Markers of liver regeneration—the role of growth factors and cytokines: a systematic review
Open accessAbstract
BACKGROUND: Post-hepatectomy liver failure contributes significantly to postoperative mortality after liver resection. The prediction of the individual risk for liver failure is challenging. This review aimed to provide an overview of cytokine and growth factor triggered signaling pathways involved in liver regeneration after resection. METHODS: MEDLINE and Cochrane databases were searched without language restrictions for articles from the time of inception of the databases till March 2019. All studies with comparative data on the effect of cytokines and growth factors on liver regeneration in animals and humans were included. RESULTS: Overall 3.353 articles comprising 40 studies involving 1.498 patients and 101 animal studies were identified and met the inclusion criteria. All included trials on humans were retrospective cohort/observational studies. There was substantial heterogeneity across all included studies with respect to the analyzed cytokines and growth factors and the described endpoints. CONCLUSION: High-level evidence on serial measurements of growth factors and cytokines in blood samples used to predict liver regeneration after resection is still lacking. To address the heterogeneity of patients and potential markers, high throughput serial analyses may offer a method to predict an individual's regenerative potential in the future.
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The insulin-like growth factor pathway significantly influences hepatocyte survival and proliferation, acting as a growth-promoting and protective factor.
“The insulin-like growth factor (IGF) pathway significantly influences hepatocyte survival and proliferation, acting as a growth-promoting and protective factor.”
From Liver regeneration after partial hepatectomy: Triggers and mechanisms (2025) · cites this paper as [63]
The Results > Growth factors section says IGF-2 promotes hepatocyte proliferation and tissue repair during chronic liver injury. It also describes IGFs as growth-promoting and involved in inhibiting apoptosis, but specifies that the latter finding concerns various cells, not hepatocytes specifically. The review says the IGF system’s role in injured liver remains incompletely understood, so the claim’s unqualified assertion of a protective effect on hepatocyte survival goes beyond the evidence presented. (LLM, conf=0.83)
Experimental — accuracy not yet measuredEGF, FGF and PDGF play a major role in liver regeneration and are closely linked to dedifferentiation events during hepatocyte proliferation.
“It is known, that EGF, FGF and PDGF play a major role in liver regeneration and therefore are closely linked to dedifferentiation events during hepatocyte proliferation (Hoffmann et al., 2020[18]).”
From Optimization of extracellular matrix for primary human hepatocyte cultures using mixed collagen-matrigel matrices (2023) · cites this paper as Hoffmann et al., 2020[18]
The Results > Growth factors section links EGF and FGF signaling to hepatocyte proliferation and describes PDGF signaling as significant, though replaceable, in liver regeneration. The Results > Temporal sequence of regeneration section also places these factors in the regenerative response. Neither section links them to hepatocyte dedifferentiation; a search for that link found no supporting passage. (LLM, conf=0.88)
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- Authors
- Hoffmann, K., Nagel, A. J., Tanabe, K., Fuchs, J., Dehlke, K., Ghamarnejad, O., Lemekhova, A., & Mehrabi, A.
- Affiliations
- Heidelberg University (DE)
- Corresponding author
- Hoffmann, Katrin
- Venue
- BMC Surgery
- Published
- 2020-02-12
- Volume
- 20
- Issue
- 1
- Pages
- 31-31
- ISSN
- 1471-2482 (ISSN-L)
- PMC
- PMC7017496
- OpenAlex
- W3008927934
- Cited by
- 94
- References
- 189
- Citations by year
- 2026: 7 · 2025: 20 · 2024: 10 · 2023: 19 · 2022: 15 · 2021: 16 · 2020: 7
- FWCI
- 1.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- BMC Surgery (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Deutsche Forschungsgemeinschaft
- Universität Heidelberg
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Keywords
- liver regeneration, post-hepatectomy liver failure, cytokines, growth factors, hepatectomy, signaling pathways, risk prediction
- MeSH terms
- Animals, Hepatectomy, Humans, Liver, Liver Regeneration, Postoperative Period, Biomarkers, Cytokines
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 ›
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