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 (Ϸ60% spontaneous survival), and poor prognoses with drug-induced ALF, hepatitis B, and indeterminate cases (Ϸ25% 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. A cute liver failure (ALF) is a dramatic but rare clinical syndrome marked by the sudden loss of hepatic function in a person with no prior history of liver disease. The causes of ALF include viral hepatitis, drug-induced and toxin-induced liver disease, metabolic errors, ischemia, and miscellaneous rare causes. Currently, there are no specific therapies of proven benefit except for emergency liver transplantation. The many challenges in understanding and management of ALF led to the organization of a 2-day research workshop held on December 4-5, 2006 in Bethesda, Maryland, sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) with support from the National Institute of Biomedical Imaging and Bioengineering (NIBIB) and the Office of Rare Diseases of the National Institutes of Health (NIH). This manuscript summarizes the presentations at that meeting and the recommendations arising therefrom. Overview of ALF Epidemiology and Etiology in AdultsThe sudden loss of hepatic function in a person without preexisting liver disease defines ALF. 1,2 The most reliable signs of severe acute liver injury are the presence of coagulopathy (international normalized ratio [INR] Ն 1.5) and any degree of hepatic encephalopathy, the length of illness being considered anything Յ 24 weeks. Many patients evolve to coma within 1 week or less. The term "acute liver failure" is preferable to fulminant hepatic failure 1 or acute hepatic necrosis. 2 ALF is rare and represents a syndrome rather than a specific disease, having multiple causes that vary in course and outcome. 1401The rarity of ALF and its unpredictable, severe course make it a challenging entity for prospec...

Management in Acute Liver Failure

“…High doses of NAC are recommended in such patients and should be started within 48 h of ingestion. 5 Pregnancy and acute liver failure: There is increased risk of maternal and fetal complications in pregnant patients with ALF. 81 The principles of management of abortions, preterm labor, premature rupture of membranes and still birth remain unchanged.…”

“…1 However, the interval between onset of acute hepatic injury (jaundice) and onset of liver failure (encephalopathy with or without coagulopathy) in such patients (icterus-encephalopathy interval; IEI) has been described to be between 4 weeks (Indian definition) [2][3][4] to 24 weeks (AASLD-ALF study group). 5 Further, due to the diverse natural course, ALF has been sub-classified as hyperacute (IEI # 7 day), acute (IEI # 4 weeks) and sub-acute ALF (IEI $ 5 week to #12 weeks) by British authors. 6 Despite these differences in definitions, the central and most important clinical event in ALF is occurrence of hepatic encephalopathy (HE) and cerebral edema which is responsible for most of the fatalities in this serious clinical syndrome.…”

Freshly isolated hepatocyte transplantation in acetaminophen-induced hepatotoxicity model in rats

“…In our study, animals had the ALT levels peak at day 1, started to decrease at day 2 and had returned to basal values at day 3. Lee et al (12) , analyzing 1,147 cases of APAP-induced ALF in humans demonstrated that ALT levels are very high (2,138 to 6,731). However, in APAP-induced hepatotoxicity in rats ALT levels are lower in comparison with humans, around of 256.5 ± 11.2 (23) .…”

“…Acetaminophen (APAP) toxicity is the leading cause of ALF in the United States and United Kingdom, accounting for 46% and 70% of cases, respec-tively (12,24) . The mechanism of liver toxicity is well established.…”

A new experimental model for acute hepatic failure in rats

“…Despite several advances in the clinical management of patients with acute liver failure (ALF), this condition remains extremely serious and results in high mortality rates. Viral hepatitis and drug-induced hepatotoxicity (in particular acetaminophen overdose) are the most frequent causes of ALF, although their relative incidence varies markedly in different parts of the world 1 . The difficulties inherent to the management of patients with ALF can be explained in part by the serious systemic and neurological complications of ALF, which include hypoglycemia, renal failure, coagulopathy, sepsis, multiorgan failure, intracranial hypertension, and hepatic encephalopathy 2 .…”