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Acute liver failure (ALF) in children is a rare clinical syndrome that evolves over a period of 8 weeks from the onset of signs and symptoms of liver disease. The clinical manifestations, resulting from massive necrosis and severe hepatocyte dysfunction affecting the synthetic, excretory, and detoxifying functions, include coagulopathy, jaundice, and hepatic encephalopathy. Toxins and inflammatory mediators released from necrotic liver cells add further insult and may lead to multiorgan failure. A practical definition of ALF suggested by the Pediatric Acute Liver Failure (PALF) study group is as follows: (1) biochemical evidence of acute liver injury; (2) no evidence of chronic liver disease; and (3) hepatic-based uncorrectable coagulopathy with an international normalized ratio (INR) ≥ 1.5 (approximate to a prothrombin time [PT] ≥ 15 seconds) with clinical hepatic encephalopathy or an INR ≥ 2.0 (approximate to PT ≥ 20 seconds) without encephalopathy due to a liver cause, not correctable by intravenous vitamin K. Hyperacute, acute, and subacute liver failure are defined as coagulopathy and encephalopathy developing within 1 week, 8 to 28 days, and 4 to 12 weeks within onset of jaundice, respectively. The mechanisms that underlie the poor regenerative response in ALF are not well defined. Massive destruction of hepatocytes may represent a direct cytotoxic effect (virus), accumulation of potentially hepatotoxic metabolites (drugs, inborn errors of metabolism), and oxidative damage (Wilson disease [WD]). Patchy or confluent, massive necrosis of hepatocytes is commonly found on liver biopsy or explant. Centrilobular necrosis is found in acetaminophen intoxication or circulatory shock. Microvesicular fatty change of hepatocytes is found in inborn errors of metabolism and valproate hepatotoxicity. Hepatocyte death may occur predominantly by apoptosis rather than by necrosis in some metabolic disorders. Liver biopsy is rarely helpful in ALF and may be risky because of the presence of coagulopathy. Children who develop ALF may have an underlying altered immune response that increases the risk of ALF and infections.
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CLINICAL MANIFESTATIONS
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Progressive jaundice, anorexia, vomiting, and abdominal pain are commonly observed in patients with ALF. Hepatic encephalopathy may be initially characterized by irritability, poor feeding, and a change in sleep rhythm in infants and disturbances of consciousness or motor functioning in older children. Recognition of hepatic encephalopathy is difficult and subtle and may only be apparent at the terminal stages (Table 419-1). Progression can occur over the course of a few days or even weeks. Bleeding from the gastrointestinal tract and easy bruising, as a result of severe coagulopathy, may be present; however, hypercoagulability has also been described as a consequence of poor synthesis of protein C and S. Other signs of liver dysfunction may include hypoglycemia and acidosis. ALF is a multisystem disorder affecting the brain (hepatic encephalopathy, cerebral edema, intracranial hypertension), cardiovascular system (systemic hypotension, high cardiac output, and subclinical myocardial injury), kidneys (hepatorenal syndrome), lungs (acute respiratory distress syndrome), blood (myelosuppression and poor immune function predisposing to sepsis), endocrine system (Addison disease), ...