Acute liver failure (ALF) is an uncommon condition in which the rapid deterioration of liver function results in coagulopathy and alteration in the mental status of a previously healthy person. There are important differences between ALF in children and ALF in adults. The main difference is encephalopathy which may be absent, late, or unrecognized in children.

Pediatric acute liver failure (PALF) is a complex, rapidly progressive clinical syndrome that is the final common pathway for many disparate conditions, some known and others yet to be identified. The pediatric acut liver failure group recommended PALF definition as (1) evidence of liver dysfunction within 8 weeks of onset of symptoms (neonates may have only deranged liver functions without overt symptoms) (2) uncorrectable (6-8 hours after administration of one dose of parenteral vitamin K) coagulopathy with International Normalized Ratio (INR) >1.5 in patients with hepatic encephalopathy, or INR> 2.0 in patients without encephalopathy and (3) no evidence of chronic liver disease either at presentation or in the past. Staging of encephalopathy in infants and children is difficult as compared to adults. The group recommends the following grades: Grades I and II are indistinguishable with clinical features of inconsolable crying, inattention to task: with normal or exaggerated deep tendon reflexes: Grade III encephalopathy manifests as somnolence, stupor, combativeness and hyperreflexia. In grade IV, child is comatose [arousable with painful stimuli (IVa) or no response (IVb)] with absent reflexes and decerebration or decortication.

Incidence: The estimated frequency of acute liver failure (ALF) in all age groups in the United States is about 17 cases per 100,000 population per year, but the frequency in children is unknown. PALF accounts for 10 to 15 percent of pediatric liver transplants performed in the United States annually.

Etiology: The causes and natural history of ALF in neonates and infants differ from those in older children. In neonates, the commonest etiology reported in Western literature is neonatal hemochromatosis, Herpes simplex virus and less common causes are hemophagocytic lymphohistiocytosis and metabolic disorders (galactosemia, tyrosinemia, mitochondrial cytopathy). In infants, metabolic causes are common (type I tyrosinemia, mitochondrial cytopathy, galactosemia, and hereditary fructose intolerance). Drug-related hepatotoxicity, viral infections, autoimmune hepatitis, Wilson’sDisease are the main causes of ALF in older children. Nearly 15-20% of cases remain of indeterminate etiology.

Assessment and treatment: The most important step in the assessment of patients with acute liver failure is to identify the cause, as certain causes demand immediate and specific treatment. Planning for early transfer is important as the risks involved with patient transport may increase or even preclude transfer at later stages. The development of cerebral edema is the major cause of morbidity and mortality in patients with ALF. Another consequence of ALF is multisystem organ failure, which is often observed in the context of a hyperdynamic circulatory state that mimics sepsis; therefore, circulatory insufficiency and poor organ perfusion possibly either initiate or promote complications of ALF. So management should be in an intensive care setting in select situations. Patient should be monitorized hemodinamically. Electrolyte disturbances and hypoglycemia should be prevented with appropriate intravenous solution. Supportive management which included n-acetyl cystein and proton pump inhibitors is recommended in all cases of ALF irrespective of etiology. Despite coagulopathy is poor prognostic sign, routine correction of coagulopathy and thrombocytopenia is not recommended. Infection still remains one of the major causes of death in patients with ALF. The most commonly isolated organisms are gram-positive cocci (Staphylococci, Streptococci) and enteric gram-negative bacilli. Fungal infections, particularly Candida albicans, may be present in one third of patients with ALF. Empirical antibiotics are recommended for patients listed for liver transplantation (LT), since infection often results in delisting and immunosuppression post- LT is imminent. Though ammonia is an accepted triggering factor in cerebral edema, L-ornithine L-aspartate, lactulose and other non-absorbable antibiotics have not been found to be beneficial. However, if lactulose is administered (preferred in grades I-II HE) care should be taken to avoid over distension of the abdomen. Brain edema should be treated mannitol, hypertonic saline or head cooling.

Malnutrition affects pre- and post-transplant survival, and nutritional assessment should be a priority in children with liver disease. There is no role of protein restriction in children with HE. Energy intakes should be increased appropriately to counter the energy catabolism and also factor-in the requirement for maintenance, growth and physical activity.

Prognosis: Several prognostic scoring systems have been devised to predict mortality and to identify those requiring early LT. These include King’s College Hospital (KCH) criteria , pediatric end-stage liver disease (PELD) score, APACHE II, and Clichy criteria. However none of them is accepted ideal tool for determine to outcome.The outcome of acute liver failure is related to the etiology, the degree of encephalopathy, and related complications. Patients with ALF caused by acetaminophen have a better prognosis than those with an indeterminate form of the disorder. Patients with stage 3 or 4 encephalopathy have a poor prognosis. The risk of mortality increases with the development of any of the complications, which include cerebral edema, renal failure, adult respiratory distress syndrome (ARDS), and infection.

In more than 50% of children with ALF there is poor survival unless LT is offered at the appropriate time. Before LT, the mortality rate was generally greater than 80%.