Acute Liver Failure Year 4 Paediatrics Notes OmpathStudy

Acute Liver Failure Year 4 · Paediatrics Collection: 4TH YEAR ALL NOTES / PAEDS / PAEDS 4.2 / MUNGE / GIT -- Slide 1 Acute Liver Failure Dr Rose Munge Slide 2 Acute liver failure is a clinical syndrome resulting from massive necrosis of hepatocytes or from severe functional impairment of hepatocytes.\n The synthetic, excretory, and detoxifying functions of the liver are all severely impaired.\n The accepted definition in children includes biochemical evidence of acute liver injury (usually <8 wk duration); no evidence of chronic liver disease; and hepatic-based coagulopathy defined as a prothrombin time (PT) 15 sec or international normalized ratio (INR) 1.5 not corrected by vitamin K in the presence of clinical hepatic encephalopathy, or a PT 20 sec or INR 2 regardless of the presence of clinical hepatic encephalopathy. Slide 3 Liver failure in the perinatal period can be associated with prenatal liver injury and even cirrhosis.\nExamples include gestational alloimmune liver disease (GALD), tyrosinemia, familial hemophagocytic lymphohistiocytosis (HLH), and some cases of congenital viral (herpes simplex virus [HSV]) infection.\nLiver disease may be noticed at birth or after several days of apparent well-being. Fulminant Wilson disease and fulminant autoimmune hepatitis also occurs in older children who were previously asymptomatic but, by definition, have preexisting liver disease. Slide 4 Other forms of acute-on-chronic liver failure can occur when a patient with an underlying liver disease such as biliary atresia develops hepatic decompensation after viral or drug-induced hepatic injury.\n In some cases of liver failure, particularly in the idiopathic form of acute hepatic failure, the onset of encephalopathy occurs later, from 8 to 28 wk after the onset of jaundice. Slide 5 Aetiology Infection Acute hepatic failure can be a complication of viral hepatitis (A, B, D, and rarely E), Epstein-Barr virus, herpes simplex virus, adenovirus, enterovirus, influenza A, cytomegalovirus, parvovirus B19, human herpesvirus-6, varicella zoster infection, parechovirus, and other respiratory illnesses.\nAutoimmune Hepatitis\nAcute hepatic failure is caused by autoimmune hepatitis in approximately 5% of cases. Patients have a positive autoimmune marker (e.g., antinuclear antibody, anti–smooth muscle antibody, liver-kidney microsomal antibody, or soluble liver antigen) and possibly an elevated serum immunoglobulin G level. Slide 6 Metabolic Diseases Wilson disease, acute fatty liver of pregnancy, galactosemia, hereditary tyrosinemia, hereditary fructose intolerance, defects in β-oxidation of fatty acids, and deficiencies of mitochondrial electron transport, in particular mitochondrial DNA depletion disorders. Neoplasm Acute liver failure can occur with malignancies including leukemia, lymphoma, and familial HLH. Slide 7 Gestational Alloimmune Liver Disease GALD is the most common cause of acute liver failure in the neonate. In this alloimmune process, maternal immunoglobulin (Ig) G antibodies bind to fetal liver antigens and activate the terminal complement cascade resulting in hepatocyte injury and death.\nDrug-Induced Liver Injury Various hepatotoxic drugs and chemicals can also cause drug-induced liver injury and acute hepatic failure. Predictable liver injury can occur after exposure to carbon tetrachloride, Amanita phalloides mushrooms or after acetaminophen overdose. Acetaminophen is the most common identifiable etiology of acute hepatic failure in children and adolescents. Damage can follow the use of halothane, isoniazid, ecstasy, or sodium valproate, herbal and weight loss supplements. Slide 8 Vascular Ischemia and hypoxia resulting from hepatic vascular occlusion, severe heart failure, cyanotic congenital heart disease, or circulatory shock can produce liver failure. Idiopathic Acute Liver Failure Idiopathic acute liver failure accounts for 40–50% of acute hepatic failure cases in children. The disease occurs sporadically and usually without the risk factors for common causes of viral hepatitis. Slide 9 Pathology Liver biopsy usually reveals patchy or confluent massive necrosis of hepatocytes. Multilobular or bridging necrosis can be associated with collapse of the reticulin framework of the liver.\nThere may be little or no regeneration of hepatocytes.\nA zonal pattern of necrosis may be observed with certain insults. Centrilobular damage is associated with acetaminophen hepatotoxicity or with circulatory shock.\nEvidence of severe hepatocyte dysfunction rather than cell necrosis is occasionally the predominant histologic finding (microvesicular fatty infiltrate of hepatocytes is observed in Reye syndrome, β-oxidation defects, and tetracycline toxicity). Slide 10 Pathogenesis The mechanisms that lead to acute hepatic failure are poorly understood.\nWhatever the initial cause of hepatocyte injury, various factors can contribute to the pathogenesis of liver failure, including impaired hepatocyte regeneration, alte