH. The PreS2 activators of the hepatitis B virus: activators of tumour promoter pathways. Recent Results Cancer Res 1998;154:315-29.

Cited by

Sorted by citations

Authors
Toyoda, H., Bregerie, O., Vallet, A., Nalpas, B., Pivert, G., Brechot, C., & Desdouets, C.
Affiliations
Hôpital Necker-Enfants Malades (FR)
Corresponding author
Desdouets, C
ORCID
Venue
Gut
Publisher
BMJ
Published
2005-01-11
Volume
54
Issue
2
Pages
297-302
ISSN
  • 0017-5749 (ISSN-L)
  • 1468-3288
DOI
10.1136/gut.2004.043893
PMC
PMC1774850
OpenAlex
W2029328710
Cited by
105
References
1
Citations by year
2026: 5 · 2025: 3 · 2024: 6 · 2023: 9 · 2022: 9 · 2021: 12 · 2020: 8 · 2019: 7 · 2018: 7 · 2017: 2 · 2016: 7 · 2015: 2 · 2014: 1 · 2013: 5 · 2012: 4
FWCI
1.54
Type
journal article
Language
en
Open access
Locations
  • Gut (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
Institut National de la Recherche Agronomique
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Epidemiology › Hepatitis B Virus Studies
  • Health Sciences › Medicine › Hepatology › Hepatitis C virus research
Keywords
hepatocyte ploidy, binuclear hepatocytes, chronic viral hepatitis, hepatitis B virus, hepatitis C virus, liver fibrosis, liver inflammation, hepatocyte proliferation
MeSH terms
Adult, Cell Nucleus, Female, Humans, Liver Cirrhosis, Male, Microscopy, Fluorescence, Middle Aged, Ploidies, Severity of Illness Index, Disease Progression, Hepatitis B, Chronic, Hepatitis C, Chronic, Hepatocytes

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review