Immunomonitoring after paediatric liver transplantation – in search for markers of over- or under-immunosuppression

A multi-centre, open, prospective observational trial in children with steroid free immuno suppression following paediatric liver transplantation -The ChilSFree Trial- 

Principle Investigator:

Prof. Dr. med. U. Baumann

Paediatric Gastroenterology and Hepatology, 
Dept. of Paediatric Liver, Kidney and Metabolic Diseases. 
Hannover Medical School
Carl-Neuberg-Strasse 1, 30625 Hannover, Germany
Email: baumann.u@remove-this.mh-hannover.de
Phone: -49 - 511 532 3233
Fax: -49 – 511 532 3294


Collaborating Centres : 
Florence Lacaille, MD and  Dominique Debray, MD
Pédiatre hépatologue
Service d'Hépatologie-Gastroentérologie-Nutrition
Hôpital Necker-Enfants malades
149 rue de Sèvres
75015 Paris, France
phone: (33) 01 44 49 44 12 (secretary), (33) 01 44 49 42 28 (direct line)
Fax : (33) 01 44 49 25 01
Email: florence.lacaille@nck.aphp.fr
Dominique.debray@nck.aphp.fr

Lorenzo D'Antiga, MD, FEBS
Medical Director
Paediatric Liver, GI and Transplantation
Ospedali Riuniti di Bergamo
Largo Barozzi 1
24128 Bergamo - Italy
pone: ++39035269294
Fax: ++39035266581
Email: ldantiga@remove-this.ospedaliriuniti.bergamo.it

Valérie McLin, MD
Dpt Pédiatrie, Serv. spécialités pédiatriques
Rue Gabrielle-Perret-Gentil 4
1211 Geneva 4, Switzerland
Email : Valerie.McLin@hcuge.ch
phone: +41 22 372 46 72

Loreto Hierro, MD
Servicio de Hepatología y Transplante
Hospital Infantil Universitario La Paz Madrid
Paseo de la Castellana 261
28046 Madrid- Spain
Tel : 0034917277065
Fax: 0034917277543
Email: lhierro.hulp@salud.madrid.org
 
Patrick McKiernan, MD
Liver Unit
Birmingham Childrens Hospital
Steelhouse Lane
Birmingham B4 6NH, UK
Tel: 0121 333 8253/8263
Fax:0121 333 8251
Email: Deirdre.kelly@bch.nhs.ukPAT.MCKIERNAN@bch.nhs.uk

Joanna Pawlowska, MD
Centrum Zdrowia Dziecka
Warszawa, Poland
Al. Dzieci Polskich 20
04-730 Warszawa - Poland
Phone: -48 22 815 70 00
Email: p.socha@remove-this.czd.pl

 

Abstract

Improved results in paediatric liver transplantation have gradually shifted focus of clinical research from increasing patient survival to enhancement of long-term quality of life. One of the major challenges today is to optimise immunosuppression post transplantation in order to reduce drug toxicity and infection, whilst maintaining adequate immunosuppression to prevent rejection and graft loss. One of the difficulties in achieving this goal lies in understanding the functional level of therapeutic immunosuppression. Neither total drug exposure nor trough levels of immunosuppressive medication sufficiently reflect the pharmaceutical effects on the immune system due to a considerable inter-subject variability in the sensitivity to suppression of immune function. 

Our study is a prospective, open, non-randomized observational multicentre trial and aims at characterising the changes in the immune system induced by immunosuppressive therapy after liver transplantation. We propose a prospective multicentre study in children who undergo liver transplantation. These children will receive extensive immune monitoring using a broad panel of immune markers over the course of 12 months. Development of immune monitoring data will be compared with the clinical course, notably the occurrence of infections and rejection. The ultimate scientific aim is to define markers of immune functioning that are specific to the functional degree of immunosuppression after liver transplantation, and which will eventually allow tailor-made, individualized dosing of immunosuppression for each patient.

The study implies the collaboration of different European liver transplant centres, in Germany (principal investigator), in France, in Switzerland, in Italy, in Spain, in the United Kingdom and in Poland. This will increase the scientific gain of the study by increasing patient numbers. At the same time, structures for future collaborations will be established. A database for research purposes will be created as a new common platform for European cooperation. This will help to develop and implement common therapeutic guidelines in the field of paediatric hepatology, for the benefit of future patient care.