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• W1493149511 abstract "We performed hepatocyte transplantation (HT) in an 11-day-old infant with ornithine transcarbamylase deficiency (OTCD). We used cryopreserved hepatocytes prepared from remnant liver tissue, a byproduct of a hyper-reduced left lateral segment from living donor liver transplantation (LDLT). The patient exhibited hypothermia, drowsiness, and apnea at 3 days of age; these symptoms were accompanied by hyperammonemia (1940 μg/dL at maximum), although there were no abnormalities at birth or an obvious family history (Fig. 1). Further examinations confirmed that the hyperammonemia was the result of OTCD. Multimodal treatments, including alimentotherapy, medications, and continuous hemodiafiltration (CHDF), did not improve the patient's clinical state, and severe hyperammonemia attacks recurred. Because of the patient's small body size (2550 g) and the lack of an available liver donor, HT was indicated. Hepatocytes of the same blood type were chosen from an institutional repository of cryopreserved hepatocytes prepared from the remnant tissue of segment III from unrelated living donors. Thawed hepatocytes were transplanted twice at 11 and 14 days of age with a double-lumen catheter inserted into the left portal vein via the umbilical vein (Fig. 2). The amounts of transplanted hepatocytes were 7.4 × 107 and 6.6 × 107 cells/body, and the viability rates were 89.1% and 82.6%, respectively. The portal flow was kept stable at greater than 10 mL/kg/minute, and the pressure was maintained at less than 20 mm Hg during and after HT. The immunosuppressive treatment followed the same protocol used for LDLT with tacrolimus and low-dose steroids.1 The patient was weaned from CHDF and the ventilator at 26 and 30 days of age, respectively, with a stable serum ammonia level of 40 μg/dL. The patient was ultimately discharged 56 days after HT. During the 3 months of follow-up, the baby did well with protein restriction (2 g/kg/day), medication for OTCD, and immunosuppression. No neurological sequelae related to hyperammonemia have been observed so far (Fig. 1). For children with metabolic liver disease, HT is indicated as an alternative or bridge to liver transplantation.2 HT is less invasive than liver transplantation and can be performed repeatedly. Limitations to the widespread application of HT include the poor availability of hepatocytes. Therefore, it is important to find new sources of high-quality hepatocytes. We previously prepared a repository of hepatocytes obtained from remnant liver tissue, a byproduct of hyper-reduced left lateral segmentectomy in LDLT.1 The cell donor was an unrelated volunteer with the same blood type who had previously undergone hyper-reduced left lateral segmentectomy. The main unit of segment II was used as a monosegmental liver graft for the primary recipient with end-stage liver disease, and the remnant was used to isolate hepatocytes with fully informed consent. The hepatocytes were isolated according to the collagenase perfusion method, as described elsewhere,3 with Liberase MTF C/T GMP grade (Roche). All procedures were performed at our cell processing center according to a strictly controlled protocol based on good manufacturing practices. The total number of transplanted live hepatocytes was 1.4 × 108 cells/body; the ammonia removal rate was more than 200 fmol/cell/hour (203.4 and 265.4 fmol/cell/hour with the first and second injections, respectively). The dose was judged to be sufficiently high to obtain therapeutic effectiveness according to our theoretical background.4 Because liver transplantation is approved as a treatment for end-stage hepatic failure, donor livers are preferentially allocated for organ transplantation and not for hepatocyte isolation. On rare occasions, the lack of appropriate donor-recipient matching (eg, infant donor livers) provides good-quality hepatocytes.2 Fetal livers are also considered to be an alternative cell source, although ethical issues remain to be resolved. At present, we have little choice but to use marginal donor tissues, such as livers obtained from donors after cardiac death and organs with steatosis, fibrosis, or a long ischemia time. However, there are unfavorable issues related to the use of marginal donors, including low viability and vulnerability to cryopreservation. In this respect, the remnant liver tissue of hyper-reduction procedures used in LDLT has the same quality as that of left lateral segment grafts. As for availability, there are 5 cases of hyper-reduction per year at our institution on average.5 The use of remnant liver tissues obtained from hyper-reduced LDLT procedures will, therefore, help to address the shortage of hepatocyte donors. Shin Enosawa, D.D.S., Ph.D. Reiko Horikawa, M.D., Ph.D. Akiko Yamamoto, M.D. Seisuke Sakamoto, M.D., Ph.D. Takanobu Shigeta, M.D. Shunsuke Nosaka, M.D., Ph.D. Junichiro Fujimoto, M.D., Ph.D. Atsuko Nakazawa, M.D., Ph.D. Akito Tanoue, M.D., Ph.D. Kazuaki Nakamura, Ph.D. Akihiro Umezawa, M.D., Ph.D. Yoichi Matsubara, M.D., Ph.D. Akira Matsui, M.D., Ph.D. Mureo Kasahara, M.D., Ph.D. National Center for Child Health and Development, Tokyo, Japan" @default.
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• W1493149511 date "2014-02-03" @default.
• W1493149511 modified "2023-10-18" @default.
• W1493149511 title "Hepatocyte transplantation using a living donor reduced graft in a baby with ornithine transcarbamylase deficiency: A novel source of hepatocytes" @default.
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• W1493149511 doi "https://doi.org/10.1002/lt.23800" @default.
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