ACUTE LIVER FAILURE IN

CHILDREN

BY: BHIRRINTA VARUGHESE

SUPERVISOR: DR SAKINAH
AZMI
 Functions of liver
Biosynthesis: albumin, globulins,
lipoproteins, etc.

Detoxification: endogenous and

exogenous compounds

Storage: fat soluble

vitamins and water soluble
as B12.

Secretion: water soluble

end products, bile salts,
etc

Metabolic regulation: plays a major role in

carbohydrates, lipids and protein metabolism.
INTRODUCTION

 Acute liver failure (ALF) in children is a

relatively rare clinical syndrome
 Mortality rate is high - 60 to 80%
 Etiologies vary by age with metabolic and
infectious diseases prominent in the first year
of life and acetaminophen overdose and
Wilson's disease occurring in adolescents.
 In almost 50% of cases, however, the child
has an indeterminate cause for acute hepatic
failure.
Definitions
 Fulminant hepatic failure (HF): hepatic dysfunction
(hepatic encephalopathy and coagulopathy) within 8
weeks of evidence of symptoms of liver disease and
absence of pre-existing liver disease in any form.

 Hyperacute/fulminant HF: encephalopathy within 2

weeks onset of jaundice

 Subfulminant HF: encephalopathy within 2-12 weeks

of onset of jaundice

 Subacute/ late onset HF: encephalopathy later than 8

weeks to 6 months of onset of symptoms.
Causes

 The cause of ALF remains indeterminate in 18

to 47% of cases, depending upon the
extension of the work up screening
 The most common causes in neonates and
infants are metabolic diseases, whereas viral
hepatitis and drug-induced ALF are
predominant in children
 Hepatitis A or E are the main causes of ALF in
countries where these viruses are endemic.
Differentials:

 Vascular?
 Infectious?
 Traumatic?
 Autoimmune?
 Metabolic?
 Idiopathic/iatrogenic?
 Neoplastic?
 Congenital?
Mechanism of hepatic injury

A hepatocyte is a cell of the main parenchymal tissue

of the liver. Hepatocytes make up 70-85% of the liver's
mass. These cells are involved in:

 Protein synthesis
 Protein storage
 Transformation of carbohydrates
 Synthesis of cholesterol, bile salts and phospholipids
 Detoxification, modification, and excretion of
exogenous and endogenous substances
 Initiation of formation and secretion of bile
Mechanism of hepatic injury

1. Immuned-mediated hepatocellular injury

 Viral infections, drug hepatotoxicity
2. Direct hepatocellular injury
 Hepatotrophic virus family – HAV, HBV, HCV
 Toxic or reactive metabolites
 Toxic metabolites of compounds-metabolic
disease
3. Ischemic hepatocellular injury
 Shock state
Metabolic
 Tyrosinemia is caused by a defect in tyrosine degradation
pathway; the body cannot break down the amino acid
tyrosine. Liver failure, ascites and edema with onset in the
first weeks or months of life are common.
• Tx: low protein diet may be required.

 Galactosemia is an autosomal recessive disorder of

carbohydrate metabolism caused by a severe deficiency of
the enzyme galactose-1-phosphate uridyltransferase
(GALT).
• Unable to metabolize galactose properly.
• the affected infants develop a severe condition with multiorgan
involvement, including liver failure. Hypoglycemia is a feature of
galactosemia.
• Tx: eliminating lactose and galactose from the diet. Eg: honey,
beets, cheese, yogurt, cherries, celery, kiwifruit, soy sauce, plums,
and dried figs.
Neonatal Haemochromatosis
 iron deposition causes damage to the liver and
other organs and tissues.
 Causes still unkown, however research suggest it is
an alloimmune disease.
 Researchers believe most cases of neonatal
hemochromatosis result from maternal fetal
alloimmunity, a condition in which antibodies from
the mother travel over the placenta and mistakenly
attack the fetus.
 Antenatal manifestations include growth
restriction, prematurity, hydrops fetalis,
oligohydramnios, fetal hepatomegaly, and ascites.
Wilson's disease
 Autosomal recessive disorder; copper
builds up in body.
 Due to mutation in the Wilson disease
protein (ATP7B)
 Wilson's disease is typically treated with:
• Dietary changes involve eating a low copper
diet and not using copper cookware.
• Medications used include chelating
agents such as trientine and d-penicillamine.
Acetaminophen toxicity
 Acute toxicity dose >150mg/kg within a 24 hours
period in < 12 years of age. Fatality is unlikely if <
225mg/kg ingested.
 Patient with acetaminophen-induced acute
hepatic failure have a higher rate of spontaneous
recovery than do patient with viral hepatitis
 Liver damage results not from paracetamol itself,
but from one of its metabolites, N-acetyl-p-
benzoquinone imine (NAPQI). NAPQI decreases
the liver's glutathione and directly damages cells
in the liver.
 NAC serves as precursor to facilitate
synthesis of glutathione
 Initiation of N-ACETYLCYSTEINE within
10 H of ingestion but still beneficial up to
24 H of ingestion (serves as precursor to
facilitate synthesis of glutathione)
 Dose: 150mg/kg in 3mls/kg 5% Dextrose over 15 min,
• followed by 50mg/kg in 7mls/kg 5% Dextrose over 4
hours,
• then 100mg/kg in 14mls/kg 5% Dextrose over 16
hours.
 Refer Paeds Protocol page 553.
Clinical presentations
 In the newborn, symptoms are nonspecific, sometimes only
related to an altered general condition, failure to thrive, and
vomiting. Signs of hepatic encephalopathy are not specific
and may be limited to behavioral changes, preceding the
onset of coma.
 In infants or older children, there is usually a prodromic
phase of malaise, nausea, and anorexia and then jaundice
develops subsequently.
 Hemorrhage may occur spontaneously, and involves mainly
the digestive tract.
 Severe hypoglycemia, that may lead to seizures. Hepatic
encephalopathy may be absent in spite of severe liver
dysfunction or develop within a few hours to days or weeks
from onset of liver failure.
 In older children, signs and symptoms are identical to those
in adults but the classical symptoms of asterixis, tremors,
and fetor hepaticus are often absent
History

 Duration of illness, onset of jaundice and

encephalopathy
 Risk factors for hepatitis eg. Street food,
sanitation
 Drugs and immunization hx
 Family hx and consanguinity
 H/o bleeding episode
 Features of hepatic encephalopathy
 Physical examination

 Jaundice
 Anaemia
 Vital sign - hypotension, tachycardia,
tachypnoea
 Mental status
 Hepatosplenomegaly
 Stigmata of chronic liver disease
 Features of raised ICP
 Nervous system examination
Salient features

 Jaundice with impalpable liver or liver of

reducing size
 Encephalopathy - may worsen rapidly
 Bruising, petechiae or bleeding from
deranged clotting unresponsive to vitamin k
 Failure to maintain normoglycaemia or
presence of hyperammonaemia
 Increase intracranial pressure
Hepatic encephalopathy

 Hepatic encephalopathy is a syndrome in

patients with cirrhosis.
 Hepatic encephalopathy is defined as a
spectrum of neuropsychiatric abnormalities
in patients with liver dysfunction, after
exclusion of brain disease.
 Characterized by personality changes,
intellectual impairment, and a depressed
level of consciousness.
 Investigations

 FBC - leucocytosis, thrombocytopenia

 LFT
 RP
 Serum ammonia
 Serum calcium, magnesium, phosphate
 Serum lactate
 Coagulation profile
 Blood gas
 Blood c+s, urine c+s
Investigations (to detect
causes)
 Serological markers
 Anti HAV IgM
 HbsAg, AntiHBCIgM
 Anti HEV IgM
 Screening for other virus - HSV, CMV etc
 Immunological test
 Liver biopsy - in autoimmune, metabolic
causes of liver failure
Screening for Wilson's
disease
 Eye examination for kayser-fleischer ring and
cataract
 Serum copper
 Serum ceruloplasmin
 24 H urine copper
Complications of ALF in children

1. Energy production deficiency

 Impaired glycogen storage and a diminished ability for
gluconeogenesis.

2. Coagulopathy
 Productions of clotting factors are reduced.
 Correcting coagulopathy by transfusion of fresh frozen plasma (FFP),
platelets, cryoprecipitate, and packed red blood cells.

3. Hepatic encephalopathy
 Liver's ability to metabolize ammonia is reduced and lead to
hyperammonemia which is associated with the development of
encephalopathy and cerebral edema.

4. Cerebral edema
Management (1/3)
-mostly supportive
-refer paed protocol pg 386

 Nurse in quiet darkened room with head-end

elevated at 20° with no neck flexion
 Do not sedate unless already ventilated
 Maintain blood glucose between 6-9 mmol/L using
minimal fluid volume (40-60 ml/kg/day crystalloids)
with high dextrose concentration
 Check capillary blood sugar every 2-4 hourly
 Strict monitoring of urine output and fluid balance
 Check urinary electrolytes, serum urea, creatinine,
electrolytes, osmolarity
 Frequent neurological observation
Management (2/3)

 Maintain oxygenation
 Give vitamin k to correct prolonged PT. If
frank bleeding (GIT/oral) occurs, consider use
of FFP or IV Cryoprecipitate at 10ml/kg
 Prophylactic Ranitidine + oral antacid to
prevent gastric/duodenal ulceration
 Full septic screening on admission, CXR. Treat
sepsis aggressively, monitoring levels of
aminoglycosides frequently.
Management (3/3)

 Stop oral protein initially and gradually reintroduce

 Give lactulose
 Strict fluid balance
 Consider N-Acetylcysteine – if due to paracetamol
toxicity
 Antibiotic - cover for gram negative organisms and
anaerobes
 Antiviral - acyclovir (recommended in neonates and
small infants due to possible AHF 2° to HSV infection
 If renal dysfunction - consider haemofiltration if
supportive measure fail
Thank You!