Pediatric Fulminant Hepatic Failure Treatment & Management

Reaching a diagnosis of fulminant hepatic failure (FHF) is of vital importance so that appropriate and early treatment can be initiated. Unfortunately, in most patients, no definitive therapy that can result in regeneration of hepatocytes or reversal of injury is available. ^[21]

Provide symptomatic treatment and life support. Direct treatment toward the specific cause of FHF when an identifiable etiology is found. Avoid nephrotoxic agents, benzodiazepines, and other sedative medications. An intensive care unit (ICU) and pediatric hepatology setting with facilities for liver transplantation should be available for proper diagnosis and management.

General supportive care includes correction of any fluid and electrolyte imbalances and management of hypoglycemia if present.

Correction of Fluid and Electrolyte Abnormalities

Avoid fluid overload (restrict hydration up to 2 mL/kg/h). Hemodynamic monitoring of central pressures is advised to assess volume depletion and overload.

Monitor electrolytes and correct any disturbances. Patients may require intravenous administration of calcium, phosphorus, or magnesium.

Management of Hypoglycemia

Monitor blood glucose regularly for possible complicating hypoglycemia, and treat with intravenous glucose administration. An infusion of 10-20% of glucose is usually required.

Parenteral vitamin K and plasmapheresis are needed to correct coagulopathy and prevent its serious sequelae. However, unless acute hemorrhage is present or an invasive procedure is performed, empiric transfusion with fresh frozen plasma (FFP) is not warranted. It can present a significant volume challenge to the kidneys.

Platelet transfusion may be indicated in severe cases of FHF with coagulopathy and thrombocytopenia. It occasionally is required to maintain a platelet count of greater than 50,000.

A parenteral H₂ -receptor blocker is administered prophylactically to prevent potential GI bleeding.

Hepatitis is treated with acyclovir for herpesvirus hepatitis and with prednisone and azathioprine for autoimmune hepatitis.

Acetaminophen overdose is treated with an antidote for hepatotoxicity (ie, N -acetylcysteine).

Galactosemia and fructosemia are treated with dietary elimination. Hereditary tyrosinemia type I is treated with dietary elimination and 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC).

Renal dysfunction with renal failure occurs in as many as 50% of patients. Kidneys are involved secondary to hepatorenal syndrome (HRS), acute tubular necrosis (ATN), drug-induced nephrotoxicity, or prerenal azotemia. Therefore, monitoring fluids and renal function tests is important.

Maintain urine output. Focus on management of renal impairment due to HRS or ATN.

Management of Hepatorenal Syndrome

HRS is defined as functional renal failure occurring in patients with severe liver disease in the absence of any other underlying cause of renal disease. A decrease in blood flow to the kidneys has been suggested as the underlying pathophysiology.

Pay special attention to risk factors leading to development of HRS, including low sodium and high potassium levels in the serum, low plasma osmolarity, high urine osmolarity, and poor nutritional status. Avoid large-volume paracentesis without plasma volume replacement. ^[22]

Liver transplantation is the treatment of choice for HRS; however, some patients continue to require dialysis following the transplant.

Peritoneal dialysis, hemodialysis, and hemofiltration have limited benefit and, thus, remain controversial in HRS. Systemic vasoconstricting agents and renal vasodilators are used but have limited value. Medical therapy is considered a temporary measure to improve renal function while the child with HRS is waiting for liver transplantation. Vasoconstrictors, such as the vasopressin analog terlipressin, have shown promising results in adult patients with HRS. Terlipressin administration results in splanchnic vasoconstriction and thus an increase in systemic and renal perfusion in HRS. Therapy with terlipressin constitutes a bridge towards liver transplantation and improves the prognosis after transplantation.

Cerebral edema occurs in as many as 80% of patients. It increases intracranial pressure (ICP), resulting in impaired cerebral perfusion. This can result in irreversible neurologic damage, and death. Cytotoxic and vasogenic edema are present, presumably caused by release of neurotoxins in the circulation.

Insertion of an ICP monitor in patients with grade 3 encephalopathy is advisable to detect cerebral edema early in its course.

Preventive measures include positioning the patient with the head elevated and avoidance of any manipulations that increase ICP. Other preventive measures are the avoidance of hypothermia and hypercapnia, controlling agitation, and instituting moderate hyperventilation.

Continuously monitoring ICP in severe illness is of vital importance, especially in stage 3 or 4 of hepatic encephalopathy. Mannitol is used in patients with documented ICP greater than 30 mm Hg and is considered in patients with progressive edema.

Bacterial and fungal infections commonly occur. Use appropriate antibiotics to treat serious infections, septicemia, peritonitis, urinary tract infections, and pneumonia.

Use lactulose enemas to evacuate the bowel. Oral neomycin is indicated to decrease enteric bacteria that produce ammonia.

Orthotopic liver transplantation (OLT) remains the only effective mode of treatment of FHF. FHF is the indication for 11-13% of liver transplantations and carries an important prognostic implication. Consider OLT in any patient presenting with FHF, regardless of the etiology. ^[23] Consider urgent transplant when the international normalized ratio (INR) reaches 4, especially in very young children. ^{[24, 25]}

A more recent approach is to try using liver-assist devices, such as matrices of cultured hepatocytes, to support the patient’s liver until hepatic regeneration occurs or a suitable donor is made available for liver transplantation. ^{[26, 27]}

In an acute emergency, segment liver transplant or living related donor transplant is performed to spare the child with FHF the potentially fatal outcome of rapidly progressive liver necrosis. Innovative approaches, such as auxiliary hepatic transplantation, ^{[28, 29]} xenograft, extracorporeal human liver, and artificial liver support devices, also are considered in emergency situations. 

Despite technical difficulties and a donor organ shortage, the results of OLT in the pediatric age group with end-stage liver disease have demonstrated promising results. Therefore, early referral to a specialized center for liver transplantation is vital. ^{[27, 7]}

See Pediatric Liver Transplantation and Liver Transplants for more complete information on these topics.

Special attention to diet is indicated. Patients require high calories, high carbohydrates, and moderate fat. Total parenteral nutrition (TPN) may be needed to ensure adequate nutrition, especially when enteral feeding is not possible. Special formulas are available that are high in branched-chain amino acids and low in aromatic amino acids and electrolytes.

Consultations with the following specialists may be indicated:

• Gastroenterologist

• Neurosurgeon

• Hematologist

• Infectious disease specialist

• Transplantation surgeon