Acute liver failure is a complex multi system disorder of potentially devastating consequences, resulting from an acute severe insult to the liver. The currently accepted Pediatric definition is – “It is a multi-system disorder in which severe impairment of liver cell function, with or without encephalopathy, occurs in association with hepatocellular necrosis in a patient with no recognisable underlying chronic liver disease”.The classification of liver failure is based on the time interval between jaundice and onset of encephalopathy.
Hyper acute liver failure – when it occurs within one week.
Acute liver failure – if it occurs between 1- 4 weeks.
Sub-acute liver failure – if it occurs between 5 - 12 weeks.
Encephalopathy is acute and usually evolves over a few days and progresses through stages of drowsiness, hypersomnia, unresponsiveness and eventually, coma.
2. Cerebral Edema
Cerebral edema develops in all patients with stage IV encephalopathy. Pupillary abnormalities, muscular rigidity, decerebrate posturing, focal seizures and loss of brain stem reflexes are clinical indicators.
3. Coagulopathy and Bleeding
Failure in hepatic synthesis of clotting and fibrinolytic factors; altered platelet numbers and function; and intra-vascular coagulation may be responsible for coagulopathy. Bleeding from the upper gastro-intestinal tract is most common manifestation.
Majority of children with acute liver failure will have low blood glucose levels (< 40 mg/dl) at some time during the illness. Hypoglycemia worsens encephalopathy and also contributes to dysfunction of other organs.
5. Renal Dysfunction
Functional renal failure (Hepato-renal Syndrome) occurs in a majority of children with FHF. Features include acute sodium retention (urinary spot Na < 20 mEq/L), normal urinary sediment and oliguria (< 1 ml / kg / hr). Acute tubular necrosis (ATN) may occur in some cases.
6. Electrolyte Disturbances
Hyponatremia (low sodium level in body) as well as hypokalemia (low potassium level in body) are known to occur in patients with acute liver failure.
7. Cardiovascular and Pulmonary Complications
Most children with severe FHF have significant hypotension. Many of them have decreased vascular resistance and clinical features of “Warm Shock”. Profound hypotension with metabolic acidosis indicates poor prognosis in FHF. Most such children require mechanical ventilation.
Sepsis complicates ALF in more than 50% of children. Intensive care support with invasive modalities is partly responsible. Alteration in the immune system in FHF is also an important factor. Complicating septicemia increases the risk of morbidity and mortality.
Etiology of Acute Liver Failure
Acute liver failure is the end result of a variety of insults to the liver of which Acute viral hepatitis is the commonest identified cause. Hepatitis A and E viruses, however, predominate in developing countries. Drugs are the next most common cause, with Valproate, Paracetamol and INH being implicated. Iron poisoning can also result in fulminant hepatitis. Galactosemia, tyrosinemia and hereditary fructose intolerance can present as FHF in infants and young children. Wilson’s disease is important precipitating factor in children above 8 years of age. Herpes Virus, Echo Virus, Cytomegalovirus and perinatal haemochromatosis are the commonest causes of neonatal liver failure.
Management is aimed at life support as well as prevention and treatment of complications, to facilitate recovery of the liver. Older children with delirium are aggressive and therefore, restraint and sedation may be necessary in them. Sedatives other than benzodiazepines may be used. A naso-gastric tube should be in place, and drained by gravity. Regular gentle saline washes will detect upper gastrointestinal hemorrhage. Urine output should be strictly monitored. A central venous catheter helps monitor central venous pressure. An indwelling arterial line can monitor blood pressure as well as enable blood sampling. Clinical neurologic evaluation should be done twice daily to follow the course of the encephalopathy.
1. Management of encephalopathy
A hypertonic enema should be given soon after admission to evacuate the colonic contents. Subsequently, the large bowel should be washed out twice daily. Lactulose, a cathartic agent, should be administered through the nasogastric tube. Oral neomycin or ampicillin will sterilise the gut and prevent ammonia production.
2. Provision of Protein and Calories
Calories are provided by a constant 10% dextrose infusion. Protein intake must be limited to 0.5 – 1.0 gm / kg / day. Parenteral nutrition can reduce ammonia production.
3. Fluid and Electrolyte Balance
Strict records of intake and output, frequent electrolyte monitoring and assessment of central venous pressure are essential. Maintenance fluid is usually 10% dextrose with 1 mEq/kg/day of sodium. The fluid volume should be close to the normal maintenance requirement, and should be adjusted depending on the Central Venous Pressure and urine output.
4. Coagulopathy and Anemia
Coagulopathy should be corrected if there is clinically obvious bleeding. Fresh frozen plasma infusion is recommended.
5. Hypoxia and Respiratory Acidosis
Early mechanical ventilation is ideal. Gentle intubation and handling is essential and pulmonary hemorrhage should be watched for.
6. Increased Intra-Cranial Pressure
Aggressive management of increased Intracranial pressure (I.C.P) is essential. Osmotic agents like mannitol are preferred. Furosemide acts synergistically with mannitol.
7. Ensuring Urine Output
Pre-renal failure may be managed initially with a fluid challenge followed by adequate fluid administration to maintain C.V.P. Loop diuretics like furosemide can be used in mild renal dysfunction. Dopamine helps maintain renal perfusion. If the urine output is persistently below 1 ml / kg / hr and diminishing, dialysis should be considered.
Cultures should be obtained from all indwelling catheters as well as blood. Chest radiographs should be done at least once on alternate days. Wide-spectrum intravenous antibiotics, which are not hepatotoxic can be chosen for empiric therapy until culture results are available.
Acetylcysteine replenishes depleted glutathione stores in the liver. It is beneficial in FHF caused by Paracetamol poisoning, but may be useful in other causes as well. However, it is effective only if administered within 12 –15 hours after the drug ingestion.
B. Temporary Hepatic Support
The aim is to support the patient and prevent neurological impairment and complications. Many approaches have been tried – plasmapheresis; exchange transfusions; extra-corporal blood cleansing with activated charcoal and other binding resins; liver assisting devices containing cultured hepatocytes; and cross-circulation with animals.
C. Liver Transplantation
Liver transplantation offers the best life-saving potential. The prohibitive cost and shortage of donors limits the practical use of this mode of therapy in developing countries. Success rates with liver transplantation in FHF are lower than that for other indications.
Although there are no reliable criteria to predict the outcome of ALF in children, the prognosis is generally better than that in adults. Drug induced FHF, particularly Paracetamol overdose, has a better prognosis than viral hepatitis. Hepatitis A infection is generally associated with better survival. The higher the grade of encephalopathy, the poorer is the outcome.
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