Animal Models of Hepatic Failure and Hepatic Encephalopathy

Abstract

Acute fulminant hepatic failure (FHF) in man is a clinical syndrome that occurs as a result of a sudden and severe impairment of liver function. This may in some cases be associated with massive necrosis of liver cells; in other circumstances, metabolic abnormalities, often accompanied morphologically by microvesicular steatosis, result in a similar syndrome despite the absence of significant necrosis. Except when the syndrome evolves during the course of a prolonged bout of viral hepatitis, preceding liver disease is absent in these patients. Although the short-term prognosis in FHF is much worse than for chronic liver failure, the hepatic lesion is potentially reversible. Also reversible is acute hepatic encephalopathy, a neuropsychiatric syndrome, that is frequently associated with fulminant hepatitis. It is not known with any certainty whether coma in acute hepatic failure results from the accumulation of toxic metabolites or a deficiency of substances produced by the liver and essential for normal brain function. In part for this reason, attempts to develop an artificial liver device for the treatment of acute hepatic failure and encephalopathy — analogous to the artificial kidney — have thus far been unsuccessful.