Selective plasma filtration for treatment of fulminant hepatic failure induced by D-galactosamine in a pig model

Abstract

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. Aims: 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 α-glutathione-S-transferase decreased. Substantial amounts of tumour necrosis factor α (TNF-α) 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-α 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. Conclusion: Selective plasma filtration improved survival time and expedited liver regeneration in pigs with fulminant hepatic failure.

Adenoviral Gene Transfer of Hepatic Stimulator Substance Confers Resistance Against Hepatic Ischemia–Reperfusion Injury by Improving Mitochondrial Function

“…Many studies have revealed that HSS protects the liver from injuries caused by various types of toxins, such as carbon tetrachloride (Mei et al, 1993), d-galactosamine (Ho et al, 2002), ethanol (Liatsos et al, 2003), and H 2 O 2 (Wu et al, 2007). Consistently, inhibition of intracellular HSS expression by an antisense approach reduces cell survival against free radical insults, suggesting that HSS might be a cell survival factor (Thirunavukkarasu et al, 2008).…”

Combined human growth hormone and lactulose for prevention and treatment of multiple organ dysfunction in patients with severe chronic hepatitis B

“…It was reported that the mortality rate of severe hepatitis was more than 80% if liver transplantation was not performed [4] . Liver transplantation is the optimal choice for treatment of liver failure.…”

“…Liver transplantation is the optimal choice for treatment of liver failure. Therefore, the fundamental purpose of internal medical treatment is to make the state of illness stable and to wait for appropriate liver donor for liver transplantation [4] . Many complications in severe hepatitis patients had a close relation to the prognosis [1,2] .…”

Effects of hemoperfusion adsorption and/or plasma exchange in treatment of severe viral hepatitis: A comparative study

“…In the fresh frozen plasma for exchange, there are a great deal of citrates which can increase the incidence of side effects after infused into the body and can do harm to hepatocyte energy metabolism and hepatocyte regeneration. How to advance various therapies and combine them with bioartificial liver support system in order to get good effects and reduce the side effects await further study [36][37][38][39][40][41] .…”