Artificial cells in liver disease - Artificial Cells, Cell Engineering and Therapy - page 226

9.4 Clinical experience with hepatocyte

transplantation

A tremendous number of controlled animal experimentations over the past three
decades have enabled the implementation of the first of several of hepatocyte
transplantation trials in humans. The early hepatocyte transplantation trials in
humans were uncontrolled and resulted in a variable outcome. The patient
population was also varied and did not facilitate good comparison among the
various clinical studies that were conducted worldwide. Furthermore, the
etiology of patients studied ranged from end stage liver cirrhosis to those with
fulminant hepatic failure and congenital metabolic liver disease. The number of
hepatocytes transplanted also differed significantly, as did the source of hepato-
cytes and site of transplantation. Nevertheless, the results were encouraging and
have prompted other more carefully designed trials that have all, on the whole,
validated the promises of the earlier experimental observations in animals.
The first clinical trials of hepatocyte transplantation were reported by Mito
and Kusano, who injected isolated human hepatocytes into the spleen of 10
Japanese patients with liver cirrhosis or chronic hepatitis. 27 Although some
transient improvement was observed initially, no obvious clinical improvement
was observed in the patients studied. However, a year later in 1994, investigators
in India conducted a study in which seven patients with fulminant hepatic failure
of different etiologies were intraperitoneally transplanted with approximately 60
million hepatocytes isolated from aborted fetuses. 28 In this trial, fetal hepato-
cytes were pooled from fetuses ranging in gestational ages ranging from 26 to 34
weeks. Unmatched control patients did not receive hepatocyte transplantation
and consisted of those patients who did not consent to the procedure.
Investigators found a significant difference in the survival of patients treated
with hepatocyte transplantation (48%) compared with matched controls (33%).
In those patients that survived a decrease in blood ammonia and bilirubin levels
was observed. No beneficial effects were seen with regard to prothrombin times.
Investigators observed 100% survival in patients treated during early stages
(Grade III) of hepatic encephalopathy as compared to those in late stages (Grade
IV) who all died. The investigators of this study concluded that fetal hepatocyte
transplantation had a beneficial effect on the patient's outcome when hepatocyte
transplantation was used early in the clinical course of the disease.
In the United States approximately 19 acute liver failure patients have been
treated with hepatocyte transplantation, primarily as a bridge to trans-
plantation. 29,30 Patients were infused with approximately 10 million to 10
trillion allogeneic hepatocytes obtained from cadaveric livers. Hepatocytes were
infused either into the splenic artery or portal vein. In some cases, hepatocytes
were infused into the portal vein via transjugular catherization. As was expected
from the nature of these experimental clinical trials and small patient population
the results were largely inconclusive. Although functionally viable hepatocytes