LIVER DISEASE Acute Liver Failure Goal of Treatment Acute liver failure (ALF) in children occurs when the vital synthetic functions of the liver fail (coagulopathy) in the setting of known hepatic injury but without chronic liver disease ALF can be associated with hypoglycemia, hyperbilirubinemia, hypoproteinemia, and occasional encephalopathy Liver failure can develop acutely, or it may be chronically progressive ALF is a clinical syndrome due to a myriad of etiologies including infections (e.g., viral hepatitis) and metabolic diseases (e.g., Wilson disease) Clinical presentation can be quite variable The goal of the ED provider is early recognition of ALF in the setting of nonspecific signs and symptoms In patients with recognized liver failure, the ED physician should address acute and common complications such as electrolyte imbalances, hypoglycemia, and encephalopathy In addition, patients are often coagulopathic, which should be corrected in the setting of active bleeding If there is no active bleeding, correction of a coagulopathy should be weighed against the risk of volume overload Finally, patients with ALF are at very high risk for infection and should be treated aggressively if one is suspected CLINICAL PEARLS AND PITFALLS Childhood ALF may be diagnosed in the setting of coagulopathy, evidence of hepatic injury, and in the absence of chronic liver disease Children with ALF may not present with hepatic encephalopathy or asterixis Hypoglycemia is a common complication of ALF Coagulopathies in patients with ALF are difficult to correct and aggressive attempts at correction may lead to volume overload Renal function should be monitored closely Patients with ALF are at high risk for infectious complications and should be treated aggressively if infection is suspected Current Evidence ALF in children can be secondary to a variety of causes, however all result in the progression of irreversible hepatocyte injury In children younger than year of age, ALF most commonly occurs in the setting of a metabolic disease such as urea cycle disorders, galactosemia, type I tyrosinemia, or an underlying mitochondrial disorder (see Chapter 95 Metabolic Emergencies ) Other causes include viral hepatitis such as herpes simplex or enterovirus and medications such as acetaminophen In children older than year of age, the etiology is not determined in half of all cases ( Table 91.5 ) In identified cases, pharmaceutical agents such as acetaminophen or antiepileptic drugs are the most common causes Importantly, prolonged and inappropriate acetaminophen dosing is likely an important contributor to ALF in children, however it is much more difficult to assess with current testing mechanisms, which more accurately assesses for acute toxicity (see Chapter 102 Toxicologic Emergencies ) Metabolism of acetaminophen is known to be quite variable, and there are likely patients who are slow metabolizers that may increase their risk of ALF with prolonged use, even when correct weightbased dosing is given Other causes include autoimmune hepatitis and infections such as viral hepatitis Herbal drugs have also been known to cause ALF In developing countries, viral hepatitis is by far the most common etiology of ALF in all age groups of children TABLE 91.5 ETIOLOGY OF ACUTE LIVER FAILURE BY AGE GROUP Less than yr (%) >1 yr (%) Metabolic a (42) Unknown (47) Neonatal hemochromatosis (16) Undetermined (16) Viral hepatitis Non-A and non-B (27) Hepatitis A (10) Viral hepatitis (15) Hepatitis B (4) Other (10) Drug induced b (10) Other (2) a Type tyrosinemia, mitochondrial, urea cycle disorder, galactosemia, fructose intolerance amanita, isoniazid, valproic acid Adapted from Cochran JB, Losek JD Acute liver failure in children Pediatr Emerg Care 2007;23(2):129–135 b Acetaminophen, The development of hepatic encephalopathy (HE) is not seen in children as frequently as in adults, but when seen, is more common in patients with non– acetaminophen-induced ALF The Pediatric Acute Liver Failure Study Group evaluated children with ALF in North America and Europe and found that on presentation 57% of nonacetaminophen and 40% of acetaminophen groups had clinical evidence of HE Clinical Considerations Clinical Recognition Patients often not exhibit serious clinical features of ALF Patients may present with nonspecific prodromal symptoms or in septic shock Often children present with multisystem disease or sepsis, making the diagnosis of primary ALF challenging Adult definitions, which rely on HE, are often not reliable in children Triage Considerations Many patients simply present with nonspecific prodromal symptoms such as fatigue, nausea, and vomiting Others may present in shock with multisystem organ failure As with any life-threatening condition, patients should be triaged and treated accordingly Clinical Assessment Patients may initially complain of fatigue, nausea, vomiting, fever, and diffuse abdominal pain Occasionally, right upper quadrant pain is severe Commonly, a history of a prodromal viral illness can be elicited The presence of jaundice usually initiates the first visit to the physician As liver failure progresses, patients become more jaundiced and lethargic, and may report easy bruising or bleeding History should include any infectious and medication exposures including prescription and nonprescription medications and herbal and other alternative remedies ED physicians should be cognizant of chronic acetaminophen exposure in addition to acute toxicity Family history should be assessed for Wilson disease, α1 antitrypsin deficiency, autoimmune conditions, infant deaths, metabolic or mitochondria disorders, or liver failure of unknown etiology Physical examination findings may include small size, poor nutritional status, jaundice, bruising, or petechiae Hepatomegaly is common and some patients may have splenomegaly Findings associated with chronic liver disease and portal hypertension would suggest an alternative diagnosis Encephalopathy is graded on a scale from I to IV from drowsiness, poor concentration, and irritability to aggressive behavior or unresponsiveness Those with severe encephalopathy can develop cerebral edema and increased intracranial pressure (ICP) Cerebral edema is a major cause of death in patients with liver failure and requires aggressive supportive management Because it may be difficult to diagnose patients clinically, biochemical evidence of liver failure is necessary PT is a helpful measure of synthetic function Other laboratory markers suggestive of severe liver failure include evidence of increasing cholestasis manifested by a rising serum bilirubin level, hypoalbuminemia, and hypoglycemia It is also important to monitor serum transaminase levels Falling transaminase levels usually indicate resolving liver disease, although in the setting of increasing jaundice and coagulopathy, this trend may indicate excessive hepatocyte loss rather than hepatocyte recovery Serum fibrinogen is usually decreased in patients with liver failure In cases in which the patient has splenomegaly, thrombocytopenia and leukocytopenia may be present Hypoglycemia almost always accompanies ALF because the liver is the primary organ for gluconeogenesis and glycogen storage is often depleted This may complicate the signs of encephalopathy Hepatorenal syndrome occurs in approximately 75% of patients who reach severe encephalopathy The cause of hepatorenal syndrome is unclear; however, the result is oliguria ... as in adults, but when seen, is more common in patients with non– acetaminophen-induced ALF The Pediatric Acute Liver Failure Study Group evaluated children with ALF in North America and Europe