PLoS ONE (Jan 2013)

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

  • 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

DOI
https://doi.org/10.1371/journal.pone.0053719
Journal volume & issue
Vol. 8, no. 1
p. e53719

Abstract

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ObjectiveImpaired 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.Design58 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.ResultsBoth 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 (pConclusionAutologous 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 registrationControlled-Trials.com ISRCTN83972743.