PEDIATRIC ACUTE LIVER FAILURE – LIVER TRANSPLANTATION: THE OPPORTUNITY
Acute liver failure (ALF) is a devastating illness in a previously healthy child. The mortality rate may reach 80% to 90% in the absence of liver transplant. In some pediatric series, survival rates of 50% to 75% have been reported. Pediatric ALF is defined as a hepatic-based coagulopathy that is not corrected by parenteral administration of vitamin K; lack of evidence of chronic liver disease; and prothrombin time (PT) ≥20 seconds; or international normalized ratio (INR) ≥2, based on the consensus of the Pediatric Acute Liver Failure (PALF) Study Group.
In the presence of hepatic encephalopathy (HE), the thresholds for PT (15 s) and INR (1.5) may be reduced. Importantly, HE is not required for entry into the PALF study in patients with more severe coagulopathy because of the consensus among investigators that HE is difficult to diagnose in children. Unlike in adults, encephalopathy may be absent, late, or apparent only at the terminal stages in children. Thus, the emphasis in children is placed on the presence of significant coagulopathy in the absence of sepsis or disseminated intravascular coagulation. The subsequent development of brain edema is a leading cause of death, and according to the PALF study, the spontaneous recovery rate of patients with grade 3 to 4 HE is only 25%.
The etiological diagnoses vary and in most cases cannot be determined. The etiology of ALF in infants and children can be grouped into several broad categories that include infections, shock, immune dysregulation, toxins and medications (e.g., acetaminophen), and metabolic disorders. ALF in children differs around the world. In the developing world and in certain communities in developed countries, hepatitis A and E are the most important etiologic agents causing ALF in children. Hepatitis B virus (HBV) infection is an important cause of fulminant hepatic failure (FHF) in certain endemic areas. In developed countries, the cause of FHF differs according to age and geographic location. In English infants younger than 2 years of age, hemophagocytic lymphohistiocytosis, cryptogenic hepatitis, and metabolic diseases account for 75% of cases, and infectious causes were rare. In contrast, in France, undetermined viral infection and drug-induced liver injury are likely important causes. ALF can be associated with rapidly progressive multiorgan failure with devastating complications. Nonspecific therapies have not been proven to be beneficial for the recovery from ALF, and liver transplantation is presently the only option for treating irreversible ALF.
Children usually present with a hepatitis-like clinical picture; jaundice is the most common symptom in most patients. Children with ALF are critically ill, and the level of consciousness rapidly deteriorates as symptoms become worse. Over a few days to weeks, the condition turns into a coma, with the development of ascites, cerebral edema, and decorticate and decerebrate posturing.
A range of laboratory studies is required to determine the etiology, severity, and prognosis in pediatric patients. Liver ...