4. Acute liver failure: Definition
Acute liver failure in children includes
(1)Biochemical evidence of acute liver (usually <8 wks
duration)
(2) no evidence of a known chronic liver disease;
(3)hepatic-based coagulopathy that is not corrected by
parenteral administration of vitamin K;
(4) hepatic encephalopathy must be present if the
uncorrected prothrombin time (PT) is ≥ 15 seconds or
international normalized ratio (INR) is1.5 to 1.9,
respectively; and
(5) hepatic encephalopathy is not required if the PT
is ≥ 20 seconds or INR ≥2.0, respectively.
Squires et al.J Pediatr 2006;148:652–658
5. Acute Hepatic Failure: Background
Acute hepatic failure in children is a relatively rare
clinical syndrome
Mortality rate is high – 60 to 80%.
Among the different causes,
In western countries:
Viral cause – 12%
Drugs & Chemicals – 52%
Miscellaneous – 18%
Mixed: 10-22%
But in south-east Asia hepatitis is the most
predominant cause of ALF (50-70%)
6. Epidemiology
The incidence of fulminant hepatic failure appears to
be low in the United States, with approximately 2000
cases annually. Drug-related hepatotoxicity accounts
for more than 50% of acute liver failure cases,
including acetaminophen toxicity (42%) and
idiosyncratic drug reactions (12%). Nearly 15% of
cases remain of indeterminate etiology.
7.
8. Etiology of ALF In different age group
Neonates Infants
Infection
Inborn errors of
metabolism
Immune mediated
Ischemia
& abnormal
Perfusion
Drugs & toxins
other
HSV, Adeno virus
HBV
Galatosemia, tyrosinaemia,
Hereditary fructose
Intolerance.
Neonatal
Hemochromatosis
Congestive heart failure,
severe aspyxia
Hemophagocytic syndrome
HAV, HBV, HSV
hereditary fructose
Intolerance, others.
Auloimmune hepatitis
Congestive heart
Failure,
Acetaminophen,INH,
valproate malignancy
14. Acute liver Failure in neonate
The highest incidence of acute liver failure is
seen in newborns.
Dhawan et al, Clinics and Research in Hepatology and Gastroenterology
(2012) 36, 278—283.
Viral infections
HSV infection most common.
Infection acquired usually during perinatal
period.
HSV induced ALF carries high mortality & is
rarely accompanied by skin lesions.
15. It should be considered in all sick babies with
coagulopathy and raised transaminases.
Usually presented with poor feeding, lethargy,
coagulopathy within 2wks after birth.
Acyclovir should be started in all neonates with liver
failure, as herpes virus infection is the predominant
viral cause.
Dhawan et al, Clinics and Research in Hepatology and Gastroenterology
(2012) 36, 278—283.
16. Cont….
Metabolic disease:
Most common metabolic diseases that may
presented as neonatal ALF are:
Galactosemia, hereditary fructose intolerance,
Tyrosinaemia, neonatal iron storage disease.
Ischemic injury:
Due to hypovolaemia/hypotension, congestive
cardiac failure.
17. Viral causes are:
Hepatitis A,B,C,D,E: also may present as ALF
Hepatitis C: rare in children.
Dengue causes ALF in children in thailand.(40
cases with 66% mortality)
Poovorawan Y et al. Dengue virus infection: a major cause
of AHF in Thai children. Ann Trop Paediatr 2006, 26:17-23.
Other virus-CMV,HSV, EBV, Influenzae type A.
18. Non viral cause-rare
Severe sepsis
Bacterial infections- Salmonella,
Shigella, E.coli etc
Miliary TB
Leptospirosis
Plasmodium falciparum infection
19. Hepatitis
Direct cytopathic immune-mediated injury
necrosis in the centri-lobular areas
diffuse kupffer cell hyperplasia and
parenchymal collapse fulminant hepatic
failure
20. Important drugs responsible for ALF
•Dose dependant:
Acetamenophen
CCI
Mushroom
•Idiosyncratic:
INH
Valproic acid
Phenytoin
Carbamazepine
Propylthiouracil
Halothane
Nitrofurantoin
22. Most imp. drug of dose dependant toxicity.
Acute toxic Dose:
> 200 mg/kg within a 24 hour period in <12
yrs of age.
Patient with acetamenophen induced ALF
have a higher rate of spontaneous recovery
than do pt. with viral hepatitis.
25. Wilson disease
It is an autosomal recessive disorder.
The condition is due to mutations in the Wilson
disease protein (ATP7B) gene
May present as ALF in older child.
ALF due to wilson disease should be suspected in any
pt with.
-ALF + Coomb’s negative hemolytic anemia.
26.
27.
28. History
Duration of illness.Onset of jaundice and
encephalopathy.
Risk factors for hepatitis: eg- street food,
sanitation, BT, surgery.
Drug & immunization history
Family history and consanguinity
H/O any bleeding episode.
Systemic enquiry
Features of hepatic encephalopathy
29. Stages of encephalopathy
Encephalopathy Symptoms Signs
Stage I (mild)
Stage II
Stage III
Stage IV
Alert, euphoric, occasionally depression.
Poor concentration,
slow mentation and affect,reversed
sleep rhythm.
Drowsiness, lethargic, inappropriate
behavior, disorientation
Stuporous but easily arousable, marked
confusion, incoherent speech
Coma, unresponsive but may respond to
painful stimulus.
Trouble drawing figures,
performing mental task,
EEG-normal
Asterexis,fetor
hepaticus,EEG slowing of
wave.
Asterexis, hyperreflexia,
rigidity, EEG-Triphasic
wave
Planter extensor,
Rigidity ,Areflexia,
Flacidity.EEG-delta wave.
30. Aggravating factors of HE
GI bleeding
Hypovolemia
Hypokalemia
Hypoglycemia
Sedatives
Uremia
Sepsis
High protein diet
Constipation
Paracentesis
31. Physical examination
Jaundice
Anaemia
Vital signs: Hypotension, tachycardia, tachypnoea.
Mental status.
Hepatomegaly
Spleenomegaly
Stigmata of chronic liver disease.
Ascities
Features of raised ICP
Nervous system examination.
32.
33. Investigation
a. Complete blood count: Leucocytosis ,
thrombocytopenia
b. LFT: S. bilirubin
ALT: raised
AST :raised
Alkaline phospatase: may be normal or
PT and INR: to see the severiry of coagulopathy
and to asses prognosis.
c. Blood grouping and cross matching
d. C/S blood, urine etc.
34. Inv.continued
E . Biochemical test:
S. Electrolytes- Hypokalaemia and others.
S. Glucose- Hypoglycaemia.
S. Creatinine
S. Ammonia-
S. Calcium , Phosphate, Magnesium
S. lactate: At 4 hours(>3.5) or at 12 hours(>3)
are early predictors of outcome in
acetamenophan induced ALF.
F . Blood gas analysis.
35. To detect cause
G . Serological marker
Anti HAV IgM
HBsAg, AntiHBcIgM
Anti HEV IgM
Screening for other viruses- HSV, CMV etc.
36. Immunological test
S. immunoglobulin, ANA, anti SMA,
antiLKM1
J . S acetamenophen level
K . USG of HBS
L . Screening for metabolic disease.
M . EEG
N . Liver biopsy :in auto-immune, metabolic
causes of liver failure.
37. Screening for Wilsons disease
Eye examination for KF ring & cataract
S.copper
S. Ceruloplasmin
24 hours urinary copper
38.
39. Management of ALF
Medical: To maintain physiological functions of liver
Supportive care
Specific treatment
Surgical:
Extracorporeal systems
Liver transplantation
40. Supportive care.
Nursing in a quiet environment.
ICU.
Avoid sedation and stimulation.
Fluid restriction- 60-80% of daily requirement.
Choice of fluid: 0.225% Nacl in 10% dextrose.
Prevention of hypoglycemia(maintain glucose level
>4 mmol/L).
41. IV H2 blocker or PPI.
Antibiotic: Cefuroxim, amoxycillin, fluconazole.
(King’s College protocol)
Cefotaxime+ flucoxacillin-Indian protocol.
Anaemia should be corrected to ensure maximum
oxygen supply to tissue.
Lactulose
Management of complication:
42. Close Monitoring
Continous O2 saturation
Clinical status: Pulse & BP hourly, liver size 12 hrly
Strict input-output chart : Avoid fluid overload
CVP, Foley’s and arterial line : MAP >60 mmHg
Frequent evaluation of blood glucose and
neurological status.
• 12 hourly electrolyte and coagulation studies
43. ALF: common complication
Encephalopathy
cerebral edema
Raised ICP
Infection
Coagulapathy
Hypoglycemia
Dyselectrolytemia
Acid base disturbance.
Multi-organ failure
45. Encephalopathy
Treatment
Low protein by month.
Lactulose 10-50ml 2-4 hourly
Acid enema: Lactulose enema, vinegar-can be given
6 hourly
Treat sepsis, bleeds and electrolyte imbalance.
Avoid sedation
Flumazenil : Short lived results.
46. Cerebral Edema
Treatment
• Nurse the child 20-30° elevated ¯ ICP
• IV mannitol
• Hypertonic saline
• Hyperventilation may help ¯ ICP
• Hypothermia ¯ ICP
• Avoid hyperthermia.
47. Bleeding
Treatment
Inj. Vitamin K
Fresh frozen plasma (FFP).
Platelet transfusion -If platelet<10000/mm3 or
platelet count<50000 with bleeding.
Fresh whole blood transfusion.
Recombinant factor VII.
48. Acid Base Changes
Treatment
• Volume expansion.
• Dopamine infusion.
• NaHCO3.
• Mechanical ventilation for R.acidosis.
• Plan for liver transplantation.
49. Septicaemia
:
Gram-positive (in 2/3rd cases):
Staphylococcus
Streptococci
Gram-negative (in 1/3rd cases):
Fungal infection
50. Septicemia
• Septic workup : culture blood, sputum & urine
• Cefuroxime, Amoxycillin, Fluconazole.
• Fungal infection : IV amphoterecin .
• We use fluconazole orally.
• Iv cefuroxime and flucloxacillin
51. Renal complication
Renal failure may occur in 50% pt. with ALF
Due to
Hepatorenal syndrome.
ATN by due to sepsis, endotoxemia, bleeding
hypotension.
Directly by nephrotoxic drug.
56. Extracorporeal Liver Assisted Device(ELAD)
Artificial
Bioartificial
To bridge liver transplantation or
regeneration of native liver
To remove toxic substances to
improve survival and HE
58. King’s College Criteria For liver transplantation.
Acetaminophen cases
Arterial PH < 7.3 or
Arterial lactate>3.5 at 4
hrs or
Arterial lactate>3 at 12
hrs
INR>6.5 &
Cr>3.4 &
Stage 3 or 4
encephalopathy
Non-acetaminophen
cases
INR>6.5 or
Any 3 of the followings:
Age<10 or >40 yrs
Duration of jaundice>7
d
Total Bili>17.5
INR>3.5
Etiology: idiosyncratic
drug, halothane,
idiopathic, non-A non-
B hepatitis
59. Liver Transplantation
Survival increased from 20% to 60-80% in various
studies
Has changed the outlook & the natural course
61. Overall mortality with supportive care exceeds
70 percent.
With intensive medical support survival rate 50-
60 % in acetaminophen overdose and fulminant
HAV or HBV infections.
In idiopathic form of ALF or acute onset of
Wilson disease mortality rate is 80-90% .
62. Prognosis
The prothrombin time is the best indicator of
survival.
73% of children with an< INR 4 surviving versus only
4 of 24 (16.6%) with an> INR 4.
This is now the widely accepted criteria.
Bhaduri BR, Mieli-Vergani G. Fulminant hepatic failure:pediatric aspects.
Semin Liver Dis 1996;16:349-355.
63. Poor prognosis is seen in :
age less than 1 year
stage 4 encephalopathy
INR more than 4
Need of dialysis before transplantation