Current support or replacement therapies for fulminant acute hepatic failure are frequently very disappointing. In this study, human hepatic stimulator substancea liver-specific growth factorwas partially purified h m human fetal liver cells and characterized by its biological effects. Almost 70-fold protein content was purified with an approximately 80-fold increase in specific growth stimulator activity. Human hepatic stimulator substance proved to be heatstable, protase-sensitive, organ-specific and speciesnonspecific. Human hepatic stimulator substance produced a two-to threefold increase of 'H-thymidine incorporation into hepatic DNA when iqjected intraperitoneally into growing weanling mice (nonhepatectomized) or regenerating rats (34% hepatectomy). The effects of hHSS in reversing the lethality of D-galactosarmn e (1.6 gm/kg body weight)-induced heqatic necrosis in rats were further evaluated. A survlval rate of 4% (n = 24). 41% (n = 12, p < 0.05), 33% (n = 12, p < 0.06), 31% (n = 13, p < 0.06) and 18% (n = 11, p > 0.06) was observed when the rats were injected with 4 ml of saline intraperitoneally, 4 ml of human intact fetal hepatocytes (2.4 x 10') intraperitoneally, 4 ml of human hepatic stimulator substance intraperitoneally, 2 ml of twofold concentrated human hepatic stimulator substance intravenously and 1 ml of fourfold human hepatic stimulator substance intramuscularly, respectively, 20 hr after poisoning. These results suggwted that human hepatic stimulator substance could succeesfully improve survival in rats with chemically induced acute liver failure by hepatocyte proliferation and might represent a significant potential for the management of clinical fulminant hepatic failure (HEPATOLOGY 199012:1144-1161.)
A major objective of clinical hepatology is the development of a successful method for the treatment of fulminant acute hepatic failure, a disease that has an extremely poor prognosis and carries a high mortality at present. Numerous reports in the past years have