1527 ISSN 1757-6180 Bioanalysis (2009) 1(9), 1527–1535 10.4155/BIO.09.112 © 2009 Future Science Ltd ReseaRch aRticle Interest in hepatocyte transplantation has been growing continuously in recent years and this treatment might represent an alternative clini- cal approach for patients with acute liver fail- ure and liver-based metabolic disorders, such as ornithine transcarbamylase deficiency (OTC) [1] . OTC is the most common urea cycle defect observed in humans and it can be a life-threat- ening X-linked inborn error of metabolism. It results in impaired urea formation and the ele- vation of endogenous ammonia, in severe cases to fatal levels. The indication and timing for liver transplantation in such metabolic disorders depends on the underlying cause. Some meta- bolic disorders cause progressive liver injury, eventually leading to cirrhosis [2] . In severe metabolic cases, it has been recommended that auxiliary partial orthotopic liver transplantation (APOLT) be made as early as possible to avoid liver failure [3,4] . Even in less-severe cases, when treated with nitrogen scavengers, impairment of the urea cycle leads to reduced bioavailability of de novo ornithine and arginine. Isolated dietary interventions are generally ineffective and so the use of liver cell infusions to replenish the deicient liver enzymes has been proposed [5–7] . For both cell and liver transplantation, there is a critical need to monitor and evaluate graft function and the biochemical effect of therapy. NMR-based metabonomic techniques can help to follow therapeutic response, since the use of 1 H NMR spectroscopy as a method for determin- ing proiles of endogenous metabolites present in bioluids such as urine, blood plasma and, more recently, intact tissues is well established [8–11] . As such, the technique has been widely employed in the characterization of the metabolic conse- quences of disease or toxic insult [12–15] and to several inborn errors of metabolism [16,17] . When combined with advanced methods of data pro- cessing and chemometrics, it has proved to be a useful method for disease diagnosis and biomarker identiication [18] . This case study describes the use of 1 H NMR spectroscopy-based metabonomics to assess the metabolic consequences of the irst com- bined treatment by hepatocyte infusion and APOLT performed on an infant with severe OTC deiciency. Materials & methods  Patient An 18-year-old full-term primigravida, asymp- tomatic and heterozygous for OTC deiciency, was referred to the Pediatric Liver Centre. There was a signiicant history of OTC deiciency in her family. Her brother and niece had died within the irst week of life of hyperammone- mic encephalopathy and severe cerebral edema. She was pregnant with a male fetus and the mutation IVS7 + 3A>G had been identiied in a fetal blood sample, conirming the diagnosis of OTC deiciency. The infant was delivered at term in good condition (Apgar scores of 9 at 1 min and 10 at 5 min) with a birth weight of 3.85 kg. The initial blood ammonia level was First example of hepatocyte transplantation to alleviate ornithine transcarbamylase deiciency, monitored by NMR-based metabonomics We demonstrate the effective use of NMR spectroscopic proiles of urine and plasma from the irst successful use of hepatocyte transplantation as a bridge to auxiliary partial orthotopic liver transplantation in a child antenatally diagnosed with severe ornithine transcarbamylase deiciency. In this single-patient study, NMR proiles indicated that the disrupted urea cycle could be normalized by hepatocyte cell infusion and this was conirmed 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 proiling has been shown to be a promising method for evaluating the eficacy 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. Cristina Legido-Quigley 1,4† , Olivier Cloarec 1 , David A Parker 1 , Gerard M Murphy 1 , Elaine Holmes 1 , John C Lindon 1 , Jeremy K Nicholson 1 , Ragai R Mitry 2 , Hector Vilca-Melendez 2 , Mohamed Rela 2 , Anil Dhawan 3 & Nigel Heaton 2† † Authors for correspondence 1 Department of Biomolecular Medicine, Faculty of Medicine, Sir Alexander Fleming Building, Imperial College, London, UK E-mail: cristina.legido_quigley@ kcl.ac.uk 2 Liver Transplant Surgical Service, Institute of Liver Studies, King’s College Hospital, Denmark Hill, London, UK E-mail: nigel.heaton@kch.nhs.uk 3 Paediatric Liver Centre, King’s College Hospital, Denmark Hill, London, UK 4 Pharmaceutical Science Division, King’s College London, UK For reprint orders, please contact reprints@future-science.com