36 slides to summarise the topic especially for postgraduate trainees

1. Pediatric Acute Liver Failure
(PALF)
Dr. Aniruddha Ghosh
Institute Of Child Health, Kolkata

2.  Definition & etiologies
 Diagnostic modalities : general & special - based on
etiologies
 Which parameters are to be monitored ?
 Complication-targeted treatment approach: latest
recommendations
 Few words regarding Liver Transplantation
Objectives

4. Acute Liver Failure :
Definition
(a) Evidence of liver dysfunction within 8 weeks of onset of symptoms
(neonates may have only deranged liver functions without overt symptoms)
(b) Uncorrectable coagulopathy(6-8 hours after administration of one dose of
parenteral vitamin K) with
INR > 1.5 in patients with hepatic encephalopathy
Or
INR > 2.0 in patients without encephalopathy
(c) No evidence of chronic liver disease either at presentation or in the past
1) Hyper acute < 8 days
2) Acute 8 – 28 days of jaundice before HE
3) Sub acute > 28 days

5. Etiologies of ALF in India
Viral
drug induced
others
Viral
hepatitis
61-95%
Drugs 6-8%
Other
causes
9-10.5%
Viral ALF
Hep A
Hep B
Hep E
Multiple virus
Hep A 10-54 %
Hep B 8-17 %
Hep E 3-27%
Multiple virus
(MC A+E) 11-30%
Unestablished etiology : 6-22 %

6. INFECTIVE
• Hepatitis virus A,B,C,D,E,?G
• Herpes Simplex
• Adenovirus, Epstein-Barr
virus, parvovirus,
cytomegalovirus, echovirus,
varicella,
dengue, coxsackie
• Fungal or bacterial sepsis
DRUG REACTIONS and
TOXINS
• Dose-dependent:
Acetaminophen, halothane
• Idiosyncratic reaction:
Isoniazid, NSAIDS, phenytoin,
sodium valproate,
antiretrovirals
• Drug combinations: Isoniazid-
rifampicin, trimethoprim
sulfamethoxazole,
Co amoxiclav
• Toxins: Mushroom poisoning,
herbal products

7. METABOLIC:
• Wilson’s disease, galactosemia, tyrosinemia
• hereditary fructose intolerance
• Niemann-Pick disease type C, mitochondrial cytopathies
• congenital disorder of glycosylation.

8. What investigations to order ?
In general and specific

9. ALT, AST, GGT, Alk.phos, total/conj. Bil, P time (INR), APTT
CBC, Electrolytes, Urea, Creatinine, Blood & Urine cultures,
Blood group, CXR,
serum Alpha Fetoprotein, Lactate, LDH, Ammonia,ABG, Urine
for reducing substances
IgM anti-Hep A, IgM anti-Hep E, HBsAg, IgM HBcAg,
CMV PCR, IgM VZV, IgM EBV, HIV 1 and 2
Serum Ceruloplasmin, 24 hr urinary copper, eye check up for
KF ring
Coomb’s test, ANA (> 1:40), Liver Kidney Microsomal
antibody, Smooth muscle antibody (> 1:20), Immunoglobulin
G levels
Serum triglycerides, Cholesterol, Ferritin, Bone Marrow
Biopsy
Acetaminophen, Valproate drug levels
Toxicology screening
General
work- up
Infections
Wilson disease
Autoimmune
HLH
Drug
overdose &
Toxins

10. Principal concerns for Management
Acute Liver Failure
Encephalopathy
Coagulopathy
Electrolyte
imbalance
Sepsis
Acute
Kidney
Injury

11. What to monitor ? How to monitor?
Vital signs including BP 4 hrly*
SpO2 continuous
Coma grading
Electrolytes, ABG, CBG
12 hrly*
P time 12 hrly till pt stabilises or
decision to perform
transplant is taken
Liver span
Prescription review
24 hrly
LFT
Urea,Creatinine
Ca, Phosphate
At least twice weekly
Surveillance of blood &
urine cultures
On regular basis until final
reports come
* = more frequently in unstable child

12.  Maintenance fluids-10% dextrose in 0.9% NS
 Total Na intake 0.5-1 mmol /kg/day
 Total K+ intake 3-6 mmol /kg/day
 Monitor for : Hypocalcemia /hypomagnesemia /hypophosphatemia
 Maintain urine output using
Frusemide 1-3 mg/kg every 6hr
Dopamine 5mcg/kg/min
Colloid/FFP
Fluid & Electrolytes

13.  Blood glucose <40mg/dl
 Can cause CNS dysfunction
 Causes:
↓ hepatic gluconeogenesis
↑insulin
↑glucose utilization
Secondary bacterial infection
 i.v. 10-50% dextrose bolus
 GIR 4-6mg/kg/min to start with and titrate
Hypoglycemia

14. Coagulopathy
 Causative factors : Platelet dysfunction, Hypofibrinogenimia, Vitamin K
deficiency
 Routine correction not recommended.
 Prophylactic FFP is not recommended – doesn’t reduce risk of significant
bleeding and obscures the trend of INR as a prognostic marker
 FFP : Where to give?
- significant bleed
- Invasive procedure i.e. Central venous line
- extreme coagulopathy with INR > 7
Dose: 15-20 ml/kg every 6 hr
or
3-5 ml/kg/hr continuous
infusion

15.  Vitamin K1 : single dose (5-10 mg, slowly with rate not more than
1mg/min) is recommended empirically in all ALF pts.
 Cryoprecipitate : Where to give ?
- Significant hypofibrinogenemia (< 100 mg/dl)
 Recombinant factor VIIa : costly but effective option, when....
- Prolonged INR despite giving FFP
With volume overload
 Platelet transfusion : When ?
- 10,000-20,000/cmm threshold reached OR
- significant bleeding with < 50,000/cmm
 Safe platelet level during invasive procedure in ALF:
50,000-70,000/cmm

16. Sepsis
 Major cause of mortality in ALF
 ORGANISMS : MC organisms : Gm positive cocci(Staphylococci, Streptococci)
enteric gram-negative bacilli
Fungal particularly Candida albicans
 Prophylactic parenteral/enteral antibiotic does not improve outcome / survival.
 Empirical antibiotic therapy : Indications:- surveillance cultures reveal isolates
- Progression of, or advanced HE (III/IV)
- Refractory hypotension
- Renal failure
- SIRS components
- Pts listed for liver transplantation
 broad spectrum coverage (3rd gen. Cephalosporin + vanco/teicoplanin +
fluconazole) recommended for empirical therapy

17. Raised ICP & Hepatic encephalopathy
IV a : arousable with painful stimuli
IV b : no response to pain
 ICP monitoring (invasive method) not routinely recommended
 Serial doppler / CT/ MRI used for monitoring

18. Pathogenesis

19. Bedside EEG : Useful diagnostic tool for
assesment of encephalopathy

20. Mannitol : Gradually losing it’s place...
 Indications : obvious signs of herniation, ICP 25 mmHg< for over 10 mins
 Dose : IV bolus over 15 mins 0.25-1 g /kg, 20 % mannitol
 Can be repeated if serum osmolality <320 mosmol/L
 Urine output monitoring
 Ultrafiltration in setting of renal impairment

21. • No role of restriction of dietary protein
• Lactulose 1-2ml/kg every 4-6hrly orally/ by NG tube to produce
2-3 loose motions daily
• Enteral antibiotics- rifaximine
• Treat precipitating factors- sepsis, dehydration, electrolyte
imbalance, hemorrhage, hypoglycemia
• Avoid sedation, short acting barbiturate(midazolam) if required
• Flumazenil- short lived improvement
• Anticovulsants (if seizures present)-phenytoin / phenobarbitone
• Management of cerebral edema

22. Acute Kidney Injury
• Pre renal (hypovlemia, hepatorenal syndrome) or Intrinsic
renal (ATN)
• Blood Urea unreliable – synthesis impaired in hepatic
dysfunction
• FeNa helps to differentiate
Rx :
• Intravascular volume expansion
• Modify doses of nephrotoxic drugs : simple but often
overlooked point

23. What about dialysis ?
• Indications for Renal Replacement Therapy (RRT)
1) Severe/ persistent Hyperkalemia (>7 mEq/L)
2) Uremic encephalopathy
3) Intractable volume overload (pulm. Edema, severe
HTN)
4) Severe metabolic acidosis
5) Hyponatremia (120 mEq/L or symptomatic)/
Hypernatremia
• Peritoneal dialysis preferred in sick, unstable, infants
• Hemodialysis avoided in pts who are
hemodynamically unstable/ have bleeding tendency/ very young

24. N-acetyl cysteine : myth or truth ?
Does it really work in ALF other
than paracetamol overdose?

25. “In conclusion, NAC is safe in non-
acetaminophen-induced ALF. In this
retrospective study NAC was
associated with a shorter length of
hospital stay, higher incidence of native
liver recovery without
transplantation, and better survival
after transplantation.”
Liver Transpl 14:25-30, 2008. © 2007
AASLD.
[Duration of use : 1-77 days,
median : 5 days]

26.  Acetaminophen poisoning : For a total of 21 hours of infusion. Some
patients may require more than 21 hours of N-acetylcysteine.
 Liver failure due to other causes: same dose as above. Continue 6.25
mg/kg/hr infusion until resolution of encephalopathy, decreasing
aminotransferases and improvement in coagulopathy.
150 mg/kg over 1 hr 5% D or ½ DNS
12.5 mg/kg/hr X 4 hrs 5% D
6.25 mg/kg/hr X 16 hrs 5% D
Dose
&
Diluent

27. Mushroom & Drug induced toxicity :
What does AASLD say?

28. Hepatic Replacement
Therapies

29. • LT is the only definite
treatment
• King’s College Hospital
(KCH) criteria, pediatric
end-stage liver disease
(PELD) score, APACHE II,
and Clichy criteria
• INR >4 or factor V
concentration of <25% as
the best available criteria
for listing for LT
Liver Transplantation
32%
22%11%
9%
9%
4%
13%

31. Molecular Adsorbent
Recirculating System
Cell-Free Non-Biological Artificial Support system

32. Extracorporeal Bioartificial
Liver Support Devices
• HepatAssist 2000
• ELAD : Extracorporeal Liver Assist Device
• BLSS : Bioartificial Liver Support System
• MELS : Modular Extracorporeal Liver System
• LiverX2000 system
• AMC-BAL (Academic Medical Centre), Chamuleau
(combine hepatocytes in a plastic cartridge and semi-
permeable membrane)

33. • The mortality rate may reach 80-90% in the absence of liver
transplantation.
• Patients with stage 3 or 4 encephalopathy have a poor prognosis.
• A short time from jaundice to encephalopathy is associated
paradoxically with improved survival.
• ALF due to acetaminophen toxicity generally has a relatively
favorable outcome.
• Brainstem herniation is the most common cause of death
Prognosis

34. • Encephalopathy is difficult to recognise in children
• Unless acute hemorrhage is present / an invasive
procedure is performed, empiric transfusion with fresh
frozen plasma (FFP) is not warranted
• Despite technical difficulties and a donor organ shortage,
the results of liver transplantation is promising .Therefore,
early referral to a specialized center for liver
transplantation is vital.
To summarise...

35. References

36. Thank You for Your
Patience