Human Fetal Liver Cell Transplantation for Treatment of Chronic Liver Failure
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 25
- Locations
- 2
- Primary Endpoint
- Patient Survival
Study Overview
Brief Summary
The herein study consists in the transplantation of liver progenitor cells isolated from human fetal liver tissue with the aim of improving conventional liver therapy and broadening therapeutical options other than liver transplantation.
Detailed Description
One of the major clinical problems in transplantation medicine is the discrepancy between the growing number of liver chronic disease patients and the lack of organs. Research and development of new liver failure treatments thus have a high clinical significance. Regenerative medicine and results recently achieved in the field of stem cell biology may provide a remedy to this emerging problem.
Our project aims at developing new generation cell transplantation methodologies through an interdisciplinary research project created from a collaboration between ISMETT, Palermo and the University of Pittsburgh (UPMC-USA).
Adult hepatocyte transplantation has been in use for several years already and has proved to be safe for patients and able, especially in pediatric patients, to improve liver function indices and delay the need for liver transplantation. Studies have been limited until now by the use of already differentiated hepatocytes and therefore unable to proliferate and develop a suitable liver mass to support a decompensated liver.
The hypothesis of our project, supported by in vitro studies and studies on experimental animal models, is based on the possibility to generate an ectopic liver system in the spleen through the experimental use of hepatic cell progenitors obtained from human fetal liver tissues. Human fetal liver cell transplantation will be performed in the spleen through arterial injection.
The final endpoint of the project is to develop an innovative and safe treatment for patients with end-stage chronic liver failure
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Clinical diagnosis (evidence of chronic liver disease, presence of ascites and/or esophageal varices upon superior digestive endoscopy and/or ultrasound evidence of portal hypertension) or histological diagnosis of liver cirrhosis with any etiology.
- •Serious liver failure documented by a score ≥ B8 based on the Child-Pugh-Turcotte classification and/or MELD score ≥
- •Informed consent to the study signed by the patient.
Exclusion Criteria
- •MELD score ≥ 25
- •Hepatocellular carcinoma (HCC)
- •Portal vein thrombosis
- •Serious cardiovascular or respiratory disease, or other medical condition which may threaten patient's life in the subsequent three months
- •Admission to the Intensive Care Unit (ICU)
- •Hemodynamic instability (MAP < 55 mmHg)
- •Use of vasoactive drugs (Epinephrine, Norepinephrine, Vasopressin, Dopamine, Terlipressine
- •Type-1 (acute) hepatorenal syndrome
- •Levels of serum creatinine >2 mg/dl and/or creatinine clearance <30-40 ml/min
- •Sepsis, active infection or spontaneous bacterial peritonitis
- •Active gastrointestinal bleeding or recent gastrointestinal bleeding episode (in the previous 4 weeks)
- •Active alcohol abuse
- •Severe alcoholic hepatitis
- •Pulmonary hypertension (PAP > 35 mmHg)
- •History of neoplasia
- •Pregnancy
- •Non Sicilian residency
- •HBV DNA positive
- •HIV infection
- •Drug addiction
- •Age < 18 years
- •Transjugular intrahepatic portosystemic shunt (TIPS) placed in the previous month
- •Contraindications to the procedure (e.g., related to the splenic artery: aneurysm, kinking, thrombosis, splenic-renal shunt; related to the spleen: large angioma).
Outcomes
Primary Outcomes
Patient Survival
Time Frame: 1 year
Assessment of treated and control patients survival at 1 year follow-up
Secondary Outcomes
- Analysis of Child-Pugh Score From Baseline to 1 Year Follow-up(Baseline and 1 year Follow-up)
- Analysis of Meld Score From Baseline to 1 Year Follow-up(Baseline and 1 year Follow-up)