Chapter 364

Fulminant Hepatic
Failure
Fulminant Hepatic Failure
acute liver failure
clinical syndrome resulting from

massive necrosis of hepatocytes or

from severe functional impairment of
hepatocytes.
Synthetic, excretory, and detoxifying

functions of the liver are all severely

impaired.
Fulminant Hepatic Failure
ADULTS: hepatic encephalopathy has been
an essential diagnostic feature.
CHILDREN: includes the ff:

biochemical evidence of acute liver injury (usually

<8 wk duration)
no evidence of chronic liver disease;
and hepatic-based coagulopathy
(PT >15 sec or INR >1.5 not corrected by vitamin K in
the presence of clinical hepatic encephalopathy, or
a PT >20 sec or INR >2 regardless of the presence of
clinical hepatic encephalopathy.
 Liver failure in the perinatal period can be
associated with prenatal liver injury and
even cirrhosis.

Examples:
neonatal iron storage (hemochromatosis) disease
tyrosinemia,
some cases of congenital viral infection.
 Liver disease may be noticed at birth or after
several days of apparent well-being.
Fulminant Wilson disease:
occurs in older children who were previously
asymptomatic,
have preexisting liver disease
In some cases of liver failure, particularly in the
idiopathic form of acute hepatic failure, the onset of
encephalopathy occurs later, from 8-28 wk after the
onset of jaundice.
Etiology
complication of viral hepatitis (A, B, D, E).
combined infections with the hepatitis B

virus (HBV) and hepatitis D.

Fulminant hepatic failure can also be

caused by autoimmune hepatitis in

approximately 5% of cases.
positive autoimmune marker (e.g., antinuclear
antibody, antismooth muscle antibody, liver-
kidney microsomal antibody, or soluble liver
antigen)
an elevated serum immunoglobulin G level.
Etiology
idiopathic form of fulminant hepatic failure
accounts for 40-50% of cases in children.
Ischemia and hypoxia
Various hepatotoxic drugs and chemicals

carbon tetrachloride
Amanita phalloides mushroom
acetaminophen overdose. (most common etiology
of acute hepatic failure in children and
adolescents in the United States and England)
Etiology
Metabolic disorders:
Wilson disease
acute fatty liver of pregnancy
galactosemia
hereditary tyrosinemia hereditary fructose
intolerance
neonatal iron storage disease
defects in -oxidation of fatty acids,
deficiencies of mitochondrial electron transport
particularly mitochondrial DNA depletion disorders
Etiology
hemophagocytic lymphohistiocytosis
caused by several gene defects
infections by mostly viruses of the herpes

group
organ transplantation
malignancies.
Pathology
Liver biopsy
patchy or confluent massive necrosis of
hepatocytes.
Multilobular or bridging necrosis = collapse of the
reticulin framework of the liver.
zonal pattern of necrosis may be observed with
certain insults.
Evidence of severe hepatocyte dysfunction rather
than cell necrosis is occasionally the predominant
histologic finding
Pathogenesis
poorly understood.
It is unknown why only approximately 1-2% of patients
with viral hepatitis experience liver failure.
Massive destruction of hepatocytes might
represent both a direct cytotoxic effect of the virus
and an immune response to the viral antigens.
Hepatic encephalopathy can relate to:
increased serum levels of ammonia
false neurotransmittersamines
increased -aminobutyric acid receptor activity
increased circulating levels of endogenous benzodiazepine-like
compounds
Decreased hepatic clearance of these -> central nervous system
dysfunction.
Clinical Manifestations
(+) history of developmental delay and/or
neuromuscular dysfunction can indicate an underlying
mitochondrial or -oxidation defect.
usually been previously healthy and most often has no
risk factors for liver disease such as exposure to toxins
or blood products.
COMMON S/Sx
Progressive jaundice
fetor hepaticus
Fever
anorexia
vomiting,
abdominal pain
Clinical Manifestations
 rapid decrease in liver size without clinical
improvement is an ominous sign.
hemorrhagic diathesis and ascites can

develop.
closely observed for hepatic encephalopathy,

initially characterized by:

minor disturbances of consciousness or motor function
INFANTS: Irritability, poor feeding, and a change in
sleep rhythm
OLDER CHILDREN: asterixis
Laboratory Findings
Serum direct and indirect bilirubin levels and serum
aminotransferase activities may be markedly elevated.
Serum aminotransferase activities do not correlate well

with the severity of the illness and can actually decrease

as a patient deteriorates.
blood ammonia concentration is usually increased, but

hepatic coma can occur in patients with a normal blood

ammonia level.
PT and the INR prolonged (do not improve a er

parenteral administration of vitamin K)

Hypoglycemia (infants).
Hypokalemia, hyponatremia, metabolic acidosis, or

respiratory alkalosis
Treatment
Specific therapies for identifiable causes of
acute liver failure include:
N-acetylcysteine (acetaminophen),
acyclovir (herpes simplex virus), penicillin (Amanita
mushrooms),
nucleos(t)ide analogs such as ente- cavir or lamivudine
(HBV),
prednisone (autoimmune hepatitis)..
Management of other types of fulminant
hepatic failure is supportive. No therapy is
known to reverse hepatocyte injury or to
promote hepatic regeneration
Treatment
liver transplantation if necessary and managed in
an intensive care unit with continuous monitoring
of vital functions.
Endotracheal intubation

prevent aspiration, to reduce cerebral edema by

hyperventilation, and to facilitate pulmonary toilet
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.
 Hypovolemia: treated with cautious infusions of isotonic fluids and
blood products.
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: Parenteral supplementation with IVF, calcium,

phosphorus, and magnesium may be required.

Coagulopathy

should be treated with parenteral administration of vitamin K

can require infusion of fresh-frozen plasma, cryoprecipitate, and platelets
Recombinant factor VIIa: transient correction of coagulopathy
refractory to fresh frozen plasma infusions and can facilitate the
performance of invasive procedures
Plasmapheresis: temporary correction of the bleeding diathesis

without resulting in volume overload.

Treatment
placement of a central line or an
intracranial pressure monitor.
Continuous hemofiltration is useful for

managing fluid overload and acute renal

failure.
monitored closely for infection, including

sepsis, pneumonia, peritonitis, and urinary

tract infections.
 Protein intake should be initially restricted or eliminated, depending
on the degree of enceph lopathy.
LACTULOSE:
should be purged with several enemas.
Lactulose should be given every 2-4 hr orally or by nasogastric tube in doses
(10-50 mL) suffcient to cause diarrhea.
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.
rifaximin or neomycin
can reduce enteric bacteria responsible for ammonia pr duction.
Oral antibiotics may be more effective than lactulose in lowering serum
ammonia levels.
 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 main- taining cerebral perfusion pressure, and in

establishing the suitability of a patient for liver transplantation.
Temporary liver support

Nonbiologic systems, essentially a form of liver dialysis with an

albumin-containing dialysate, and biologic liver support devices
improve serum biochemical abnormalities, neurologic function,
little evidence of improved survival, and few children have been treated.

Orthotopic liver transplantation

can be lifesaving in patients who reach advanced stages (III, IV) of hepatic
coma.
Prognosis
Children with acute hepatic failure fare better than
adults.
Improved survival can be attributed to careful

intensive care and if necessary liver transplantation.

In patients who progress to stage IV coma, the

prognosis is extremely poor.

Brainstem herniation is the most common cause of

death.
Major complications such as sepsis, severe

hemorrhage, or renal failure increase the mortality.

e prognosis is particularly poor in patients with liver
necrosis and multiorgan failure.
Prognosis
Age <1 yr, stage 4 encephalopathy, an INR
>4, and the need for dialysis before
transplantation associated with increased
mortality.
Pretransplantation serum bilirubin

concentration or the height of hepatic

enzymes is not predictive of
posttransplantation survival.
plasma ammonia concentration >200 mol/L

is associated with a 5-fold increased risk of

death.
Prognosis
Children with acute hepatic failure are more likely to
die while on the waiting list compared to children with
other diagnoses.
6 mo postliver transplantation survival of

approximately 75% in most studies is significantly

lower than the 90% achieved in children with chronic
liver disease.
Patients who recover from fulminant hepatic failure

with only supportive care do not usually develop

cirrhosis or chronic liver disease.
Aplastic anemia occurs in approximately 10% of

children with the idiopathic form of fulminant hepatic

failure and is o en fatal.