Cited by 5Liver physiology and pathologyOrgan Transplantation Techniques and OutcomesTissue Engineering and Regenerative Medicine

Biochemical and morphological responses to post-hepatectomy liver failure in rats

Open access
Lund, Andrea, Andersen, Kasper Jarlhelt, Meier, Michelle, Pedersen, Marie Ingemann, Knudsen, Anders Riegels, Kirkegård, Jakob, Mortensen, Frank Viborg, Nyengaard, Jens Randel·2023·Scientific Reports

Abstract

The upper limit for partial hepatectomy (PH) in rats is 90%, which is associated with an increased risk of post-hepatectomy liver failure (PHLF), correlating with high mortality. Sixty-eight rats were randomized to 90% PH, sham operation, or no surgery. Further block randomization was performed to determine the time of euthanasia, whether 12, 24, or 48 h after surgery. A general distress score (GDS) was calculated to distinguish between rats with reversible (GDS < 10) and irreversible PHLF (GDS ≥ 10). At euthanasia, the liver remnant and blood were collected. Liver-specific biochemistry and regeneration ratio were measured. Hepatocyte proliferation and volume were estimated using stereological methods. All rats subjected to 90% experienced biochemical PHLF. The biochemical and morphological liver responses did not differ between the groups until 48 h after surgery. At 48 h, liver regeneration and function were significantly improved in survivors. The peak mean regeneration ratio was 15% for rats with irreversible PHLF compared to 26% for rats with reversible PHLF. The 90% PH rat model was associated with PHLF and high mortality. Irreversible PHLF was characterized by impaired liver regeneration capacity and an insufficient ability to metabolize ammonia.

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 · 10.1038/s41598-023-40736-y

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?

  • In experimental models, recovery of liver function has been characterized using stereological and immunohistochemical methods, including assessment of hepatocyte proliferation via Ki-67 staining and β-catenin signaling.

    “In experimental models, the recovery of liver function has been further characterized using stereological and immunohistochemical methods, including assessment of hepatocyte proliferation via Ki-67 staining and β-catenin signaling[92].”

    From Liver regeneration after partial hepatectomy: Triggers and mechanisms (2025) · cites this paper as [92]

    The Materials and methods section (Stereology; page unavailable) describes immunohistochemical staining and stereological counts of Ki-67-positive hepatocytes in rats after hepatectomy. It identifies β-catenin staining as a hepatocyte cell-surface marker for volume measurements, not an assessment of β-catenin signaling. The signaling part of the claim is therefore unsupported. (LLM, conf=0.90)

    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: 29

  1. [1]Dasgupta, P. et al. Global trends in incidence rates of primary adult liver cancers: A systematic review and meta-analysis. Front Oncol. 10, 171 (2020). 32185125 PMC7058661 · DOI
  2. [2]Lintoiu-Ursut, B., Tulin, A. & Constantinoiu, S. Recurrence after hepatic resection in colorectal cancer liver metastasis -Review article. J. Med. Life. 8 (Spec Issue), 12–14 (2015). 26361505 PMC4564049
  3. [3]Guglielmi, A., Ruzzenente, A., Conci, S., Valdegamberi, A. & Iacono, C. How much remnant is enough in liver resection?. Dig Surg. 29 (1), 6–17 (2012). 22441614 · DOI
  4. [4]Helling, T. S. Liver failure following partial hepatectomy. HPB (Oxford). 8 (3), 165–174 (2006). 18333270 PMC2131683 · DOI
  5. [5]Hyder, O. et al. A risk model to predict 90-day mortality among patients undergoing hepatic resection. J. Am. Coll. Surg. 216 (6), 1049–1056 (2013). 23478548 PMC3985272 · DOI
  6. [6]Søreide, J. A. & Deshpande, R. Post hepatectomy liver failure (PHLF)—Recent advances in prevention and clinical management. Eur. J. Surg. Oncol. 47 (2), 216–224 (2021). 32943278 · DOI
  7. [7]Rahbari, N. N. et al. Posthepatectomy liver failure: A definition and grading by the International Study Group of Liver Surgery (ISGLS). Surgery. 149 (5), 713–724 (2011). 21236455 · DOI · Paper page
  8. [8]Martins, P. N., Theruvath, T. P. & Neuhaus, P. Rodent models of partial hepatectomies. Liver Int. 28 (1), 3–11 (2008). 18028319 · DOI
  9. [9]Madrahimov, N., Dirsch, O., Broelsch, C. & Dahmen, U. Marginal hepatectomy in the rat: from anatomy to surgery. Ann. Surg. 244 (1), 89–98 (2006). 16794393 PMC1570604 · DOI
  10. [10]Kubota, T. et al. Minimum sizes for remnant and transplanted livers in rats. J. Hepatobiliary Pancreat. Surg. 4 (4), 398–404 (1997). · DOI
  11. [11]Meier, M. et al. Liver regeneration is dependent on the extent of hepatectomy. J. Surg. Res. 205 (1), 76–84 (2016). 27621002 · DOI
  12. [12]Emond, J. et al. Extent of hepatectomy in the rat. Evaluation of basal conditions and effect of therapy. Eur Surg Res. 21 (5), 251–259 (1989). 2627979 · DOI
  13. [13]Gaub, J. & Iversen, J. Rat liver regeneration after 90% partial hepatectomy. Hepatology 4 (5), 902–904 (1984). 6383999 · DOI
  14. [14]Meier, M. et al. Adaptive growth changes in the liver remnant are affected by the size of hepatectomy in rats. Int. J. Exp. Pathol. 99 (4), 150–157 (2018). 30198172 PMC6157304 · DOI
  15. [15]National Research Council Committee for the Update of the Guide for the C, Use of Laboratory A. The National Academies Collection: Reports funded by National Institutes of Health. Guide for the Care and Use of Laboratory Animals. Washington (DC): National Academies Press (US). Copyright © 2011, National Academy of Sciences.; 2011.
  16. [18]Lund, A. et al. Validation of a surgical model for posthepatectomy liver failure in rats. Anim. Model Exp. Med. 6 (3), 266–273 (2023). PMC10272898 37183349 · DOI
  17. [19]Nyengaard, J. R. Stereologic methods and their application in kidney research. J. Am. Soc. Nephrol. 10 (5), 1100–1123 (1999). 10232698 · DOI
  18. [20]Lafaro, K. et al. Defining post hepatectomy liver insufficiency: Where do we stand?. J Gastrointest. Surg. 19 (11), 2079–2092 (2015). 26063080 · DOI
  19. [21]Zimmermann, H. & Reichen, J. Hepatectomy: Preoperative analysis of hepatic function and postoperative liver failure. Dig Surg. 15 (1), 1–11 (1998). 9845555 · DOI
  20. [22]Walker, V. Ammonia metabolism and hyperammonemic disorders. Adv. Clin. Chem. 67, 73–150 (2014). 25735860 · DOI
  21. [23]Christ, B. et al. Hepatectomy-induced alterations in hepatic perfusion and function—Toward multi-scale computational modeling for a better prediction of post-hepatectomy liver function. Front. Physiol. 12, 733868 (2021). 34867441 PMC8637208 · DOI
  22. [24]Miyaoka, Y. et al. Hypertrophy and unconventional cell division of hepatocytes underlie liver regeneration. Curr. Biol. 22 (13), 1166–1175 (2012). 22658593 · DOI · Paper page
  23. [25]Huang, J. & Rudnick, D. A. Elucidating the metabolic regulation of liver regeneration. Am. J. Pathol. 184 (2), 309–321 (2014). 24139945 PMC3906487 · DOI
  24. [26]Freeman, T. L., Ngo, H. Q. & Mailliard, M. E. Inhibition of system A amino acid transport and hepatocyte proliferation following partial hepatectomy in the rat. Hepatology 30 (2), 437–444 (1999). 10421652 · DOI
  25. [27]Gundersen, H. J. The nucleator. J. Microsc. 151 (Pt 1), 3–21 (1988). 3193456 · DOI
  26. [28]Møller, A., Strange, P. & Gundersen, H. J. Efficient estimation of cell volume and number using the nucleator and the disector. J. Microsc. 159 (Pt 1), 61–71 (1990). 2204703 · DOI
  27. [29]Kuhn, M. A. et al. Abdominal wall repair is delayed during hepatic regeneration. J. Surg. Res. 95 (1), 54–60 (2001). 11120636 · DOI
  28. [30]Brown, D. L. Bias in image analysis and its solution: unbiased stereology. J. Toxicol. Pathol. 30 (3), 183–191 (2017). 28798525 PMC5545670 · DOI
  29. [31]Mühlfeld, C., Nyengaard, J. R. & Mayhew, T. M. A review of state-of-the-art stereology for better quantitative 3D morphology in cardiac research. Cardiovasc. Pathol. 19 (2), 65–82 (2010). 19144544 · DOI

Cited by

Sorted by citations

Authors
Lund, A., Andersen, K. J., Meier, M., Pedersen, M. I., Knudsen, A. R., Kirkegård, J., Mortensen, F. V., & Nyengaard, J. R.
Affiliations
Aarhus University (DK)
Corresponding author
Lund, Andrea
Venue
Scientific Reports
Published
2023-08-19
Volume
13
Issue
1
Pages
13544-13544
ISSN
2045-2322 (ISSN-L)
OpenAlex
W4386002082
Cited by
5
References
1
Citations by year
2026: 1 · 2025: 3 · 2024: 1
FWCI
0.85
Type
journal article
Language
en
Open access
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Arvid Nilssons Fond
  • Købmand Sven Hansen og Hustru Ina Hansens Fond
  • Fabrikant Einar Willumsens Mindelegat
  • Familien Hede Nielsens Fond
  • P. A. Messerschmidt og Hustrus Fond
  • Fonden til Lægevidenskabens Fremme
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
post-hepatectomy liver failure, partial hepatectomy, liver regeneration, hepatocyte proliferation, ammonia metabolism, remnant liver, hepatocyte volume, rat model
MeSH terms
Animals, Hepatectomy, Liver Regeneration, Liver Failure, Hepatic Insufficiency, Rats

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