Hepatocyte Transplantation for Acute Decompensated Liver Failure

Phase 1

Withdrawn

• Conditions: Liver Failure Acute
• Interventions: Drug: human hepatocytes

• Registration Number: NCT01345565
• Lead Sponsor: Ira Fox

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.

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.

Study Timeline

• Study Start: 2011-03
• Study First Submitted: 2011-04-26
• Study First Submitted QC: 2011-04-28
• Study First Posted: 2011-05-02
• Status Verified: 2019-01
• Primary Completion: 2019-01
• Study Completion: 2019-01
• Last Update Submitted: 2019-01-18
• Last Update Posted: 2019-01-23

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Hepatocyte Transplantation	human hepatocytes	See Below

Primary Outcome Measures

Name	Time	Method
Improvement in evidence of liver function at two weeks after hepatocyte transplant	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

Name	Time	Method
Immune Response	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.
Quality and Quantity of Hepatocytes	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.

Trial Locations

Locations (1)

Children's Hospital of Pittsburgh of UPMC; 🇺🇸 Pittsburgh, Pennsylvania, United States