Human Fetal Liver Cell Transplantation in Chronic Liver Failure (hFLCTx)

The Mediterranean Institute for Transplantation and Advanced Specialized Therapies

Status and phase

Completed

Phase 2

Phase 1

Conditions

Liver Cirrhosis

Treatments

Other: Human Fetal Liver Cell Transplantation

Study type

Interventional

Funder types

Other

Identifiers

NCT01013194

IRRB/01/06

Details and patient eligibility

About

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.

Full 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

Enrollment

25 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

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 ≥ 14.
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).