HEPATIC REGENERATION IN FULMINANT HEPATIC-FAILURE

Survival in patients with fulminant hepatic failure (FHF) depends on whether regenerative activity is prompt enough and of sufficient magnitude to restore hepatic function to necessary levels prior to the development of life threatening complications. Unfortunately, in the setting of FHF, the liver's ability to regenerate is impaired, both in terms of the rapidity of its onset and magnitude. The reason(s) for this impairment remain unclear and are the subject of extensive investigations. Data from studies in experimental animals and early reports in humans with acute liver failure suggest that there is no deficiency and, in fact, there is an excess of many hepatic growth promoters. Thus, either an intrinsic defect exists in the remnant liver's ability to respond to these growth promoters or growth inhibitors are present to an even greater extent. The results of previous cross-circulation experiments and documentation of extremely high concentrations of newly identified growth inhibitors suggest that the latter are more likely to be operative. As a result, therapeutic endeavours are targeted at lowering the levels of various growth inhibitors. An exciting new approach - based on the realization that many of these growth inhibitors act through a common final pathway - has been to exogenously administer the product of this pathway in an attempt to optimize regenerative activity in FHF.