Hepatocellular transplantation in acute liver failure

Acute liver failure carries a high rate of mortality, but if metabolic support can be maintained for a critical period, liver healing and recovery are possible. Current techniques of temporary hepatic support are cumbersome and inconsistently effective. A study was made on the ability of dispersed hepatocytes to provide metabolic support when transplanted to rats with liver failure induced by dimethylnitrosamine (DMNA). DMNA was administered i.v. (20 mg/kg) to 92 Lewis rats. Animals were divided into 4 groups receiving different treatments 24 hr after DMNA administration. Group 1: i.p. transplantation of hepatocytes prepared from 2.0 gm of normal isologous rat liver; group 2: infusion into the portal vein of hepatocytes prepared from 1.5 g of liver; group 3: infusion of saline into the portal vein; group 4: no further treatment. The percentages surviving in each group 3 wk after DMNA administration were 63%, 71%, 17%, and 6%, respectively. Mean serum glutamic oxaloacetic transaminase (SGOT) levels 3 days after DMNA administration were similar in the 4 groups, indicating that the degree of liver damage was equivalent. A significantly higher proportion of hepatocyte treated rats survived. Liver histology after DMNA administration showed hemorrhagic central lobular necrosis. A return to near-normal architecture occurred by 3 wk in surviving animals. In group 2 hepatocytes were seen in portal venules, sinusoids, and central veins. It is concluded that dispersed hepatocytes, transplanted either i.p. or via the portal vein, can provide sufficient metabolic support to allow for recovery from drug-induced hepatic necrosis.