Liver after hepatocyte transplantation for liver-based metabolic disorders in children.
There are limited data regarding donor hepatocyte engraftment into recipient liver after human hepatocyte transplantation (HHTx). We reviewed the explant livers of seven children with metabolic disorders [ornithine-transcarbamylase deficiency (one), coagulation factor VII deficiency (three), Crigler-Najjar syndrome (one), progressive familial intrahepatic cholestasis type 2 (PFIC-2) deficiency (two)] who received allograft hepatocytes by intraportal infusion with improvement in phenotype, although all later underwent liver transplantation (LT). Immunohistochemistry for bile salt export protein (BSEP) in the PFIC-2 patients and genetic typing following laser capture microdissection (LCM) of liver cells in the others were used to identify donor hepatocytes in recipient explant livers. Explant livers usually showed a preserved lobular architecture. In one patient, hepatocytes were identified inside portal vein thrombi. No donor hepatocytes in liver cell plates were identified immunohistochemically or by genetic typing. HHTx was generally followed by partial recovery of metabolic function; the procedure was well tolerated; any increase in portal vein pressure was transient. Hepatocytes were identified in portal vein thrombi, even months after portal vein infusion. Further studies are needed to monitor donor hepatocytes in vivo, to quantify better the efficacy of the procedure and to find ways of improving engraftment and function.
Institute of Liver Studies, King's College Hospital and King's College London School of Medicine, London, UK.
Alberto
A
Quaglia
Sharon C
SC
Lehec
Robin D
RD
Hughes
Ragai R
RR
Mitry
A S
AS
Knisely
Stephen
S
Devereaux
Julie
J
Richards
Mohamed
M
Rela
Nigel D
ND
Heaton
Bernard C
BC
Portmann
Anil
A
Dhawan
D001284:Atrophy; D001707:Biopsy, Needle; D001794:Blood Pressure; D002469:Cell Separation / Q000379:methods; D017690:Cell Transplantation / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D022781:Hepatocytes / Q000166:cytology / Q000473:pathology / Q000637:transplantation*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008107:Liver Diseases / Q000473:pathology / Q000601:surgery*; D008297:Male; D008659:Metabolic Diseases / Q000473:pathology / Q000601:surgery*; D011168:Portal System / Q000502:physiology; D014019:Tissue Donors
D004247:DNA