Artificial liver support devices for fulminant liver failure.

Fulminant hepatic failure is a clinical syndrome defined by acute liver injury leading to hepatic encephalopathy within 8 weeks of the onset of jaundice. Even though the acute injury may be inflicted by various causes, the clinical picture is dominated by diverse metabolic derangements resulting from the loss of the liver's synthetic and detoxifying function. This loss of liver function causes a coagulopathy, hemodynamic instability, encephalopathy with cerebral edema, and increased susceptibility to infection and often culminates in multiorgan failure. 10 Despite maximal medical therapy, the mortality rate in these patients is high. The only successful treatment for fulminant hepatic failure, when poor prognostic signs are present, is an emergent orthotopic liver transplantation. 94 The experience with orthotopic liver transplantation for fulminant hepatic failure have documented 2- and 5-year patient survival rates of 92% 8 and 60%, 36 respectively. Unfortunately, although patients with fulminant hepatic failure receive the highest priority for transplantation, the shortage of suitable organs often means that a liver will not be available soon enough to prevent death. Therefore, other treatment modalities are needed to support the patient with fulminant hepatic failure until a suitable liver allograft is obtained for transplantation or the patient's own liver regenerates sufficiently to resume normal function. 15,49 The two leading causes of death from fulminant hepatic failure are cerebral edema leading to herniation with brain death and overwhelming sepsis. The medical management of cerebral edema is limited. Thus any artificial liver-support device must primarily be able to treat medically refractory elevations in intracranial pressure. 16 A secondary effect of the artificial liver-support device may include the enhancement of liver regeneration. 124 With fulminant hepatic failure the regeneration of the liver is inhibited. In vitro studies have shown that this inhibition of liver regeneration is most likely caused by substances contained within the serum of patients with fulminant hepatic failure. 4,5,57,58,63,110 Because of the complexity of liver regeneration, it is unclear whether this inhibition of liver regeneration is caused by a deficiency of promoting substances or by the presence of inhibiting substances. 43,44,59,82,85,132 Attempts to develop an artificial liver started in the 1950s. 70,72,76,91,109 These early artificial liver-support devices attempted to restore the homeostasis of patients with acute liver failure in a way analogous to hemodialysis in patients with acute renal failure. Today both mechanical devices and hybrid biologic-mechanical devices are used for artificial liver support.* *References 6,14,23,60,62,64,66,92,103,123,130 The poor understanding of the pathogenesis of liver failure has led to difficulty in evaluating the efficacy of these devices. Fortunately, the recent widespread application of these newer artifical-liver technologies has finally allowed randomized trials to evaluate their merit. This article discusses the various techniques that have been used in the past for patients with fulminant hepatic failure and gives an overview of the current technologies and possible future approaches in treating fulminant hepatic failure with an artificial liver-support device.