title: First example of hepatocyte transplantation to alleviate ornithine transcarbamylase deficiency, monitored by NMR-based metabonomics.
abstract: We demonstrate the effective use of NMR spectroscopic profiles of urine and plasma from the first successful use of hepatocyte transplantation as a bridge to auxiliary partial orthotopic liver transplantation in a child antenatally diagnosed with severe ornithine transcarbamylase deficiency. In this single-patient study, NMR profiles indicated that the disrupted urea cycle could be normalized by hepatocyte cell infusion and this was confirmed using orthogonal partial least-squares-based chemometrics. However, despite dietary manipulations and adminstration of ammonia scavengers, the desired reduction in plasma ammonia was not consistently achieved between sessions of hepatocyte transplantation due to episodes of sepsis. A subsequent liver transplant corrected the metabolic abnormalities. The use of metabolic profiling has been shown to be a promising method for evaluating the efficacy of cell infusions and has demonstrated the capability for the early detection of response to therapy in real time, an approach that may be of use in wider clinical settings.
authors.affiliation: Department of Biomolecular Medicine, Faculty of Medicine, Sir Alexander Fleming Building, Imperial College, London, UK. cristina.legido_quigley@kcl.ac.uk
authors.forename: Cristina
authors.initials: C
authors.lastname: Legido-Quigley
authors.forename: Olivier
authors.initials: O
authors.lastname: Cloarec
authors.forename: David A
authors.initials: DA
authors.lastname: Parker
authors.forename: Gerard M
authors.initials: GM
authors.lastname: Murphy
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
authors.forename: John C
authors.initials: JC
authors.lastname: Lindon
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
authors.forename: Ragai R
authors.initials: RR
authors.lastname: Mitry
authors.forename: Hector
authors.initials: H
authors.lastname: Vilca-Melendez
authors.forename: Mohamed
authors.initials: M
authors.lastname: Rela
authors.forename: Anil
authors.initials: A
authors.lastname: Dhawan
authors.forename: Nigel
authors.initials: N
authors.lastname: Heaton
mesh_terms: D000641:Ammonia / Q000097:blood / Q000652:urine; D022781:Hepatocytes / Q000502:physiology / Q000637:transplantation*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016031:Liver Transplantation; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008991:Monitoring, Physiologic / Q000379:methods*; D009154:Mutation; D020163:Ornithine Carbamoyltransferase Deficiency Disease / Q000097:blood / Q000601:surgery* / Q000652:urine; D018805:Sepsis / Q000097:blood / Q000175:diagnosis / Q000652:urine; D016896:Treatment Outcome; D014508:Urea / Q000097:blood / Q000652:urine
chemical_list: D000641:Ammonia; D014508:Urea