One liver for four children: first clinical series of liver cell transplantation for severe neonatal urea cycle defects.
BACKGROUND
Urea cycle disorders (UCD) have a poor prognosis despite dietary and pharmacologic therapy, especially if the onset of the disease is within the neonatal period. They are promising target diseases for liver cell transplantation (LCT), which may be a less invasive alternative or supplementation to orthotopic liver transplantation.


METHODS
Cryopreserved hepatocytes were isolated under good manufacturing practice conditions. Four children with severe neonatal UCD (age 1 day-3 years) received multiple intraportal infusions of cryopreserved hepatocytes from that same donor, a 9-day old neonate. Portal vein access was achieved surgically in two children, whereas the umbilical vein was suitable for interventional catheter placement in two neonates. Cell applications were carefully monitored by means of Doppler ultrasound and portal vein pressure.


RESULTS
LCT was feasible in all children. No signs of portal vein thrombosis or extrahepatic shunting were observed. All children showed metabolic stabilization during observation periods of 4 to 13 months. One child with prenatally diagnosed ornithine transcarbamylase deficiency died after 4 months from a fatal metabolic decompensation.


CONCLUSIONS
Given the poor prognosis of UCD with conservative therapy, LCT caused considerable beneficial effects. Periods of hyperammonemia and clinically relevant crises could be reduced during an observation period of up to 13 months. Though cell therapy is not a permanent therapeutic option, bridging to liver transplantation may be substantially improved.
Meyburg
Jochen
J
Department of General Pediatrics, University Children's Hospital, Heidelberg, Germany. jochen.meyburg@med.uni-heidelberg.de
Das
Anibh M
AM
Hoerster
Friederike
F
Lindner
Martin
M
Kriegbaum
Heinz
H
Engelmann
Guido
G
Schmidt
Jan
J
Ott
Michael
M
Pettenazzo
Andrea
A
Luecke
Thomas
T
Bertram
Harald
H
Hoffmann
Georg F
GF
Burlina
Alberto
A
D000641:Ammonia / Q000097:blood; D017690:Cell Transplantation / Q000379:methods*; D015925:Cryopreservation; D022781:Hepatocytes / Q000637:transplantation*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016031:Liver Transplantation / Q000379:methods*; D020163:Ornithine Carbamoyltransferase Deficiency Disease / Q000601:surgery*; D011169:Portal Vein / Q000601:surgery; D014019:Tissue Donors; D016896:Treatment Outcome; D014508:Urea / Q000378:metabolism*
D000641:Ammonia; D014508:Urea