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Hepatocyte transplantation (HT) has become an effective therapy for patients with metabolic inborn errors. We report the clinical outcome of four children with metabolic inborn errors that underwent HT, describing the cell infusion protocol and the metabolic outcome of transplanted patients. Cryopreserved hepatocytes were used as this allows scheduling of treatments. Functional competence (viability, cell attachment, major cytochrome P450 and UDP-glucuronosyltransferase 1A1 activities, and urea synthesis) and microbiological safety of cell batches were assessed prior to clinical use. Four pediatric patients with liver metabolic diseases [ornithine transcarbamylase (OTC) deficiency, Crigler–Najjar (CNI) syndrome, glycogen storage disease Ia (GSD-Ia), and tyrosinemia type I (TYR-I)] underwent HT. Indication for HT was based on severity of disease, deterioration of quality of life, and benefits for the patients, with the ultimate goal to improve their clinical status whenever liver transplantation (LT) was not indicated or to bridge LT. Cells were infused into the portal vein while monitoring portal flow. The protocol included antibiotic prophylaxis and immunosuppressant therapy. After HT, analytical data on the disease were obtained. The OTC-deficient patient showed a sustained decrease in plasma ammonia levels and increased urea production after HT. Further cell infusions could not be administered given a fatal nosocomial fungus sepsis 2 weeks after the last HT. The CNI and GSD-Ia patients improved their clinical status after HT. They displayed reduced serum bilirubin levels (by ca. 50%) and absence of hypoglycaemic episodes, respectively. In both cases, the HT contributed to stabilize their clinical status as LT was not indicated. In the infant with TYR-I, HT stabilized temporarily the biochemical parameters, resulting in the amelioration of his clinical status while diagnosis of the disease was unequivocally confirmed by full gene sequencing. In this patient, HT served as a bridge therapy to LT.

To assay the efficiency for celiac disease (CD) screening of 2 immunochromatographic visual stick assays based on human recombinant tissue transglutaminase (tTG). One was the antitissue transglutaminase antibodies (AtTGA) stick for IgA/G antibodies to tTG detection, the other was the AtTGA/antigliadin antibodies (AGA) stick for IgA antibodies for tTG and/or gliadins.

To assay the efficiency for celiac disease (CD) screening of 2 immunochromatographic visual stick assays based on human recombinant tissue transglutaminase (tTG). One was the antitissue transglutaminase antibodies (AtTGA) stick for IgA/G antibodies to tTG detection, the other was the AtTGA/antigliadin antibodies (AGA) stick for IgA antibodies for tTG and/or gliadins. In a prospective multicenter study, 4 pediatric gastroenterology units from Spain and 2 from Latin America enrolled 72 control children with a normal small bowel mucosa and 113 untreated patients with CD with Marsh type 3 lesions. Evaluation of results by the gastroenterologists and by 2 independent observers at the coordination center showed a remarkably low interobserver variability. For the AtTGA stick, sensitivity was 96.5% and specificity was 98.6%. The AtTGA/AGA stick displayed a sensitivity of 94.5% and a specificity of 98.6% for AtTGA and a sensitivity of 63.1% and a specificity of 95.2% for AGA. The highest efficiency and positive likelihood ratio was obtained for the AtTGA stick, higher than for IgA AtTGA by enzyme-linked immunosorbent assay. One additional advantage was that previous investigation of total serum IgA levels could be eluded. The IgA AtTGA/AGA stick, with an efficiency of 95.1%, compared with 89.2% when the combined results of the 2 enzyme-linked immunosorbent assays were considered, turned out to be an excellent diagnostic tool for infants with no IgA deficiency. These 2 assays are extremely efficient for CD screening, by combining a high diagnostic accuracy with the simplicity and rapidity of visual methods.