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Hepatocyte Transplantation for Acute Decompensated Liver Failure

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01345565
Recruitment Status : Withdrawn (A funding mechanism is not identified at this time)
First Posted : May 2, 2011
Last Update Posted : January 23, 2019
Information provided by (Responsible Party):
Ira Fox, University of Pittsburgh

Brief Summary:
The purpose of this research study is to determine whether liver cell transplantation can provide help for patients with liver failure who are unlikely to survive without some form of liver support. The goal of this research study is to determine if liver cell transplants can be effective until a liver transplant is received or until patients recover from their liver failure.

Condition or disease Intervention/treatment Phase
Liver Failure Acute Drug: human hepatocytes Phase 1

Detailed Description:

Orthotopic liver transplantation has become the treatment of choice for patients with acute liver failure with poor prognostic signs. Survival following hepatic transplantation has improved in the last decade for a number of reasons. These include improvement in immunosuppression, improved methods for preserving and transporting organs, use of donors which had been previously considered unacceptable, use of reduced-sized grafts , and the use of living-donor hepatic transplantation. Despite encouraging survival statistics, there continues to be significant morbidity and mortality associated with hepatic transplantation. In addition, the success of hepatic transplantation has broadened the indications for this form of therapy without a concomitant increase in the number of donors available for these patients.

Since the development of a method for isolating primary hepatocytes by collagenase perfusion, many investigators have demonstrated the efficacy of hepatocyte transplantation in the treatment of liver failure and inherited metabolic disorders in experimental animals. Treatment of liver diseases with transplantation of isolated hepatocytes rather than the whole liver has several theoretical advantages. Unlike the whole liver, isolated hepatocytes could be cryopreserved for instant availability and could be modified genetically or otherwise to enhance specific functions, stimulate proliferation or abrogate allograft rejection. Hepatocyte transplantation should be less stressful than whole liver transplantation because the host organ remains intact. Since the transplanted cells integrate into the host liver, they could provide restorative potential and the consequences of graft loss would be relatively minor. In addition, hepatocyte transplantation would not interfere with subsequent liver transplantation, should that become necessary.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Hepatocyte Transplantation for Acute Decompensated Liver Failure
Study Start Date : March 2011
Actual Primary Completion Date : January 2019
Actual Study Completion Date : January 2019

Arm Intervention/treatment
Experimental: Hepatocyte Transplantation
See Below
Drug: human hepatocytes

The intrahepatic site for liver cell transplantation has been associated with the best engraftment and function based on animal experiments. Several approaches for access to the portal vein will be considered. The technique used will be determined based on what is considered best for the child based on risk/benefit at the time.

We propose to attempt to infuse approximately 5-10% of the hepatic mass in order to provide improved hepatic function. Since we do not yet know from our experience so far the correct number of cells to transplant in order to improve function, we will continue to infuse hepatocytes as donors become available until the patient improves to the point where they are no longer meet the criteria for organ transplantation. The subject will be evaluated de novo and if they are a candidate for orthotopic liver transplantation they will receive the transplant.

Primary Outcome Measures :
  1. Improvement in evidence of liver function at two weeks after hepatocyte transplant [ Time Frame: Two weeks after hepatocyte transplant ]
    The extent to which hepatocyte transplantation can elicit evidence of improvement in liver function in patients with acute decompensated liver failure not responding to medical management.

Secondary Outcome Measures :
  1. Immune Response [ Time Frame: two weeks after hepatocyte transplant and monthly thereafter post hepatocyte transplant ]
    The extent to which the standard immune suppression medications used for solid organ transplantation can effectively control rejection and preserve the function of transplanted hepatocytes without leading to overwhelming infection or other medication related toxicities in the face of hepatic failure.

  2. Quality and Quantity of Hepatocytes [ Time Frame: Two weeks after hepatocyte transplant ]
    The relationship between number and quality of donor hepatocytes infused and engraftment in the livers of patients with the acute liver injury.

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Subjects will include those patients with ALF who are potential conventional liver transplant recipient candidates based on PELD criteria as well as those who would not be considered candidates for orthotopic liver transplantation (e.g. patients who appear to be too small or too ill for solid organ transplant or those who have a diagnosis that is a contradiction for whole organ transplantation, for example, systemic mitochondrial hepatopathy).
  • If the patient is a candidate for orthotopic liver transplantation (per standard clinical criteria), they will be officially listed for liver transplantation as well as hepatocyte transplantation.
  • If a subject is a potential conventional liver transplant recipient candidate and a donor liver is available; the patient will receive a solid organ transplant.
  • Subjects ages 0-21 years old will be included in this study.

Exclusion Criteria:

The patient has:

  1. Severe cardiovascular or respiratory disease at baseline and at the time of hepatocyte transplant as defined by

    1. Central venous pressure >25 mm Hg or if known, pulmonary capillary wedge pressure of >30 mg Hg or
    2. Oxygen saturation of <90% on > 60% oxygen OR a P/F ratio (Po2/FiO2) of <1.
  2. Hemodynamically significant gastrointestinal bleeding causing a systolic blood pressure <70mmHg at the time of transplantation.
  3. Uncorrectable coagulopathy despite use of plasmapheresis that would preclude any invasive procedures.
  4. Leukopenia at the time of cell transplant, defined as an absolute neutrophil count of <500/µL.
  5. Known allergy to immunosuppression medications that are required post transplant procedure for the prevention of rejection.
  6. Active malignancy except those with acute liver failure during treatment with estimated life expectancies of >1 year if the malignancy is controlled.
  7. Sepsis or other active infection except those without evidence of hemodynamically significant uncontrollable systemic sepsis with positive blood or tissue cultures.
  8. Intrauterine pregnancy. All females of childbearing potential will receive a pregnancy test prior to enrollment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01345565

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United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15201
Sponsors and Collaborators
Ira Fox
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Principal Investigator: Ira J Fox, MD University of Pittsburgh
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Responsible Party: Ira Fox, Professor of Surgery, University of Pittsburgh Identifier: NCT01345565    
Other Study ID Numbers: PRO09020051
First Posted: May 2, 2011    Key Record Dates
Last Update Posted: January 23, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Ira Fox, University of Pittsburgh:
fulminant hepatic failure
Additional relevant MeSH terms:
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Liver Failure
Hepatic Insufficiency
Liver Diseases
Digestive System Diseases