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Autologous Bone Marrow Mononuclear Cell Transplantation in Patients with Decompensated Alcoholic Liver Disease: A Randomized Controlled Trial
Open accessAbstract
OBJECTIVE: Impaired liver regeneration is associated with a poor outcome in patients with decompensated alcoholic liver disease (ALD). We assessed whether autologous bone marrow mononuclear cell transplantation (BMMCT) improved liver function in decompensated ALD. DESIGN: 58 patients (mean age 54 yrs; mean MELD score 19, all with cirrhosis, 81% with alcoholic steatohepatitis at baseline liver biopsy) were randomized early after hospital admission to standard medical therapy (SMT) alone (n = 30), including steroids in patients with a Maddrey's score ≥32, or combined with G-CSF injections and autologous BMMCT into the hepatic artery (n = 28). Bone marrow cells were harvested, isolated and reinfused the same day. The primary endpoint was a ≥3 points decrease in the MELD score at 3 months, corresponding to a clinically relevant improvement in liver function. Liver biopsy was repeated at week 4 to assess changes in Ki67+/CK7+ hepatic progenitor cells (HPC) compartment. RESULTS: Both study groups were comparable at baseline. After 3 months, 2 and 4 patients died in the BMMCT and SMT groups, respectively. Adverse events were equally distributed between groups. Moderate alcohol relapse occurred in 31% of patients. The MELD score improved in parallel in both groups during follow-up with 18 patients (64%) from the BMMCT group and 18 patients (53%) from the SMT group reaching the primary endpoint (p = 0.43 (OR 1.6, CI 0.49-5.4) in an intention to treat analysis. Comparing liver biopsy at 4 weeks to baseline, steatosis improved (p<0.001), and proliferating HPC tended to decrease in both groups (-35 and -33%, respectively). CONCLUSION: Autologous BMMCT, compared to SMT is a safe procedure but did not result in an expanded HPC compartment or improved liver function. These data suggest either insufficient regenerative stimulation after BMMCT or resistance to liver regenerative drive in patients with decompensated alcoholic cirrhosis. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN83972743.
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“Another clinical trial in decompensated alcoholic cirrhosis (DAC) also indicated that the combination of BM-MNCs with standard medical therapy (SMT) did not show superiority over SMT alone [53].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [53]
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“Furthermore, this approach, which included G-CSF mobilization, failed to stimulate LPC expansion or promote liver regeneration [53].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [53]
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Metadata
- Authors
- Spahr, L., Chalandon, Y., Terraz, S., Kindler, V., Rubbia-Brandt, L., Frossard, J.-L., Breguet, R., Lanthier, N., Farina, A., Passweg, J., Becker, C. D., & Hadengue, A.
- Affiliations
- University Hospital of Geneva (CH)
- Corresponding author
- Spahr, Laurent
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-01-14
- Volume
- 8
- Issue
- 1
- Pages
- e53719
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3544843
- OpenAlex
- W1985534351
- Cited by
- 118
- References
- 50
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 2 · 2023: 7 · 2022: 12 · 2021: 6 · 2020: 7 · 2019: 11 · 2018: 10 · 2017: 9 · 2016: 13 · 2015: 11 · 2014: 12 · 2013: 7
- FWCI
- 8.92
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
- Digital Access to Libraries (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- American Association for the Study of Liver Diseases
- Louis-Jeantet Foundation
- Faculté de Médecine, Université de Genève
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- autologous bone marrow mononuclear cell transplantation, alcoholic cirrhosis, alcoholic steatohepatitis, liver regeneration, hepatic progenitor cells, MELD score, granulocyte colony-stimulating factor, liver function, alcohol relapse
- MeSH terms
- Adolescent, Adult, Aged, Female, Hepatic Artery, Humans, Liver, Liver Diseases, Alcoholic, Male, Middle Aged, Regeneration, Time Factors, Transplantation, Autologous, Biomarkers, Bone Marrow Transplantation, Cytokines, Recovery of Function, Hepatocytes, Stem Cell Transplantation, Cell Proliferation, Young Adult
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