Fulminant hepatic failure (FHF), defined by the presence of hepatic encephalopathy as the consequence of severe liver injury and originally described as occurring within 8 weeks of the onset of symptoms in patients without pre-existing liver disease,<sup>107 Trey C., Davidson C.S. The management of fulminant hepatic failure Progress in Liver Failure New York: Grune and Stratton (1970).  282-298

Cliquez ici pour aller à la section Références</sup> is a potentially devastating syndrome which may include as components hemodynamic instability, cerebral edema, renal failure, coagulopathy, profound metabolic disturbances, and susceptibility to infection. Because the jaundice-to-encephalopathy time is an important index,<sup>6 Bernuau J., Rueff B., Benhamou J.P. Fulminant and subfulminant liver failure: Definitions and causes Semin Liver Dis 1986 ;  6 : 97-106  [cross-ref]

Cliquez ici pour aller à la section Références, 74 O'Grady J.G., Schalm S., Williams R. Acute liver failure: Redefining the syndromes Lancet 1993 ;  342 : 373-375

Cliquez ici pour aller à la section Références, 76 O'Grady J.G., Alexander G.J.M., Hayllar K.M. , et al. Early indicators of prognosis in fulminant hepatic failure Gastroenterology 1989 ;  97 : 439-445

Cliquez ici pour aller à la section Références</sup> other terminologies have been proposed that are related to this interval rather than often nonspecific symptoms. Bernuau et al<sup>6 Bernuau J., Rueff B., Benhamou J.P. Fulminant and subfulminant liver failure: Definitions and causes Semin Liver Dis 1986 ;  6 : 97-106  [cross-ref]

Cliquez ici pour aller à la section Références</sup> use the term FHF to describe the onset of encephalopathy within 2 weeks of the onset of jaundice and use the term subfulminant hepatic failure to describe cases with a jaundice-to-encephalopathy time between 2 and 12 weeks. O'Grady et al<sup>73 O'Grady J.G., Langley P.G., Isola L.M. , et al. Coagulopathy of fulminant hepatic failure Semin Liver Dis 1986 ;  6 : 159-163  [cross-ref]

Cliquez ici pour aller à la section Références</sup> proposed that acute liver failure (ALF) include the subcategories of hyperacute liver failure, for cases in which encephalopathy occurs within 7 days of the onset of jaundice, ALF per se, for patients with an interval between jaundice and encephalopathy of 7 to 28 days, and subacute liver failure for those with jaundice-to-encephalopathy times ranging between 5 and 12 weeks. In contrast with the original description, the classifications of both Bernuau et al and O'Grady et al allow the inclusion of cases with previously asymptomatic chronic liver conditions. In this article, FHF is used as a generic term encompassing this range of definitions.

In individual patients, the severity and duration of the clinical syndrome of FHF depends on the degree of impairment of synthetic, biotransformatory, and endotoxin-scavenging activity resulting from the loss of functioning liver tissue, on the systemic effects of toxins released from the necrotic liver, and on the extent and rate at which liver regeneration can occur. The nature of the initiating event influences both the histologic pattern of liver injury and the rate of progression of the clinical syndrome. Although advances in supportive medical care have had a substantial effect on survival, FHF, in its severest form, continues to carry a high mortality rate unless emergency orthotopic liver transplantation (OLT) is performed. A world-wide shortage of cadaveric donor organs, however, limits the use of OLT in the FHF setting, with many patients dying or developing contraindications to transplantation before a donor liver becomes available. To help overcome this problem, living related OLT has been introduced as a therapeutic option for FHF in pediatric and, more recently, in adult patients.<sup>46 Hattori H., Higuchi Y., Tsuji M. , et al. Living-related liver transplantation and neurological outcome in children with fulminant hepatic failure Transplantation 1998 ;  65 : 686-692  [cross-ref]

Cliquez ici pour aller à la section Références, 57 Lo M., Fan S.T., Liu C.L. , et al. Adult-to-adult living donor liver transplantation using extended right lobe grafts Ann Surg 1997 ;  226 : 261-270  [cross-ref]

Cliquez ici pour aller à la section Références</sup> Even for patients who undergo successful transplantation, the requirement for often long-term pharmacological immunosuppression, with the risk of serious side effects related to the use of such agents, means that OLT cannot be considered a panacea. Consequently, recent interest has centered on providing temporary liver support based on extracorporeal devices or hepatocyte transplantation, either as a bridge to OLT or, ideally, to allow time for or actively to promote native liver regeneration, on which spontaneous survival ultimately depends.

This article focuses on the spectrum of liver damage and regeneration in FHF, the pathophysiology of the resultant clinical syndrome, and the range of causative factors and their influence on both clinical manifestations and prognosis. Management issues, including specific supportive medical measures, indications for OLT, and the current status of temporary liver support strategies, are also discussed.