Hepatic regeneration: implications in fulminant hepatic failure.

Although the incidence of fulminant hepatic failure appears to have decreased worldwide, the management of this dreaded condition remains unsatisfactory (1). Despite ingenious methods of treatment, the mortality in patients with grade IV coma is still between 80 and 90% in most major series (15, 20). Furthermore the mortality is nearly 100% in patients ov~r the age of 45 who develop grade IV coma (7). Saunders et al have pointed out that although heroic measures, such as exchange transfusion, cross circulation and isolated liver perfusion, can reverse the neurologic and, to an extent, the hematologic complications of massive liver cell necrosis in some patients, none have increased the survival rate (1 5). The same unfortunately also applies to newer methods of treatment (1). The hope that an «artificial liver» could be developed to replace the many intricate functions of the liver, while waiting for regeneration to take place, has not been borne out in practice because of the complexity of the liver itself (2, 7). and because of the surprising finding that many of these patients do not regenerate their livers adequately, if at all (10, 15). In the Cape Town Experience of 119 cases of fulminant hepatic failure, 68 patients were in grade IV coma. In this group the survival rate was only 16% despite intensive care and the use of various additional treatment modalities (15, 20). Autopsies were available in 40 patients. In 23 some regeneration was noted but in only 5 was this of significant degree. In 7 no regeneration was detected at all. Event patients who died late after the onset of the illness frequently showed little evidence of regeneration (15). This led them to conclude in 1972 that -although the liver has an enormous regenerative capacity in certain experimental situations, and sometimes after massive necrosis, this ability has been overemphasized in fulminant hepatitis and is not consistent with our experience in many patients. All the current methods of treatment ...... will not influence mortality unless sufficient regeneration occurs spontaneously or can be stimulated therapeutically» (15). This lack of regeneration in many patients with severe fulminant hepatic failure has been confirmed in other large series (10, 23). The conclusion of a recent conference held at the NIH was that the best one can offer a patient with fulminant hepatic failure at this time is meticulous intensive care (1, 2). If artificial liver support systems are inadequate, and lack of regeneration a problem, can anything be done to potentiate or stimulate regeneration in patients with fulminant hepatic failure? At this time the answer is no, largely because of our limited knowledge of what switches on or controls liver regeneration. In this editorial the authors will address themselves to what is currently known about the control of liver regeneration and speculate how this knowledge might be used in the future management of patients with fulminant hepatic failure.