Acute liver failure: Summary of a workshop

Abstract

Acute liver failure (ALF) is a rare but challenging clinical syndrome with multiple causes; a specific etiology cannot be identified in 15% of adult and 50% of pediatric cases. The course of ALF is variable and the mortality rate is high. Liver transplantation is the only therapy of proven benefit, but the rapidity of progression and the variable course of ALF limit its use. Currently in the United States, spontaneous survival occurs in approximately 45%, liver transplantation in 25%, and death without transplantation in 30% of adults with ALF. Higher rates of spontaneous recovery (56%) and transplantation (31%) with lower rates of death (13%) occur in children. The outcome of ALF varies by etiology, favorable prognoses being found with acetaminophen overdose, hepatitis A, and ischemia (approximately 60% spontaneous survival), and poor prognoses with drug-induced ALF, hepatitis B, and indeterminate cases (approximately 25% spontaneous survival). Excellent intensive care is critical in management of patients with ALF. Nonspecific therapies are of unproven benefit. Future possible therapeutic approaches include N-acetylcysteine, hypothermia, liver assist devices, and hepatocyte transplantation. Advances in stem cell research may allow provision of cells for bioartificial liver support. ALF presents many challenging opportunities in both clinical and basic research.

Fig. 1

Etiology of ALF in the 1,147 adult patients who were enrolled in the U.S. ALF Study Group database between January 1998 and July 2007.

Fig. 2

Etiology of ALF in the 339 pediatric patients over the age of 3 years who were enrolled in the U.S. Pediatric ALF Study Group database between January 2000 and December 2006.

Fig. 3

Etiology of ALF in the 339 pediatric patients under the age of 3 years who were enrolled in the U.S. Pediatric ALF Study Group database between January 2000 and December 2006.

Fig. 4

Adjusted survival after liver transplantation for ALF versus chronic end-stage liver disease. Data adjusted for recipient age, gender, race, body mass index, medical condition, dialysis, diabetes, life-support, previous abdominal surgery, HCV-positivity, portal vein thrombosis, as well as donor factors including age, race, cause of death, DCD, cold ischemia time, partial or split liver and living donor. From the Scientific Registry of Transplant Recipients; December 2006.

Fig. 5

Adjusted survival after liver transplantation according to cause of ALF. Data adjusted for recipient age, gender, race, body mass index, medical condition, dialysis, diabetes, life-support, previous abdominal surgery, HCV-positivity, portal vein thrombosis, as well as donor factors including age, race, cause of death, DCD, cold ischemia time, partial or split liver, and living donor. Abbreviations: HAV, hepatitis A virus; HBV, hepatitis B virus; APAP, acetaminophen. From the Scientific Registry of Transplant Recipients; December 2006.

Fig. 6

Schematic representation of a closed bioartificial liver assist device. Isolated allogeneic or xenogeneic hepatocytes are separated from the patient’s circulation by a semipermeable membrane which avoids the need for immunosuppression. The membrane must be permeable from the patient’s circulation to the perfusate of the hepatocytes to allow passage of necessary nutrients as well as to the metabolic products (bilirubin, ammonia) that need to be detoxified by the hepatocytes. In the opposite direction, the membrane must be permeable to the proteins synthesized by the isolated liver cells as well as the detoxified products. Some nutrients, such as oxygen, are supplied directly to the hepatocytes particularly when high cell densities are used (not shown).

Fig. 7

Schematic representation of a hybrid liver assist device which employs both cellular and noncellular components for detoxification in an albumin-based extracorporeal perfusate circuit.