Dr Aftab Ahmad Siddiqui JNMC AMU Aligarh

1. Fulminant Hepatic Faliure
• BY Dr Mohd. Moaaz Kidwai
• Moderator- Dr. Sunil Mehendiratta

2. Overview
• In 1970, ALF was classically defined as FHF in
patients with no prior liver disease in which
rapidly deteriorating hepatocellular function
ensued within 8 weeks
• It was redefined by O'Gradey et al. in 1993, who
used the term ALF to describe a clinical syndrome
in which encephalopathy occurs between 8 and
28 days after the onset of jaundice
Further subclassification depending on the
jaundice-to-encephalopathy time-
• hyperacute -onset within 1 week
• acute – between 8 days and 4 weeks
• subacute -between 29 days and 12 weeks

3. defintion
The currently accepted definition in children
includes-
• biochemical evidence of acute liver injury (usually
<8 wk duration)
• no evidence of chronic liver disease
• and hepatic-based coagulopathy defined as (PT)
>15 sec or INR >1.5 not corrected by vitamin K in
the presence of clinical hepatic encephalopathy
or
• PT >20 sec or INR >2 regardless of the presence
of clinical hepatic encephalopathy.

4. Etiology
• ALF is rare and represents a syndrome, rather
than a specific disease.
• the results of a recent multicenter study of
ALF identified acetaminophen overdose as the
most frequent cause in the United States (46%
of cases) (3) as well as in European countries
(7).
• On the other hand, in Africa and Asia, viral
hepatitis remains the leading cause of ALF

6. Pathophysiology
• The mechanisms that lead to FHF are poorly
understood
• Massive destruction represent both a direct
cytotoxic effect and hyperimmune response
Whatever the initial cause of hepatocyte injury,
various factors can contribute to the pathogenesis of
liver failure, including -
• Impaired hepatocyte regeneration,
• Altered parenchymal perfusion
• Endotoxemia
• Decreased hepatic reticuloendothelial function

8. Clinical features
• Presentation is mostly like septic shock
• Progressive jaundice, fetor hepaticus, fever,
anorexia, vomiting, and abdominal pain are
common
• These symptoms finally lead to the
development of encephalopathy
• Eventulally MODS and death due to herniation

11. Management
• Initial Assessment
• Investigations and monitoring
• Immediate management
• Specific treatment
• Treatment of complications
• Liver transplantation

12. Initial Assesment
• History- onset, mentl status, bleeding
- Drug, GDD, seizures
- F/H
Examination-Assesment of growth and nutrition
- Signs of CLD
- CNS exam, Liver span.

13. Investigations
• CBC, SE, RBS, ABG
• LFT, RFT, PTINR
• Blood Amonia, Lactate
• Viral markers , Autoimmune markers
• USG abdomen
• Screen for wilson disease
• In neonates and infants-

14. Monitoring
• Vitals
• 12 hrly CNS exam and coma grading
• 12hrly SE, ABG, RBS
• Daily coagulation studies and CBC
• Daily liverspan and weight
• LFT, Urea, S.Cr, Ca and phos. twice weekly
• Input and output chating
• Blood and urine cultures
• Daily prescription review

15. Immidiate management
• Need for mech. Vent. if grade 3-4 enceph.
• Avoid sedatives
• Central venous line-
• Volume resuscitation and vasoactive drugs
• Once euloumic – gvie 3/4th IVF with GIR=6-
8mg/kg/min
• Prophylactic use of PPI
• Care of comatose

16. Specific treatment
HBV Lamivudine
HSV Acycloir
Acetaminophen NAC
Autoimmune hepatitis Methyl prednisolone 60mg/kg iv
Galactosemia Galcatose and lactose free diet
HFI Fructose free diet
Tyrosinemia Nitisone, Diet low in tyrosine and
phenyalanine
Neonatal hemochromatosis Antioxidant cocktail

17. Treatment of complications
• Metabolic
• Encephloathy
• Cerebral edema
• Coagulopathy
• Renal failure
• Infections
• Dietary support

18. Metabolic Abnormality
• Hyponatremia- dilutional
• Hypokalemia- reduced intake and urine losses
- add KCL to IVF
• Hypophoshatemia- liver regeneration
Early phosphorus administration is associated
with better prognosis.
• Hypoglycemia-frequent monitoring needed
• Acid Base status- metabolic acidosis and
respiratory alkalosis

19. Encephalopathy
• Close CNS monitoring frequently
• Identify and correct precipitating factors
• Restrict protein intake
• Bowe wash with several enemas.
• Lactulose every 2-4 hr orally or by NGT in
doses (10-50 mL) sufficient to cause diarrhea
• Oral or rectal administration of rifaximin or
neomycin.(nonabsorbable A/B)

20. Cerebral edema
• 70-80% of stage 3-4 Encephalopathy pts.
• Most common cause of death
Mgmt-
• Mechanical vent. with low PEEP
• Monitor the ICP
• Head end elevation
• Can use mannitol or 3% NS

21. Coagulopathy
• Due to decreased synthesis of clotting factors,
increase in peripheral consumption and at least
some degree of DIC and TCP.
• prophylactic treatment with FFP in the absence
of bleeding is unadvised.
• FFP infusion and platelet transfusion are advised
before invasive procedures and also in presence
of clinically significant bleeding.
• Plasmapheresis and Factor VIIa.

22. Renal Failure
• Causes- Hypovoloumia, sepsis, HRS
Hepatorenal Syndrome
• Due to renal vasoconstriction
• Two types based on rate of progression
• Type 1- rapidly prog. with doubling of S.Cr in
less than 2 weeks
• Type 2- gradually prog. type
• TIPS procedure or vasoconstrictor drugs
• Continuous hemodiaysis

23. Infections
• Monitor closely for infection- sepsis,
pneumonia, peritonitis, and UTI.
• Mostly gram +ve but –ve and fungal also.
• Serial blood cultures for bacteria and fungi.
• Both antibacterial and antifungal is
recommended for patients with significant
isolates on surveillance cultures, refractory
hypotension, or clinical evidence of SIRS.

24. Dietary support
Component Recommended intake
Energy 150% of recommended allowance
Carbohydrate 15-20g/kg/day
Fat 8g/kg/day and 50% as MCT
Protein in non encephalopathic state 2-3g/kg/d
Protein in encephalopathic state Grade 1-2=1-2g/kg/d
Grade 3-4=0.5-1g/kg/day

25. Temporary Liver support
• bridge for the patient with liver failure to liver
transplantation or regeneration.
• Nonbiologic systems-albumin containing
dialysate (MARS, SPAD, Promethius)
• Biologic liver support devices - liver cell lines
or porcine hepatocytes.
• Infusions of hepatic stem cells

26. Liver Transplantation
TYPES-
• Orthotopic liver transplantation
• Reduced-size allografts and living donor
transplantation- in infants
Indication- when hepatic decompensation is
imminent or has occurred

27. New Therapies Undergoing Current
Trial
• To date, the NAC trial is one of the very few
controlled trials in ALF and its results remain
controversial
• A blinded, controlled trial performed in India
using L-ornithine L-acetate infusions in 203
patients with ALF- no benefit
• Ornithine phenyl acetate, is currently under
consideration

28. Prognosis
• Varies with the cause of liver failure and stage
of hepatic encephalopathy.
• Brainstem herniation is the most common
cause of death
• Various prognostication scores developed

29. Poor prognosis markers
• Liver necrosis and multiorgan failure
• Age <1 yr, stage 4, an INR >4, and the need for
dialysis before transplantation
• Ammonia >200 μmol/L is associated with a 5-
fold increased risk of death
• Sepsis, severe hemorrhage, renal failure,
apastic anemia

31. Take Home Message
• ALF often is missed and the clinical scenario
resembles septic shock.
• Drug intake should be considered when the
history is obscure or pt is in coma
• Determining etiology of ALF is essential to
management and understanding prognosis
• Do not replace clotting factors unless bleeding is
actually occurring—use INR as a prognostic tool.
• Ammonia-lowering agents may prolong short-
term survival.
• Listing for transplantation should be done timely

32. THANK YOU