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12.10.2017 | Original Article | Ausgabe 1/2018

Journal of Inherited Metabolic Disease 1/2018

Human heterologous liver cells transiently improve hyperammonemia and ureagenesis in individuals with severe urea cycle disorders

Zeitschrift:
Journal of Inherited Metabolic Disease > Ausgabe 1/2018
Autoren:
Jochen Meyburg, Thomas Opladen, Ute Spiekerkötter, Andrea Schlune, Jens-Peter Schenk, Jan Schmidt, Jürgen Weitz, Jürgen Okun, Friederike Bürger, Tawfeg Ben Omran, Ghassan Abdoh, Hilal Al Rifai, Ahmad Monavari, Vassiliki Konstantopoulou, Stefan Kölker, Marc Yudkoff, Georg F. Hoffmann
Wichtige Hinweise
Communicated by: Bridget Wilcken

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s10545-017-0097-4) contains supplementary material, which is available to authorized users.
Jochen Meyburg and Thomas Opladen contributed equally to this work.

Abstract

Background

Urea cycle disorders (UCDs) still have a poor prognosis despite several therapeutic advancements. As liver transplantation can provide a cure, liver cell therapy (LCT) might be a new therapeutic option in these patients.

Methods

Twelve patients with severe UCDs were included in this prospective clinical trial. Patients received up to six infusions of cryopreserved human heterologous liver cells via a surgically placed catheter in the portal vein. Portal vein pressure, portal vein flow, and vital signs were monitored continuously. Calcineurin inhibitors and steroids were used for immunosuppression. In four patients, ureagenesis was determined with stable isotopes. Number and severity of hyperammonemic events and side effects of immunosuppression were analyzed during an observation period of up to 2 years.

Results

No study-related mortality was observed. The application catheter dislocated in two children. No significant side effects of catheter application or cell infusion were noted in the other ten patients. The overall incidence of infections did not differ significantly from a historical control group, and no specific side effects of immunosuppression were found. Seven patients were treated per protocol and could be analyzed for efficacy. Severe metabolic crises could be prevented in all of these patients, moderate crises in four of seven. Ureagenesis increased after cell infusion in all patients investigated.

Conclusions

We found a favorable safety profile with respect to catheter placement, intraportal liver cell infusion, and immunosuppression. More than half of the children treated per protocol experienced metabolic stabilization and could be safely bridged to liver transplantation.

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Zusatzmaterial
ESM 1 Primary and secondary endpoints of the study (DOCX 76.1 kb)
10545_2017_97_MOESM1_ESM.docx
ESM 2 Inclusion and exclusion criteria (DOCX 92.0 kb)
10545_2017_97_MOESM2_ESM.docx
Literatur
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