Clinical Trial: The Effectiveness and Safety for Mesenchymal Stem Cell for Alcoholic Liver Cirrhosis

Study Status: Completed
Recruit Status: Unknown status
Study Type: Interventional

Official Title: The Evaluation of Effectiveness and Safety for New Therapy With Bone Marrow Derived Autologous Mesenchymal Stem Cell for Hepatic Failure Caused by Alcoholic Liver Cirrhosis

Brief Summary:

Background & Aim: Bone marrow derived mesenchymal stem cells (BM-MSCs) have capacity to differentiate into hepatocytes and anti-fibrotic effect in the experimental model. No study was done in humans with alcoholic liver cirrhosis. The researchers investigated the anti-fibrotic effect of BM-MSCs in alcoholic cirrhosis as Phase II clinical study.

Methods: Eleven alcoholic cirrhosis patients (M:F = 10:1) with Child-Pugh's class B and maintenance of alcohol abstinence at least 2 months were enrolled. At baseline, all patients received liver biopsy, hepatic venous pressure gradient (HVPG) measurement and serologic tests. BM-MSCs were isolated from each patient's BM and amplified for one month and injected two times at 4, 8week through Rt. hepatic artery. 5x106cells/mL of BM-MSCs were injected in each session. Follow up biopsy, HVPG and relative expression of tissue transforming growth factor-1 (TGF-β1), α smooth muscle actin (α-SMA) and collagen-1 by real time RT PCR were measured after 12weeks from 2nd BM-MSC injection. The primary outcome was improvement in patients' histology Aim :

The researchers aimed to evaluate safety and effectiveness of new therapy with bone marrow derived autologous mesenchymal stem cell for hepatic failure caused by alcoholic liver cirrhosis.


Detailed Summary: Autologous BM-MSCs therapy in alcoholic cirrhosis induces improvement of hepatic fibrosis in histological and quantitative measurements.
Sponsor: Yonsei University

Current Primary Outcome: The improvement of Liver Histologic grade [ Time Frame: 6 months later ]

according to Metavir and Laennec fibrosis scoring system


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • The evaluation of hepatic dendritic cells activity by immunohistochemistry [ Time Frame: baseline and 6 months later ]
  • Liver fibrosis quantitative analysis using Hydroxyproline contents in liver tissue [ Time Frame: baseline and 6 months later ]
    Hydroxyproline is a essential component of collange fiber
  • Real-Time Polymerase Chain Reaction for relative mRNA expression of TGF-beta, collagen, procollagen, MMP2 or 9 [ Time Frame: baseline and 6 months later ]
  • Hepatic venous pressure gradient(HVPG) [ Time Frame: baseline and 6 months later ]
    HVPG is a gold standard to measure the portal hypertension.
  • Hepatic vein arrival time using microbubble contrast enhanced ultrasonography [ Time Frame: baseline and 6 months later ]
    Hepatic vein arrival time is related with portal hypertension and intrahepatic inflammation, neoangiogenesis and shunts formation secondary to hepatic fibrosis.
  • Liver stiffness measurement with transient elastography [ Time Frame: baseline and 6 months later ]
    Recently, hepatic fibrosis can be estimated non-invasively using transient elastography (Fibroscan, commercial name) and it can be additive data in estimation of therapeutic response.
  • Child-Pugh score [ Time Frame: baseline and 6 months later ]
  • MELD score [ Time Frame: baseline and 6 months later ]


Original Secondary Outcome:

  • The evaluation of hepatic dendritic cells activity by immunohistochemistry [ Time Frame: baseline and 6 months later ]
  • Liver fibrosis quantitative analysis(Hydroxyproline) [ Time Frame: baseline and 6 months later ]
  • Real-Time Polymerase Chain Reaction (TGF-beta, collagen, procollagen, MMP2 or 9) [ Time Frame: baseline and 6 months later ]
  • Hepatic vein pressure gradient [ Time Frame: baseline and 6 months later ]
  • Hepatic vein arrival time [ Time Frame: baseline and 6 months later ]
  • Fibroscan [ Time Frame: baseline and 6 months later ]
  • Child-Pugh score [ Time Frame: baseline and 6 months later ]
  • MELD score [ Time Frame: baseline and 6 months later ]
  • The change of ascites [ Time Frame: baseline and 6months later ]


Information By: Yonsei University

Dates:
Date Received: November 10, 2011
Date Started: September 2009
Date Completion: August 2013
Last Updated: December 7, 2012
Last Verified: December 2012