Acute liver failure: Where are the challenges?

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Acute liver failure (ALF) classically defined as the onset of encephalopathy within 8 weeks of the appearance of jaundice, remains one of the most challenging medical emergencies. While, mostly depending on the aetiology, a number of patients fully recover with the best supportive care; the prognosis has dramatically changed only with the advent of orthotopic liver transplantation (OLT). Thus, the main issues must focus on the identification of those patients who may recover without OLT, on the prevention of irreversible patient deterioration until an organ becomes available, the best timing for listing for OLT, and the types of organ for transplantation such as a whole cadaveric vs. a partial cadaveric or living donor grafts.

In this eighth forum of the series Forum on Liver Transplantation, we will discuss the current challenges associated with ALF. In the 1st article E. Renner reviews the various criteria allowing the most appropriate timing for listing a patient with ALF for transplantation. Dr. Renner favours the King’s College criteria, although other parameters such as factor V and lactate levels should also be considered. Patients with subacute forms of liver failure pose particular problems, and the clinical experience of the care givers may be paramount in improving survival in those patients. A focus of several groups has been in developing strategies to enable safe bridging to transplant or spontaneous recovery. In an excellent overview A. Singhal and J. Neuberger present current and innovative bridging options including hepatocyte transplantation, and a variety of bioartificial and artificial devices. While effective in improving a number of parameters, none of these strategies has yet convincingly demonstrated improved survival in patients with ALF. The most practical, cost effective and promising devices are artificial devices such as the MARS or Prometheus systems.

Brain Oedema remains one of the most challenging and common causes of death in patients with ALF. In a superb article, A. Blei summarizes the complex pathogenesis of brain oedema in this population, and on this basis discusses preventive and therapeutic modalities. Well balanced “pro and con” arguments are presented regarding the use of intracranial pressure monitoring or osmotic agents. Probably, a largely underused strategy is mild hypothermia with drop in body temperature to 32–34°C, which effectively reduces intracranial pressure and other toxic metabolic activities associated with poor outcome.

Finally, a debate exists among transplant surgeons regarding the most suitable type of grafts to consider in patients with ALF. Of course, this choice depends on the local availability of cadaveric grafts, as the timing of transplantation in this population, more than with any other indications, is the single most important factor determining survival. D. Jaeck, P. Pessaux, and Ph. Wolf make the case of auxillary liver transplantation. They argue in favour of auxillary orthotopic liver transplantation (called APOLT) using a right cadaveric hemiliver. The advantages are the possibility for the native liver to regenerate once the toxic cause of ALF has resolved allowing to discontinue all immunosuppressive drugs. S.G. Lee, C.S. Ahn, and K.H. Kim rather argue in favour of living donation. Results are encouraging, and living donation is the only available option in Korea and many other countries in Asia. Finally, T.M. Mark and R.S. Chari insist that the gold standard must remain whole cadaveric OLT, and other options should be considered only in clinical trials or centres without or very low access to cadaveric organs.

I believe that this Forum will be helpful to both experienced hepatologists and transplant surgeons, as well as all others dealing with this heterogeneous and difficult group of patients covered under the term “ALF”. These cases are currently rare and even in reasonably large transplant programs; many may be exposed only to a few cases. Thus, knowledge of the current challenges and controversies in this population may be of great value.