ArticleHepatology international2019
Cellular and functional loss of liver endothelial cells correlates with poor hepatocyte regeneration in acute-on-chronic liver failure.
Article in Hepatology international, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- Acute-on-Chronic Liver Failure: An Eroded Cliff Hit by a Storm-A Narrative Review.International journal of molecular sciences · 2026Review
- Acute-on-chronic liver failure-associated CD45Cellular and molecular life sciences : CMLS · 2026Article
- Acute-on-chronic liver failure: pathophysiological mechanisms and clinical management.Nature reviews. Gastroenterology & hepatology · 2026Review
- Genetic and pharmaceutical manipulation of H3K9 methyltransferase Suv39h1 promotes liver regeneration by unleashing HMGB2 transcription.Experimental & molecular medicine · 2026Article
- Antibiotic exposure exacerbates acute-on-chronic liver failure via gut microbiota imbalance and secondary liver lesion.Journal of medical microbiology · 2026Article
- Cell therapy for liver disorders: past, present and future.Nature reviews. Gastroenterology & hepatology · 2025Review
- Potential therapies for acute-on-chronic liver failure.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Utilising an in silico model to predict outcomes in senescence-driven acute liver injury.NPJ Regenerative medicine · 2024Article
- Review
- The Immunoregulatory and Regenerative Potential of Activated Human Stem Cell Secretome Mitigates Acute-on-Chronic Liver Failure in a Rat Model.International journal of molecular sciences · 2024Article
- Rejuvenating bone marrow hematopoietic reserve prevents regeneration failure and hepatic decompensation in animal model of cirrhosis.Frontiers in immunology · 2024Article
- Novel Therapeutic Approaches in Treatment of Acute-on-Chronic Liver Failure.Seminars in liver disease · 2023Review
- EASIX Is an Accurate and Easily Available Prognostic Score in Critically Ill Patients with Advanced Liver Disease.Journal of clinical medicine · 2023Article
- Exploration and verification of COVID-19-related hub genes in liver physiological and pathological regeneration.Frontiers in bioengineering and biotechnology · 2023Article
- Responses of hepatic sinusoidal cells to liver ischemia-reperfusion injury.Frontiers in cell and developmental biology · 2023Review
- Cirrhosis-associated immune dysfunction.Nature reviews. Gastroenterology & hepatology · 2022Review
- Cirrhosis-Based Acute-on-Chronic Liver Failure Is Marked by Inflammation and Impaired Liver Regeneration Despite Stat3 Activation.Gastro hep advances · 2022Article
- Bioenergetic Failure Drives Functional Exhaustion of Monocytes in Acute-on-Chronic Liver Failure.Frontiers in immunology · 2022Article
- HGF/c-Met: A Key Promoter in Liver Regeneration.Frontiers in pharmacology · 2022Review
- Establishment of a murine model of acute-on-chronic liver failure with multi-organ dysfunction.Hepatology international · 2021Article
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND AND
aimAcute hepatic insult triggers regeneration. If acute-on-chronic liver failure (ACLF) patients have a poorer regenerative response than acute liver failure (ALF) patients, and if so, the mechanisms underlying this, are not well understood.
methodsWe investigated the status of hepatocyte proliferation, hepatic progenitor cell (HPC) mediated regeneration, non-parenchymal cells (through immunohistochemistery), cytokines and growth factors (cytokine bead array) in liver and peripheral blood of ACLF (n = 29) and ALF (n = 17) patients. Liver endothelial cells, mesenchymal cells and Kupffer cells were isolated from explant livers and analysis of regenerative factors was done by qRT-PCR.
resultsUnlike ALF, the ACLF livers showed decreased hepatocyte proliferation (p < 0.001) and profound ductular-reaction with increased CK19 + hepatocytes (p < 0.0001). However, only decrease in Ki67+ hepatocytes was associated with 28 day mortality in ACLF (p < 0.001; HR = 0.78; 95% CI 0.69-0.88). In both groups, increase in plasma hepatocyte growth factor (HGF) (OR = 21.87 p = 0.002;), macrophage colony stimulating factor (MCSF) (OR = 21.73; p = 0.002) and stromal derived factor (SDF1)(OR = 10.2; p = 0.001) were associated with hepatocyte proliferation and decreased (> fivefolds) levels were associated with poor hepatocyte regeneration in ACLF patients. ACLF livers showed decrease in endothelial cells (p < 0.01) and expression of regenerative angiocrine factors C-X-C chemokine receptor type 7 (CXCR7), Inhibitor of DNA Binding 1(IDI) and HGF compared to ALF. In co-culture, while ALF liver mesenchymal stromal cells (LMSCs) induced the expression of CXCR7, IDI and HGF in human umbilical cord endothelial cells (HUVECs), the ACLF LMSCs were defective and showed decreased production of SDF-1, HGF and MCSF compared to ALF.
conclusionsDecrease in hepatic endothelial cells and their regenerative angiocrine functions indicated by defective CXCR7-ID1 dependent HGF expression underlie the poor hepatocyte proliferation in ACLF compared to ALF patients. A robust hepatocyte self-replication is lacking in the livers of ACLF patients and is associated with poor survival.
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