- Treatment
Specific therapies for identifiable causes of acute liver failure include N-acetylcysteine (acetaminophen), acyclovir (HSV), penicillin (Amanita mushrooms), lamivudine (HBV), prednisone (autoimmune hepatitis), and pleconaril (enteroviruses).
Management of other types of fulminant hepatic failure is supportive. No therapy is known to reverse hepatocyte injury or to promote hepatic regeneration.
An infant or child with acute hepatic failure should be cared for in an institution able to perform a liver transplantation if necessary and managed in an intensive care unit with continuous monitoring of vital functions
Endotracheal intubation may be required to prevent aspiration, to reduce cerebral edema by hyperventilation, and to facilitate pulmonary toilet. Mechanical ventilation and supplemental oxygen are often necessary in advanced coma
Sedatives should be avoided unless needed in the intubated patient because these agents can aggravate or precipitate encephalopathy. Opiates may be better tolerated than benzodiazepines. Prophylactic use of proton pump inhibitors should be considered because of the high risk of gastrointestinal bleeding
Treatment
Hypovolemia should be avoided and treated with cautious infusions of isotonic fluids and blood products. Renal dysfunction can result from dehydration, acute tubular necrosis, or functional renal failure (hepatorenal syndrome). Electrolyte and glucose solutions should be administered intravenously to maintain urine output, to correct or prevent hypoglycemia, and to maintain normal serum potassium concentrations. Hyponatremia is common and should be avoided, but it is usually dilutional and not a result of sodium depletion.
Parenteral supplementation with calcium, phosphorus, and magnesium may be required. Hypophosphatemia, probably a reflection of liver regeneration, and early phosphorus administration are associated with a better prognosis in acute liver failure, whereas hyperphosphatemia predicts a failure of spontaneous recovery
Coagulopathy should be treated with parenteral administration of vitamin K and can require infusion of fresh frozen plasma, cryoprecipitate, and platelets to treat clinically significant bleeding; disseminated intravascular coagulation can also occur. Plasmapheresis can permit temporary correction of the bleeding diathesis without resulting in volume overload. Recombinant factor VIIa has been used for transient correction of coagulopathy refractory to fresh frozen plasma infusions and can facilitate the performance of invasive procedures such as placement of a central line or an intracranial pressure monitor. Continuous hemofiltration is useful for managing fluid overload and acute renal failure.
Patients should be monitored closely for infection, including sepsis, pneumonia, peritonitis, and urinary tract infections. At least 50% of patients experience serious infection. Gram-positive organisms (Staphylococcus aureus, S. epidermidis) are the most common pathogens, but gram-negative and fungal infections are also observed
Gastrointestinal hemorrhage, infection, constipation, sedatives, electrolyte imbalance, and hypovolemia can precipitate encephalopathy and should be identified and corrected. Protein intake should be initially restricted or eliminated, depending on the degree of encephalopathy. The gut should be purged with several enemas. Lactulose should be given every 2-4 hr orally or by nasogastric tube in doses (10-50 mL) sufficient to cause diarrhea. The dose is then adjusted to produce several acidic, loose bowel movements daily. Lactulose syrup diluted with 1-3 volumes of water can also be given as a retention enema every 6 hr. Lactulose, a nonabsorbable disaccharide, is metabolized to organic acids by colonic bacteria; it probably lowers blood ammonia levels through decreasing microbial ammonia production and through trapping of ammonia in acidic intestinal contents.
Oral or rectal administration of a nonabsorbable antibiotic such as rifaximin or neomycin can reduce enteric bacteria responsible for ammonia production. Oral antibiotics may be more effective than lactulose in lowering serum ammonia levels. Flumazenil, a benzodiazepine antagonist, can temporally reverse early hepatic encephalopathy. N-Acetylcysteine has also been effective in improving the outcome of patients with acute liver failure not associated with acetaminophen.
Cerebral edema is an extremely serious complication of hepatic encephalopathy that responds poorly to measures such as corticosteroid administration and osmotic diuresis. Monitoring intracranial pressure can be useful in preventing severe cerebral edema, in maintaining cerebral perfusion pressure, and in establishing the suitability of a patient for liver transplantation. Controlled trials have shown a worsened outcome of fulminant hepatic failure in patients treated with corticosteroids.
Temporary liver support continues to be evaluated as a bridge for the patient with liver failure to liver transplantation or regeneration. Nonbiologic systems, essentially a form of liver dialysis with an albumin-containing dialysate, and biologic liver support devices that involve perfusion of the patient’s blood through a cartridge containing liver cell lines or porcine hepatocytes can remove some toxins, improve serum biochemical abnormalities, and, in some cases, improve neurologic function, but there has been little evidence of improved survival, and few children have been treated.
Orthotopic liver transplantation (OLT) can be lifesaving in patients who reach advanced stages (III, IV) of hepatic coma. Reduced-size allografts and living donor transplantation have been important advances in the treatment of infants with hepatic failure.
Partial auxiliary orthotopic or heterotopic liver transplantation is successful in a small number of children, and in some cases it has allowed regeneration of the native liver and eventual withdrawal of immunosuppression.
OLT should not be done in patients with liver failure and neuromuscular dysfunction secondary to a mitochondrial disorder because progressive neurologic deterioration is likely to continue after transplant.
Dr. Jayaprakash
Superintendent, ICH.
Institute of Child Health.
Gov. Medical College Kottayam.
Kerala, India.