Autologous bone marrow mononuclear cell transplantation in patients with decompensated alcoholic liver disease: a randomized controlled trial.

<h4>Objective</h4>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.<h4>Design&...

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Autores principales:	Laurent Spahr, Yves Chalandon, Sylvain Terraz, Vincent Kindler, Laura Rubbia-Brandt, Jean-Louis Frossard, Romain Breguet, Nicolas Lanthier, Annarita Farina, Jakob Passweg, Christoph D Becker, Antoine Hadengue
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0c0b1305d41a4679a7a3450c1a5ce16c
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spelling	oai:doaj.org-article:0c0b1305d41a4679a7a3450c1a5ce16c2021-11-18T08:01:37ZAutologous bone marrow mononuclear cell transplantation in patients with decompensated alcoholic liver disease: a randomized controlled trial.1932-620310.1371/journal.pone.0053719https://doaj.org/article/0c0b1305d41a4679a7a3450c1a5ce16c2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23341981/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Objective</h4>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.<h4>Design</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>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.<h4>Trial registration</h4>Controlled-Trials.com ISRCTN83972743.Laurent SpahrYves ChalandonSylvain TerrazVincent KindlerLaura Rubbia-BrandtJean-Louis FrossardRomain BreguetNicolas LanthierAnnarita FarinaJakob PasswegChristoph D BeckerAntoine HadenguePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e53719 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Laurent Spahr Yves Chalandon Sylvain Terraz Vincent Kindler Laura Rubbia-Brandt Jean-Louis Frossard Romain Breguet Nicolas Lanthier Annarita Farina Jakob Passweg Christoph D Becker Antoine Hadengue Autologous bone marrow mononuclear cell transplantation in patients with decompensated alcoholic liver disease: a randomized controlled trial.
description	<h4>Objective</h4>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.<h4>Design</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>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.<h4>Trial registration</h4>Controlled-Trials.com ISRCTN83972743.
format	article
author	Laurent Spahr Yves Chalandon Sylvain Terraz Vincent Kindler Laura Rubbia-Brandt Jean-Louis Frossard Romain Breguet Nicolas Lanthier Annarita Farina Jakob Passweg Christoph D Becker Antoine Hadengue
author_facet	Laurent Spahr Yves Chalandon Sylvain Terraz Vincent Kindler Laura Rubbia-Brandt Jean-Louis Frossard Romain Breguet Nicolas Lanthier Annarita Farina Jakob Passweg Christoph D Becker Antoine Hadengue
author_sort	Laurent Spahr
title	Autologous bone marrow mononuclear cell transplantation in patients with decompensated alcoholic liver disease: a randomized controlled trial.
title_short	Autologous bone marrow mononuclear cell transplantation in patients with decompensated alcoholic liver disease: a randomized controlled trial.
title_full	Autologous bone marrow mononuclear cell transplantation in patients with decompensated alcoholic liver disease: a randomized controlled trial.
title_fullStr	Autologous bone marrow mononuclear cell transplantation in patients with decompensated alcoholic liver disease: a randomized controlled trial.
title_full_unstemmed	Autologous bone marrow mononuclear cell transplantation in patients with decompensated alcoholic liver disease: a randomized controlled trial.
title_sort	autologous bone marrow mononuclear cell transplantation in patients with decompensated alcoholic liver disease: a randomized controlled trial.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/0c0b1305d41a4679a7a3450c1a5ce16c
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Autologous bone marrow mononuclear cell transplantation in patients with decompensated alcoholic liver disease: a randomized controlled trial.

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