pptx & Case Discussion

1. PALF
(Pediatric Acute Liver Failure)
13/7/2023
Dr Farha Khan
MBBS, MD (Pediatrics)
PICU Consultant, Max Super speciality Hospital, Patparganj, Delhi, India
PICU Fellowship- Royal Brompton & Harefield (NHS London, UK)
ECMO (CICU) Fellowship- Great Ormond Street Hospital (NHS London, UK)
PCICU Fellowship – Apollo Hospital (Delhi, India)

2. Definition
• Acute liver dysfunction with heterogenous underlying etiologies and rapid progression
resulting in significant morbidity and mortality
Latest guidelines for the diagnosis and management - released by
North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition
(NASPGHAN) and
European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN)
[1]

3. PALF Study Group consensus entry criteria
• Due to difficult precise assessment of hepatic encephalopathy in infants and
children, current guidelines suggests – PALF Study Group consensus entry criteria
• To identify cases of severe acute liver injury that could cause deterioration
resulting in death or liver transplant
• the criteria do not include paediatric chronic liver diseases that present as ALF

4. PALFSG Entry Criteria for Child With Acute Liver Failure
(All three components required)
Acute onset liver disease with no evidence of chronic liver disease
Biochemical evidence of severe liver injury
Coagulopathy not corrected by vitamin K:
• PT ≥15 or INR ≥1.5 with encephalopathy or
• PT ≥20 or INR ≥2 with or without encephalopathy

5. Clinical presentation & History
• H/o exposure to infectious agents (like recent travel or any contact) or
toxins (like chemicals, medications, illicit drugs or wild mushrooms)
• H/o Consanguity, autoimmune diseases, liver disease, multiple late
miscarriages, early infant death or developmental delay - suggestive of
underlying autoimmune or metabolic cause

6. Examination
Early identification features of hepatic encephalopathy -
• altered sleep wake cycle, confusion, disorientation
• increased tone, brisk reflexes, positive Babinski sign
Clinical features suggestive of CLD –
hepatosplenomegaly, ascites, pedal edema, stunting, signs of vitamin D
deficiency, spider angiomas

7. Hepatic
Encephalopathy
grading
West Haven

9. • In developed countries, acetaminophen toxicity accounting for 13.3% with
idiopathic etiology in 30-50%
• Application of standardized diagnostic test helped reduce the percentage of
Indeterminate PALF from 48% to 30.8% [5].
• In India, viral infections followed by metabolic liver diseases and drug
induced liver injury with only 9-14.6% cases being of indeterminate etiology
[3,4].
• Liver biopsy in indeterminate PALF (IND-PALF) - help in identification of a
recently defined sub-set, with dense CD103+ CD8+ T-cell hepatic infiltrates,
benefitting from immunosuppressive therapy [6].

10. Management
• Timely treatment prevent complications & improve
survival
• Recommended fluid therapy with 90% of maintenance to
prevent over-hydration precipitating cerebral, pulmonary
& peripheral edema;
• Underhydration can cause hepatorenal syndrome [8],
hypotension and worsening of encephalopathy
• PALF with cardiovascular dysfunction, noradrenaline is the
vasopressor of choice f/by low dose vasopressin can be
added [10]
• Evidence based beneficial effect of lactulose in prevention
and management of hepatic encephalopathy [9]
• Limited data on role of invasive (ICP) monitoring in PALF &
is case specific
• Goals of ICP monitoring added to facilitate the decision

13. The 2022 guidelines are envisioned to improve patient survival
and prompt further studies for better non-invasive diagnostic
techniques, neuromonitoring and new therapeutic modalities.

14. Case Presentation

15. Clinical
Presentation
6years /female/ 19kg
C/O
• Pain abdomen for 7 days
• Fever for 2 days
• Vomiting for 2 days
• Decreased oral intake for 1 day
• Reduced urine output for 12 hours

16. Details of symptoms
• Pain abdomen – dull, generalized, no radiation, no aggravating & relieving
factors
• Fever- mild to moderate, undocumented, no association with chills & rigors,
intermittent, relieved with meds
• Vomiting- non projectile, non bilious, contains food particles, small in amount
• No H/o of any drug overdose, no h/o mushroom intake, no known allergies

17. Examination
• GC unsatisfactory
• Afebrile/ Pallor+, jaundice+/CRT<3sec
• Chest –b/l air entry equal
• CVS-S1 S2normal, no murmur, good volume pulses
• CNS-alert oriented, no altered sensorium/ GCS 15, no signs
of hepatic encephalopathy
• P/A-Soft, distended, BS + liver 2-3cm BCM, Spleen NP,
flanks mild fullness, passing stool (no bleeding/melena)
AG=57cm
• Over the course of hospital stay- liver regressed and ascites
developed with persistent uncorrectable INR
HR 100/MIN
RR 24/MIN
MAP 65 mmHg
SPO2 99% AT RA
TEMP 97.5 F

18. USG Abdomen –on admission
• Liver normal size, shape, echogenicity
• CBD normal, Portal vein normal
• No obvious Pancreatic pathology noted
• Spleen normal
• No free fluid in abdomen/pelvis
• No features suggestive of portal hypertension or chronic liver disease

19. Lab Parameters
27/6/23 29/6/23 30/6/23 01/07/23 02/07/23 03/07/23
HB 8.3 5.3 8.9
TLC 9.4 10.5 13.9
Platelets 280 197 229
N 74 57 65.6
CRP 14.1
INR 2.38 2.56 2.87 2.53 2.8 2.61
PT 27 29.2 32.7 28.8 31.9 29.7
aPTT 40.8 38.9
Blood Group : O Positive

20. Electrolytes
27/6/23 28/6/23
Na 130 133
K 2.66 3.25
Ca 106.9
urea 16.6
Cr 0.52
Cl 106 114

21. Viral markers
27/6/23
HAV-IGM 0.01
HBsAg Neg (0.22)
HCV -IGG Neg (0.19)
HEV - IGM 0.89

22. Liver Function Tests
27/6/23 29/6/23 30/6/23 01/07/23 02/07/23 03/07/23
Total protein 6.39 6.34 5.75 6.56 7.25
Albumin 2.47 2.35 2.04 2.26 2.41
Total Bil 8.05 11.22 7 4.5 3.77
Direct bil 3.32 4.56 3.17 2.06 1.59
Indirect bil 4.73 6.66 3.83 2.44 2.18
SGOT/ AST 681 489 340 265 219
SGPT/ALT 314 110 55 38 50 64
GGTP 213 183 131 129 130
A:G Ratio 0.63 0.59 0.55 0.53 0.5
ALP 34 19 30 41
INR 2.38 2.56 2.87 2.53 2.8 2.61

23. 29/6/23 01/07/23 02/07/23
s. Ceruloplasmin <5.5 mg/dl
s. Ammonia 112
24 hr Urinary copper 1538.75
ANA NEG (1:100)
Retic Count 7
PCV 21.3

24. PS for Hemolysis -02/07/23
• RBC – Anisopoikilocytosis (++), Macrocytosis(++), few crenated RBC,
polychromatophils, occasional schistocyte seen
• WBC—Counts within normal limits. Neutrophilia present
• Platelets- adequate
• DCT negative evidence of hemolysis present

25. Referrals
• Atypical low liver enzymes for acute hepatitis and
persistent low albumin levels raise the possibility of
underlying liver pathology needing further evaluation
Pediatric Gastro -
• Autoimmune Panel
• Wilson’s work-up
• Ophthalmology referral
EYE Examination –
• No KF rings seen
• In view of persistent uncorrectable INR despite daily
vitamin K correction and high bilirubin, indicating
referral to a liver transplant center

26. Differential
diagnosis &
testing
(Based on age &
suspected etiology)
Suspected etiology &
Recommended test

27. Thank you

28. Management
rapid age-based pertinent diagnostic evaluation,
prompt initiation of specific and supportive therapy irrespective of the
underlying etiology
monitoring for early identification in the ICU setting &
management of complications
Early transfer to liver transplant centre, wherever indicated

29. REFERENCES
1. Squires JE, Alonso EM, Ibrahim SH, et al. North American Society for Pediatric
Gastroenterology, Hepatology, and Nutrition Position Paper on the Diagnosis and Management
of Pediatric Acute Liver Failure. J Pediatr Gastroenterol Nutr. 2022;74:138-58.
2. Lutfi R, Abulebda K, Nitu ME, et al. Intensive care management of pediatric acute liver
failure. J Pediatr Gastroenterol Nutr. 2017;64: 660-70.
3. Alam S, Khanna R, Sood V, et al. Profile and outcome of first 109 cases of paediatric acute
liver failure at a specialized paediatric liver unit in India. Liver Int. 2017;37:1508-14.
4. Kaur S, Kumar P, Kumar V, et al. Etiology and prognostic factors of acute liver failure in
children. Indian pediatr. 2013;50:677-9.
5. Narkewicz MR, Horslen S, Hardison RM, et al. A learning collaborative approach increases
specificity of diagnosis of acute liver failure in pediatric patients. Clin Gastroenterol Hepatol.
2018; 16:1801-10.
6. Chapin CA, Burn T, Meijome T, et al. Indeterminate pediatric acute liver failure is uniquely
characterized by a CD103+ CD8+ T cell infiltrate. Hepatology. 2018;68:1087-100.
7. Chapin CA, Mohammad S, Bass LM, et al. Liver biopsy can be safely performed in pediatric
acute liver failure to aid in diagnosis and management. J Pediatr Gastroenterol Nutr.
2018;67:441-5.
8. Lui PMF, de Carvalho ST, Fradico PF, et al. Hepatorenal syndrome in children: A review.
Pediatr Nephrol. 2021;36:2203-15.
9. Gludd LJ, Vilstrup H, Morgan MY. Nonabsorbable disaccharides for hepatic encephalopathy:
a systematic review and meta-analysis. Hepatology. 2016;64:908-22.
10. Wendon J, Panel M, Cordoba J, et al. EASL Clinical Practical guidelines on management of
acute (fulminant) liver failure. J Hepatol. 2017;66:1047-81.

30. Suggesting
Reconsideration
of the criteria for
initiation of
optimal
interventions