Selective plasma filtration for treatment of fulminant hepatic failure induced by D-galactosamine in a pig model.
BACKGROUND
Plasma exchange may be useful for treating patients with fulminant hepatic failure but during the procedure growth factors that are important for hepatic regeneration are discarded. Addition of a selective plasma filter to the plasmapheresis circuit could eliminate protein bound toxic substances and retain growth factors for hepatic regeneration. This process is called selective plasma filtration.


OBJECTIVE
To determine if selective plasma filtration could be a useful treatment modality for fulminant hepatic failure.


METHODS
The system was tested in five groups of pigs with fulminant hepatic failure induced by galactosamine: group I, diseased control group (n=5); group II, sham control, (n=6); group III, plasma exchange (n=6); group IV, treatment with AC-1770 selective plasma filter (n=7); and group V, treatment with AC-1730 selective plasma filter which had a smaller pore size than AC-1770 (n=7). Fresh pig plasma was given to replace filtered plasma in pigs of groups III, IV, and V. Treatment was initiated 48 hours after administration of 0.75 g/kg galactosamine. The efficacy of selective plasma filtration was assessed by survival rate and improvement in haematological, biochemical, and immunohistological parameters.


RESULTS
Pigs treated with AC-1770 or AC-1730 selective plasma filters survived longer than the other groups (group I: 55 (10) hours; group II: 68 (7) hours; group III: 91 (10) hours; group IV: 269 (156) hours; group V: 950 (555) hours). One pig in group IV survived for 50 days; one pig in group V survived for 77 days and another pig in group V is still alive (>150 days). After treatment, plasma levels of aspartate aminotransferase, bilirubin, bile acid, ammonia, lactate dehydrogenase, and alpha-glutathione-S-transferase decreased. Substantial amounts of tumour necrosis factor alpha (TNF-alpha) and endotoxin were found in the filtrate. The selective plasma filtration groups retained significantly higher amounts of hepatocyte growth factor than plasma exchange alone. Similar TNF-alpha clearance was observed in the selective plasma filtration groups and the plasma exchange group. On day 4, significant improvement in liver function, as measured by the indocyanine green clearance test, was observed in groups IV and V but not in the other groups. A higher regeneration index of hepatocytes was also observed in the groups treated with AC-1770 and AC-1730 selective plasma filters.


CONCLUSIONS
Selective plasma filtration improved survival time and expedited liver regeneration in pigs with fulminant hepatic failure.
Ho
D W Y
DW
Centre for the Study of Liver Disease and Department of Surgery, University of Hong Kong, Hong Kong.
Fan
S T
ST
To
J
J
Woo
Y H
YH
Zhang
Z
Z
Lau
C
C
Wong
J
J
D000818:Animals; D001663:Bilirubin / Q000097:blood; D005260:Female; D005374:Filtration / Q000379:methods; D005688:Galactosamine / Q000009:adverse effects*; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D017093:Liver Failure / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D010951:Plasma Exchange / Q000379:methods*; D010956:Plasmapheresis / Q000379:methods; D016019:Survival Analysis; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha; D017228:Hepatocyte Growth Factor; D005688:Galactosamine; D001663:Bilirubin