UCL
Université
Catholique
de
Louvain
Hepatocyte preservation for treatment
of inborn error of liver metabolism
and fulminant hepatitis
Senior scientists : Etienne SOKAL
sokal@pedi.ucl.ac.be
Tel (32) 2 764 52 85 / 13
87
Mustapha NAJIMI
STAFF
KEY WORDS FOR R&D
Etienne SOKAL
Mustapha NAJIMI
Xavier STEPHENNE
Celine CALLIAU
Liver transplantation
Cell therapy
Tissue engineering
Cryopreservation
Inborn error of metabolism
RESEARCH FIELD AND SUBJECTS
The laboratory of Pediatric Hepatology and Cell Therapy is closely linked to the
Pediatric Liver Unit and Pediatric Liver Transplant programme of the "Université
Catholique de Louvain" – Cliniques St Luc.
Research is mainly dedicated to solve the clinical problems and to improve results,
quality of life and survival of pediatric patients with chronic liver diseases, inborn
errors of metabolism and liver transplantation. Mechanisms of diseases are
investigated. The main field of research includes liver cell transplantation including
also cell and tissue cryopreservation. Our clinical target for cell therapy includes
inborn errors of liver metabolism i.e. mitochondrial respiratory chain disorders, urea
cycle disorders, intra-hepatic cholestasis and miscellaneous inborn errors of liver
metabolism. Research is also targeted on immunosuppression and related
disorders, in particular post transplant lym-phoproliferative diseases associated to
Epstein-Barr virus infection. This includes cell culture and immunology research. We
also have a specialised investigation center for pediatric pharmacologic research,
following GCP rules.
PRODUCTS AND SERVICES
Hepatocyte isolation in animal and human subjects is mainly performed to isolate the
hepatocytes according to good manufactory practices. These hepatocytes are aimed
to be used for intra-portal transfusion to correct inborn errors of liver metabolism.
Many of these diseases are due to a single enzyme defect which may cause severe
damage to distant organs such as the brain, the kidney or any other organ.
Isolated and cryopreserved hepatocytes can be transfused in the portal vein and integrated into the parenchyma of the native liver.
A small percentage of hepatocytes may be sufficient to bring a sufficient amount of
enzyme activity to correct the inborn meta-bolic disease. This may avoid orthotopic
liver transplantation and the risks related to this radical procedure. In fulminant
hepati-tis, hepatocytes may be transfused in the portal vein and allow the liver to
maintain a sufficient function until recovery of the na-tive liver of the patient.
Experiments are performed to improve quality of fresh and cryopreserved cells by
understanding mechanisms of cell death (apoptosis) related or not to mitochondria.
MAIN EQUIPMENT
We have at our disposal all facilities to perfuse animal and human livers, isolate
cells, and cryopreserve the cells.
We have own GMP facility for human cell isolation. We have also access to tissue
bank and cryopreservation equipment, cell culture, immunology, immunohistochemistry.
REPRESENTATIVE REFERENCES
SOKAL EM, TRIVEDI P, PORTMANN B, MOWAT AP. Adaptive changes of metabolic zonation during
the development of cirrhosis in growing rats. Gastroen-terology, 1990;99:785-792.
SOKAL EM, VEYCKEMANS F, DE VILLE DE GOYET J, MOULIN D, VAN HOOREBEECK N,
ALBERTI D et al. Liver transplantation in children less than one year of age. J Pediatr, 1990;117:205210.
SOKAL EM, MOSTIN J, BUTS JP. Liver metabolic zona-tion in rat biliary cirrhosis: distribution is
reverse to that in toxic cirrhosis. Hepatology, 1992;15:904-908.
SOKAL EM, BUSTOS R, VAN HOOF F, OTTE JB. Liver transplantation for hereditary tyrosinemia.
Early transplantation following patient's stabilization. Transplantation, 1993;54:937-939.
SOKAL EM. Adaptive changes of metabolic zonation in liver cirrhosis. (Brussels: thèse d'agrégation,
Univer-sité Catholique de Louvain) 1993.
SOKAL EM, BAUDOUX MC, COLLETTE E, HAUS-LEITHNER V, LAMBOTTE L, BUTS JP. Branched
chain amino acids improve body composition and nitrogen balance in a rat model of extra-hepatic
biliary atresia. Pediatr Res, 1996;40:1:66-71.
STEPHENNE X, NAJIMI M , SMETS F, REDING R, DE VILLE DE GOYET J, SOKAL EM.
Cryopreserved Liver Cell Transplantation controls Ornithine Transcarbamylase deficient patient while
waiting Liver Transplantation. American Journal of transplantation. In press.
STRAUTNIEKS SS, BULL L, KNISELY AS, KOCOSHIS SA, DAHL N, ARNELL H et al. A gene
encoding a liver specific ABC transporter is mutated in a progressive familial intrahepatic cholestasis.
Nature Genetics, 1998;20:233-238.
M. M. Jonas, D. A. Kelly, J. Mizerski, I. B. Badia, J. A. Areias, K. B. Schwarz, N. R. Little, M. J.
Greensmith, S. D. Gardner, M. S. Bell, and E. M. Sokal. Clinical trial of lamivudine in children with
chronic hepatitis B. N.Engl.J.Med. 346 (22):1706-1713, 2002.
0 E. M. Sokal, H. S. Conjeevaram, E. A. Roberts, F. Alvarez, E. M. Bern, P. Goyens, P. Rosenthal, A.
Lachaux, M. Shelton, J. Sarles, and J. Hoofnagle. Interferon alfa therapy for chronic hepatitis B in
children: a multinational randomized controlled trial. Gastroenterology 114 (5):988-995, 1998.
0 E. M. Sokal, M. Melchior, C. Cornu, A. T. Vandenbroucke, J. P. Buts, B. J. Cohen, and G.
Burtonboy. Acute parvovirus B19 infection associated with fulminant hepatitis of favourable
prognosis in young children. Lancet 352 (9142):1739-1741, 1998.
0 E. M. Sokal, E. A. Roberts, G. Mieli-Vergani, P. McPhillips, M. Johnson, J. Barber, N. Dallow, E.
Boxall, and D. Kelly. A dose ranging study of the pharmacokinetics, safety, and preliminary efficacy
of lamivudine in children and adolescents with chronic hepatitis B. Antimicrob.Agents Chemother. 44
(3):590-597, 2000.
0 E. M. Sokal, F. Smets, A. Bourgois, L. Van Maldergem, J. P. Buts, R. Reding, Otte J. Bernard, V.
Evrard, D. Latinne, M. F. Vincent, A. Moser, and H. E. Soriano. Hepatocyte transplantation in a 4year-old girl with peroxisomal biogenesis disease: technique, safety, and metabolic follow-up.
Transplantation 76 (4):735-738, 2003.
0 I. Scheers, V. Bachy, X. Stephenne, and E. M. Sokal. Risk of hepatocellular carcinoma in liver
mitochondrial respiratory chain disorders. J.Pediatr. 146 (3):414-417, 2005.
0 M. Najimi and E. Sokal. Update on liver cell transplantation. J.Pediatr.Gastroenterol.Nutr. 39
(4):311-319, 2004.