Acute Hepatic Failure in Children
Introduction to Acute Hepatic Failure in Children
Acute hepatic failure (AHF) in children, also known as acute liver failure, is a rare but life-threatening condition characterized by rapid deterioration of liver function. It is defined by the onset of coagulopathy and hepatic encephalopathy within 8 weeks of the first symptoms in a patient without pre-existing liver disease.
Key features include:
- Sudden onset of severe liver dysfunction
- Coagulopathy (INR ≥ 1.5 not corrected by vitamin K)
- Hepatic encephalopathy (any degree)
- No prior history of liver disease
AHF in children differs from adults in several aspects, including etiology, clinical presentation, and management strategies. Early recognition and prompt intervention are crucial for improving outcomes.
Etiology of Acute Hepatic Failure in Children
The causes of AHF in children vary by age and geographical location. Common etiologies include:
- Infectious causes:
- Viral hepatitis (A, B, E, non-A-E)
- Other viruses (EBV, CMV, HSV, adenovirus, parvovirus B19)
- Sepsis
- Metabolic disorders:
- Wilson's disease
- Galactosemia
- Tyrosinemia type 1
- Mitochondrial disorders
- Drug-induced liver injury:
- Acetaminophen toxicity
- Idiosyncratic drug reactions (e.g., valproic acid, isoniazid)
- Autoimmune hepatitis
- Vascular disorders:
- Budd-Chiari syndrome
- Ischemic hepatitis
- Toxins (e.g., Amanita phalloides mushroom poisoning)
- Indeterminate (up to 50% of cases in some series)
The distribution of etiologies varies with age. In neonates, metabolic and infectious causes predominate, while in older children and adolescents, drug-induced liver injury and autoimmune hepatitis become more common.
Clinical Presentation of Acute Hepatic Failure in Children
The clinical presentation of AHF in children can be nonspecific initially and may progress rapidly. Key features include:
- Prodromal symptoms:
- Fatigue
- Nausea and vomiting
- Abdominal pain
- Anorexia
- Jaundice: Often a late sign, may be absent in some cases
- Hepatic encephalopathy:
- Grade I: Mild confusion, altered mood
- Grade II: Drowsiness, inappropriate behavior
- Grade III: Stupor, marked confusion
- Grade IV: Coma, unresponsive to pain
- Coagulopathy: Easy bruising, bleeding
- Ascites and edema
- Hepatomegaly or liver atrophy (depending on the stage and etiology)
- Systemic complications:
- Cardiovascular: Hypotension, tachycardia
- Respiratory: Tachypnea, respiratory failure
- Renal: Acute kidney injury, hepatorenal syndrome
- Metabolic: Hypoglycemia, electrolyte imbalances
- Infection: Increased susceptibility to bacterial and fungal infections
The progression of symptoms can be rapid, and children may deteriorate quickly from apparent wellness to critical illness within days.
Diagnosis of Acute Hepatic Failure in Children
Diagnosing AHF in children requires a combination of clinical assessment, laboratory tests, and imaging studies:
- Clinical evaluation:
- Detailed history, including potential exposures and medications
- Physical examination, focusing on signs of liver dysfunction and encephalopathy
- Laboratory tests:
- Liver function tests: Elevated AST, ALT, bilirubin; low albumin
- Coagulation studies: Prolonged PT/INR, aPTT
- Complete blood count
- Renal function tests
- Electrolytes, glucose
- Ammonia levels
- Viral serologies (HAV, HBV, HCV, EBV, CMV, HSV)
- Autoimmune markers (ANA, ASMA, LKM-1 antibodies)
- Metabolic screening: Serum amino acids, urine organic acids, acylcarnitine profile
- Toxicology screen, including acetaminophen levels
- Imaging studies:
- Abdominal ultrasound with Doppler
- CT or MRI of the abdomen (if indicated)
- Brain imaging to evaluate for cerebral edema
- Liver biopsy: May be considered if the diagnosis is unclear, but risks should be carefully weighed
Early consultation with a pediatric hepatologist and a liver transplant center is crucial for optimal management and timely consideration of liver transplantation if needed.
Management of Acute Hepatic Failure in Children
Management of AHF in children is complex and often requires a multidisciplinary approach in a pediatric intensive care unit. Key components include:
- Supportive care:
- Fluid and electrolyte management
- Nutritional support (often enteral feeding)
- Correction of coagulopathy (FFP, cryoprecipitate as needed)
- Management of hepatic encephalopathy
- Prevention and treatment of infections
- Specific treatments:
- N-acetylcysteine for acetaminophen toxicity
- Antiviral therapy for viral hepatitis
- Steroids for autoimmune hepatitis
- Specific treatments for metabolic disorders (e.g., penicillamine for Wilson's disease)
- Management of complications:
- Cerebral edema: Mannitol, hypertonic saline, hypothermia
- Renal failure: Continuous renal replacement therapy
- Cardiovascular support: Vasoactive medications
- Respiratory support: Mechanical ventilation if needed
- Liver transplantation:
- Early evaluation for transplant candidacy
- Timely listing and transplantation if indicated
- Emerging therapies:
- Hepatocyte transplantation
- Bioartificial liver support devices
- Plasma exchange
Close monitoring and frequent reassessment are crucial, as the clinical status can change rapidly. The decision for liver transplantation should be made early, based on prognostic criteria and the overall clinical picture.
Prognosis of Acute Hepatic Failure in Children
The prognosis of AHF in children has improved significantly with advances in critical care management and liver transplantation. However, outcomes can vary widely depending on the etiology, severity, and timeliness of interventions.
- Spontaneous recovery: Occurs in about 40-50% of cases
- Liver transplantation: Required in approximately 30-40% of cases
- Mortality: Overall mortality ranges from 20-30%, but can be higher in certain etiologies
Prognostic factors include:
- Etiology: Better outcomes in acetaminophen toxicity and hepatitis A; worse in indeterminate cases
- Age: Infants generally have poorer outcomes
- Degree of encephalopathy: Higher grades associated with worse prognosis
- Coagulopathy: Severe coagulopathy indicates poor prognosis
- Presence of multiorgan failure
- Rapid disease progression
Several prognostic scoring systems have been developed to aid in decision-making for liver transplantation, including the King's College Criteria and the Pediatric End-Stage Liver Disease (PELD) score. However, these should be used in conjunction with clinical judgment and not as sole determinants of management decisions.
Long-term follow-up is essential for survivors, as some may develop chronic liver disease or neurological sequelae, particularly if they experienced severe hepatic encephalopathy.
Acute Hepatic Failure in Children
- What is the definition of acute liver failure in children?
Severe liver dysfunction without pre-existing liver disease, developing within 8 weeks of onset of symptoms - Which age group is most commonly affected by acute liver failure in children?
Infants and young children under 5 years old - What is the most common cause of acute liver failure in children in developed countries?
Acetaminophen (paracetamol) toxicity - Which viral infection is a leading cause of acute liver failure in children in developing countries?
Hepatitis A virus - What is the hallmark clinical sign of acute liver failure?
Hepatic encephalopathy - Which laboratory test is used to assess the liver's synthetic function in acute liver failure?
Prothrombin time (PT) or International Normalized Ratio (INR) - What is the significance of elevated ammonia levels in acute liver failure?
It indicates impaired liver function and is associated with hepatic encephalopathy - Which imaging technique is commonly used to evaluate liver size and texture in acute liver failure?
Ultrasound - What is the primary goal of management in acute liver failure?
To support organ systems and prevent complications while the liver potentially recovers - Which metabolic derangement is common in acute liver failure and requires close monitoring?
Hypoglycemia - What is the role of N-acetylcysteine (NAC) in treating acute liver failure?
It serves as an antidote for acetaminophen toxicity and may benefit non-acetaminophen causes - Which complication of acute liver failure can lead to increased intracranial pressure?
Cerebral edema - What is the significance of coagulopathy in acute liver failure?
It indicates decreased synthesis of clotting factors by the liver and increases bleeding risk - Which renal complication is common in acute liver failure?
Hepatorenal syndrome - What is the role of lactulose in managing acute liver failure?
It helps reduce ammonia levels and manage hepatic encephalopathy - Which nutritional approach is typically recommended in acute liver failure?
Enteral nutrition with a high-carbohydrate, low-protein diet - What is the purpose of prophylactic antibiotics in acute liver failure?
To prevent and treat infections, which are common complications - Which scoring system is commonly used to assess the severity and prognosis of acute liver failure in children?
Pediatric End-stage Liver Disease (PELD) score - What is the role of liver transplantation in acute liver failure?
It is the definitive treatment for cases that fail to improve with medical management - Which factor is associated with a poor prognosis in acute liver failure?
Grade III or IV hepatic encephalopathy - What is the approximate survival rate for children with acute liver failure who undergo liver transplantation?
70-80% - Which metabolic liver disease can present as acute liver failure in infants?
Galactosemia - What is the role of plasma exchange in managing acute liver failure?
It may help remove toxins and provide coagulation factors - Which medication is contraindicated in acute liver failure due to its potential to worsen encephalopathy?
Benzodiazepines - What is the significance of elevated alpha-fetoprotein (AFP) levels in acute liver failure?
It may indicate ongoing liver regeneration - Which electrolyte disturbance is common in acute liver failure and requires close monitoring?
Hyponatremia - What is the role of continuous renal replacement therapy (CRRT) in acute liver failure?
It helps manage fluid overload, electrolyte imbalances, and remove toxins - Which hepatotoxic mushroom can cause acute liver failure in children?
Amanita phalloides (death cap mushroom) - What is the significance of liver biopsy in the management of acute liver failure?
It may help determine the etiology and assess the extent of liver damage - Which autoimmune condition can present as acute liver failure in children?
Autoimmune hepatitis
