TY - CHAP M1 - Book, Section TI - Acute Liver Failure A1 - Miloh, Tamir A1 - Desai, Moreshwar A2 - Kline, Mark W. Y1 - 2018 N1 - T2 - Rudolph's Pediatrics, 23e AB - 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. SN - PB - McGraw-Hill Education CY - New York, NY Y2 - 2024/03/28 UR - accesspediatrics.mhmedical.com/content.aspx?aid=1182909271 ER -