Biomedical Engineering Reference
In-Depth Information
serum alanine transaminase, and aspartate transaminase. The Child-Pugh score
improved in 7 out of 9 patients and in 5 patients ascites production had declined.
Two studies so far aimed to ameliorate acute on chronic liver disease by
administration of granulocyte—colony stimulating factor (G-CSF) treatment. In
contrast to an earlier study by Campli et al. [
119
] a more recent study from India
showed profound effects on short-term survival, which was associated with a
marked increase of CD34 stem cells in the liver of recipients [
120
].
10.5.3 Hereditary Liver Disease
Liver organ transplantation can be viewed as a form of gene therapy for inherited
liver diseases since the procedure substitutes a defective gene with a normal copy
from a healthy donor. Animal studies have shown that for most monogenetic liver
diseases partial substitution of a missing or defective protein is able to reverse the
clinical phenotype and can result in complete remission of the disease. This
redundancy opens the possibility to apply minimally invasive therapies such as cell
and gene therapies to correct an existing gene defect. Although many hurdles still
exist, feasibility has been proven unequivocally in animal models and therapeutic
protocols are now emerging in the clinical arena.
10.5.3.1 Transplantation of Mature (Adult) Hepatocytes
In recent years the interest in liver cell therapy has been increasing continuously,
since the demand for whole liver transplantations in human beings far outweighs
the supply [
121
]. From the clinical point of view, transplantation of hepatocytes or
hepatocyte-like cells may represent an alternative to orthotopic liver transplants
for the correction of genetic disorders resulting in metabolically deficient states.
The aim of hepatocyte transplantation in metabolic disease is to partially replace
the missing function without the need to replace the whole organ. Almost 30
children and adults who received liver cell therapy for metabolic liver disease are
reported in literature [
122
,
123
]. Clinical therapies up to now have been performed
by infusing fresh or cryopreserved primary hepatocyte suspensions isolated from
donated organs. The availability of high quality liver tissue for cell isolation,
however, has slowed the widespread application of this therapy. Furthermore, the
clinical situation of target patients is rarely immediately life threatening and often
acceptable conventional therapies are available. Therefore, the potential benefit
must be carefully weighed against any possible complications, such as side effect
from immunosuppression, hepatocyte embolization of the pulmonary vascular
system, sepsis or hemodynamic instability.
Objective parameters such as laboratory data (i.e. bile acid, clotting factors,
etc.) can be determined to unequivocally assess the efficacy of the treatment. The
results of hepatocyte transplantation for many metabolic liver diseases have been
