This document provides information about acute liver failure in children. It defines acute liver failure as resulting from massive liver cell death or impairment within 8 weeks without pre-existing liver disease. Causes include viral hepatitis, drugs/toxins, metabolic disorders. Clinical features include jaundice, encephalopathy. Management involves supportive care, treating the cause, and preparing for transplant if needed to prevent complications and allow the liver time to regenerate.

1. ACUTE LIVER FAILURE IN CHILDREN
DR.VIDEESH GUIDED BY
DNB TRAINEE DR.ANITA
M.D (PAEDS)

2. INTRODUCTION
 Acute liver failure (ALF) is a clinical syndrome resulting
from massive necrosis or from severe functional
impairment of hepatocytes.
 Functions including:
 Synthetic
 Excretory
 Detoxification
all are severely impaired.

3. DEFINITION The original definition of fulminant hepatic failure as
coined by Trey and Davidson in 1970 stipulated an
onset of hepatic encephalopathy within 8 weeks of the
first symptoms of illness, in patients without pre-
existing liver disease.
 The recognition that different clinical patterns of acute
liver failure related to aetiology and prognosis, has led
to revision of this definition and the development of
differerent classifications.

4. O`GRADY et al proposed three subcategories of ALF
TYPE INTERVAL CEREBRAL
EDEMA
PROGNOSIS CAUSES
HYPERACUTE <7 days common moderate Hep A,B
Acetaminoph
en
ACUTE 8-28 days common poor Non-A/B/C,
drugs
SUBACUTE 29days-24
wks
rare poor Non-A/B/C,
drugs

5. • Biochemical evidence of acute liver injury of <8wks
duration
• No evidenvce of chronic liver disease
• PT>15sec or INR>1.5 not corrected by Vit K in the
presence of clinical hepatic encephalopathy
• PT>20sec or INR>2 regardless of encephalopathy.
The currently accepted definition includes:

6. EPIDEMIOLOGY
 The true incidence of ALF in children is
not known
 It is estimated that 0.2%-1% of all acute
hepatitis can progress to liver failure.

7. ETIOLOGY :
In about half to two-third of patients with ALF
etiology is unknown.
INFECTIVE
• Hepatitis virus A, B, C, D, E
• Herpes simplex
• Epstein Barr virus
• Parvovirus B19
• Varicella zoster
• CMV
• Adenovirus
• Echovirus
• Coxsackie virus

8. A
DRUG REACTIONS AND TOXINS
• Acetaminophen (paracetamol) overdose
• Halothane
• Isoniazid
• Sodium Valproate
• Phenytoin
• Herbal remedies
• Ecstasy(Methylene Dioxymetamphetamine)

9. AMETABOLIC
• Wilson’s diseaseA
• Neonatal hemochromatosis
• Tyrosinemia type 1
• Mitochondrial disorders
• Hereditary fructose intolerance
• Alpha-1 antitrypsin deficiency
• Niemann-pick disease
• Indian childhood cirrhosis
• Glycogen storage disease type 4
• Urea cycle defect

10. ISCHAEMIC
• Budd–Chiari syndrome
• Venoocclusive disease
• Right sided congestive heart failure
• Cardiogenic shock

11. MISCELLANEOUS
• Massive malignant infiltration
• Severe bacterial sepsis
• Heat stroke
• Autoimmune hepatitis
• Viral infection on underlying chronic liver disease.

12.  In India, the etiological proportions are seen as
HAV infection(35%),HEV(15%), Mixed
HAV,HEV (15%) and HBV(10%),non A to
E(15%) and Drug induced (5%).
 If appropriate testing is not done hepatitis B
may not be diagnosed since one-third to one-
half of acute liver failure become seronegative
for hepatitis B surface antigen (HBsAg) after a
few days.

13.  Superinfection of hepatitis B with delta
virus causes ALF in 50% of cases.
 Reactivation of hepatitis B or C virus
may lead to ALF following antitumour
chemotherapy or cessation of
immunosuppressive therapy.

14.  Massive infiltration of the liver as in a lymphoma
can lead to ALF
 Wilson’s disease must always be excluded in any
patient who is less than 35 years old, particularly if
haemolysis is associated.ALF can be due to
superimposed acute viral infection.

15. PATHOLOGY
 Patchy or confluent massive necrosis of hepatocytes is
seen on liver biopsy.
 Multilobular or bridging necrosis with collapse of the
reticulin framework of the liver occurs.
 There may be little or no regeneration of hepatocytes
 Centrilobular pattern of necrosis :
• Acetaminophen hepatotoxicity
• Circulatory shock

16.  Microvesicular fatty infiltrate of
hepatocytes :
• Reye’s syndrome,
• β-oxidation defects,
• Tetracycline toxicity

19. NECROSIS OF HEPATOCYTES

20. PATHOGENESIS
 About 1-2% of patients with viral hepatitis experience
ALF.
 Massive destruction of hepatocytes is due to:
• Cytotoxic effect of the virus,
• Immune response to the viral antigen.
 Hepatotoxic metabolites bonding covalently to
macromolecular cell constituents occurs in:
• Acetaminophen,
• Isoniazid.

21.  Fulminant hepatic failure may follow depletion of
intracellular substrates involved in detoxification,
particularly glutathione.
 Factors contributing to the pathogenesis include :
• Impaired hepatocyte regeneration,
• Altered parenchymal perfusion,
• Endotoxemia,
• Decreased hepatic reticuloendothelial function.

22.  The pathogenesis of hepatic encephalopathy relates to:
• Increased serum levels of ammonia
• False neurotransmitters, amines
• Increased γ-aminobutyric acid receptor activity
• Increased circulating levels of endogenous
benzodiazepine-like compounds

23. CLINICAL FEATURES
Initially prodromal symptoms include:
• Low grade fever
• Abdominal pain
• Anorexia
• Vomiting
These symptoms are followed by
• Progressive jaundice
• Fetor hepaticus
 A rapid decrease in liver size without clinical
improvement is an ominous sign.
 A hemorrhagic diathesis and ascites can also develop

24.  Patients with hepatic encephalopathy initially have minor
disturbances of consciousness or motor function.
 Irritability, poor feeding, and a change in sleep rhythm may be
the only findings in infants.
 Asterixis may be demonstrable in older children.
 Patients are often somnolent or confused or combative on
arousal and eventually may become responsive only to painful
stimuli.

25.  Patients may rapidly progress to deeper stages of
coma that include:
• Extensor responses
• Decerebrate
• Decorticate posturing
 Respirations are usually increased early, but
respiratory failure may occur in stage IV coma

26. STAGES I II III IV
Symptoms Periods of lethargy,
euphoria, reversal
of day-night
sleeping, may be
alert
Drowsiness,
inappropriate
behaviour,
agitation, wide
mood
swings,
disorientation
Stupor but
arousable,
confused,
incoherent
speech
Coma
IVa responds to
noxious stimuli
IVb no
response
Signs Trouble drawing
figures, performing
mental tasks
Asterixis, fetor
hepaticus,
Incontinence
Asterixis,
hyperreflexia,
extensor
reflexes,
rigidity
Areflexia, no
asterixis,
flaccidity
Electroencep
halogram
Normal Generalized
slowing, q
waves
Markedly
abnormal,
triphasic
waves
Markedly
abnormal
bilateral
slowing,
d waves,
electric-cortical
STAGES OF HEPATIC ENCEPHALOPATHY

27. ACUTE LIVER FAILURE :
MANAGEMENT

28. Acute liver failure is a medical emergency , often
associated with unpredictable and sometimes fatal
outcome.
Recovery occurs if liver gets adequate time to
regenerate with supportive therapy.
Every child with ALF must be treated in ICU
setting preferably with liver transplant facility.

29. AIMS OF THE THERAPY
To prevent & manage complications,
To access the etiology & treat accordingly,
Preparing the patient for liver
transplantation if lack of spontaneous
recovery by intensive supportive care.

30. INITIAL WORKUP &
INVESTIGATIONS
GENERAL :
• Complete blood count
• Liver function tests
• Ammonia levels
• PT , INR
• Blood sugar level
• Electrolytes
• RFT
• Urine analysis
• Blood culture
• Blood gas and acid-base parameters
• Blood grouping-cross match
• X-ray chest

31. VIRAL HEPATITIS MARKERS :
• HAV IgM Antibody
• HEV IgM Antibody
• HBsAg
• Anti HBc IgM Antibody
• HBV DNA
Store sera prior to administration of any blood
products for further investigations if needed

32. IN PRESENCE OF SEVERE
HEMOLYSIS OR SEVERE ANEMIA
• Malaria parasite, malaria antigen
• G6PD level estimation
• Ceruloplasmin, urine copper
• Leptospira antibody
Liver biopsy has no role in ALF

33. IN SELECTED PATIENTS :
• Autoimmune markers (Coombs test, antinuclear
antibody, liver kidney microsomal antibody (LKM), smooth
muscle antibody)
• Ceruloplasmin, urinary copper
• Paracetamol level, Sodium valproate level
• Urine succinylacetone

34. GENERAL PRINCIPLES OF CARE AND
MONITORING PROTOCOL
• Ensure complete asepsis
• Establish adequate IV access (CVP line)
• Continous monitoring of vital signs
• Pulse oximetry
• Neurological/ coma grading every two hrly
• Blood sugar estimation 2-6 hrly as needed

35. • Electrolytes, ABG, PT, LFT, RFT 12-24
hrly
• CBC, Blood culture, ESR, urine culture,
CRP, x-ray chest 24-72 hrly
• Nasogastric tube for feeding/ drainage
• Urinary cathetre
• Care of bowel, bladder, back, skin, eyes

36. STANDARD PROTOCOL FOR
MANAGEMENT OF ALF
• Raise head end (30°-45°) and maintain head in
neutral position
• Inj. Cefotaxim and Cloxacillin
• IV Fluids N/5 saline in 10% dextrose at 2/3rd of
maintenance after initial fluid resuscitation
• KCl to be added as per serum potassium level.

37. • Lactulose through NG Tube.
• Mannitol 20% 3-5ml/kg/dose IV slow bolus 4-6
hrly for 6-8 doses (In grade 3-4 coma).
• Ranitidine IV 12 hrly.
• Inj. Vit K.
• Hepatic coma feeds.

38. CONDITIONS WITH SPECIFIC
THERAPY
No. Condition Therapy
01. Acetaminophen toxicity N-acetyl cysteine
02. Amanita poisoning Penicillin & silibinin
03. Herpes simplex Acyclovir
04. Malaria Antimalarials
05. Enteric encephalopathy Cefotaxim/ceftriaxone
06. Wilsons disease d-penicillamine
07. Tyrosinemia Nitisinone
08. Leptospirosis Penicillin, doxycycline,
tetracyclines
There is increasing evidence for use of N-acetyl cysteine
(NAC) infusion in all cases of ALF irrespective of the etiology
Dose : 100 mg/kg/day.

39. NUTRITION
• Catabolic stage characterised by increased negative
nitrogen balance & increased resting energy
expenditure.
• Enteral nutrition with higher caloric density feeds to
avoid excessive free water and hypo-osmolality.
• Normal protein intake in stage ii & iii
encephalopathy.
• Afterwards restriction of proteins.

40. FLUID AND ELECTROLYTE
DISTURBANCES
HYPOTENSION :
• Volume replacement with NS, RL, plasma or blood.
• Give 2/3rd maintenance fluid - N/5 saline in 10% dextrose.
• Avoid overloading.
• If MAP (DBP+1/3PP) is <60mmHg – Start Inotropes.
METABOLIC ACIDOSIS :
• Suspect fluid deficit.
• Look for sepsis (if no fluid deficit).

41. HYPOKALAEMIA :
• Can precipitate & worsen the severity of hepatic
encephalopathy.
• Associated with metabolic alkalosis.
• Give KCL infusion.
METABOLIC ALKALOSIS :
• Increase IV KCL to next step.

42. HYPONATREMIA :
• Restrict fluids to 2/3-3/4 maitenance.
• Restrict sodium infusion to <2mEq/kg/day.
HYPERNATREMIA :
• May be precipitated with lactulose administration
:reduce/stop lactulose.
• Give N/5 fluids including correction fluid.
HYPOGLYCEMIA :
• Infuse 50 % Dextrose @ 1ml/kg.
• Maintain blood sugar between 100-200mg/dl.

43. ANTIBIOTICS
Empirical administration of antibiotics is recommended where
Infection or impending risk of sepsis is high
• Surveillance cultures reveal significant isolates
• Progression of or advanced stage hepatic encephalopathy
• Refractory hypotension
• Presence of SIRS components
• Patients listed for OLT ( immunosupression )

44. PREVENTION OF GI HEMORRHAGE
• Secondary to gastritis, stress ulcers,
coagulopathy
• Inj. Vit K <1 yr -2.5mg/day
>1 yr -5mg/day
>5 yr -10mg/day
• IV ranitidine
• IV proton pump inhibitor

45. HEPATIC ENCEPHALOPATHY
• Reduce or stop protein in grade iii /iv
• Prefer vegetable proteins-BCAA
• Lactulose-0.5ml/kg/dose every 6 hrs orally
• Nonabsorbable oral antibiotics- Rifaximin
• Analgesia and judicious sedation- Propofol,
benzodiazepines

46. COMPLICATIONS OF MANAGEMENT

47. 01.RAISED INTRACRANIAL PRESSURE
Sustained rise of ICP >20 mmHg
C/F - Abnormally reacting pupils
- Increased muscular tone
- Decerebrate posturing
- Abnormal reflexes
- Focal seizures
- Loss of brainstem reflexes
- Bradycardia
- Increased B.P.
CEREBRAL EDEMA(B/W STAGE II&III ) HAS VERY POOR PROGNOSIS
& ALL EFFORTS SHOULD BE TAKEN TO PREVENT IT.

48. STRATEGIES TO PREVENT CEREBRAL
EDEMA
• Avoid excessive handling, suctioning, stimulation
• Prevent coughing, vomiting, frequent movements,
neck veins compression, fever, hypertension,
hypoxia
• Raise head end 30°. Avoid neck flexion
• Fluid restriction to 60-75% of maintenence with
good cerebral perfusion pressure
• Mannitol 20% 0.5gm/kg over 10-15min repeated
4-6hrly for max 72hr in mild to moderate
ICP(<60mmHg).

49. • In anuric or ARF patient dialysis with
mannitol
• Elective ventilation- hyperventilate to
maintain pCO2 bw 30-35mmHg
• Mannitol resistant CE- Sodium Thiopental
( bolus dose 24mg/kg over 15min f/b slow iv
infusion bw 1-2mg/kg/hr )
• Refractory ICP- Indomethacin 25mg infused
iv over 1min

50. 02.CONVULSIONS
• Phenytoin 10mg/kg iv slowly. Wait for 20 min. if
no response then repeat.
• Maintainence 5-8 mg/kg/day.
• If convulsions persist, Phenobarbitone 10-
15mg.kg slowly & wait for 20 min.
• Maintainence 5mg/kg/day in two doses
• If no response Thiopentone iv may be used but
watch for Hypotension.

51. 03.HEMORRHAGE
• If PT <30sec – FFP only for invasive procedures
• If PT >30sec – FFP 10ml/kg.
• Severe bleeding – FFP & Platelet transfusion.
• Significant hypofibrinogenemia
(<100mg/dl) - Cryoprecipitate
• Recombinant factor VIIa – when FFP has failed
to correct INR , volume overload, before
invasive procedures with high risk of bleeding.

52. 04.RENAL FAILURE
• Due to hepatorenal syndrome, dehydration, acute
tubular necrosis.
• Maintain urine o/p >1ml/kg/hr.
• Try colloid challenge 10ml/kg. repeat if no response.
• Diuretics.
• Renal replacement therapy- in fluid overload,
unresponsive renal failure, hyperkalemia.

53. 05.SEPSIS
• Signs- tachycardia, raised core-toe temp. gradient,
fall in BP or urine output, hypoglycaemia,
hypothermia, deterioration in mental state, fits,
acidosis.
• Common organisms- Staphylococci, Gram negative
bacteria,Fungal infections.
• Broad spectrum antibiotics - IV
Cloxacillin/Ampicillin + IV Cefotaxim/Ceftazidime.
• Antifungals/Metronidazole may be added if no
response in 48-72hrs.

54. LIVER TRANSPLANTATION
 LT is the only definitive treatment for ALF.

 Several prognostic scoring systems have been devised
to predict mortality and to identify those requiring
early LT.
 These include King’s College Hospital (KCH) criteria,
pediatric end-stage liver disease (PELD) score,
APACHE II, and Clichy criteria.
 The KCH criteria have been shown to have a better
performance than the Clichy criteria and is widely
used.

55.  Liver transplantation could be :
CADAVERIC
1)Whole graft – When the whole liver is used.
2)Spilt graft – When the donor liver is used for two
recipients.
3)Reduced graft – When the donor liver is reduced to
suit the size for recipient.
LIVING RELATED
When a live donor gives part of his/her liver to
recipient.

56. Contraindications for pediatric LT
 Active uncontrollable and untreatable
sepsis,
 Severe cardiopulmonary disease,
 Multi-organ failure,
 Extrahepatic malignancy,
 Mitochondrial disease,
 Active substance abuse,
 HE grade IV with severe neurological
impairment

57. Outcome :
 In more than 50% of children with ALF there is poor
survival unless LT is offered at the appropriate time.
 Poor Prognostic factors
- Liver necrosis
- Multi organ failure
- INR >4
- Young age of the child (<1 yr)
- Need for dialysis before LT
 The prognosis is better with hepatitis A,
acetaminophen overdose and ischemia (approximately
60% spontaneous survival), and
poor with drug-induced
ALF (non-acetaminophen), hepatitis B, and indeterminate
cases.

58. THANK YOU