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
5.
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
7.
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
9.
10.
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
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
30.
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
This sub-classification reflects not only the cause of the disease and probable complications, but also the differences in the survival rate for these groups, with the hyperacute group paradoxically having the best prognosis
. It is unknown why only approximately 1-2% of patients
with viral hepatitis experience liver failure.
Sedatives should be avoided unless
needed in the intubated patient because these agents can aggravate or
precipitate encephalopathy. Opiates may be better tolerated than benzodiazepines
Gastrointestinal hemorrhage, infection, constipation, sedatives,
electrolyte imbalance, and hypovolemia can precipitate encephalopathy
and should be identified and corrected
trapping of ammonia in acidic intestinal contents.
Monitoring intracranial
pressure can be useful in preventing severe cerebral edema, in maintaining
cerebral perfusion pressure, and in establishing the suitability
of a patient for liver transplantation
the decrease in prothrombin
time after FFP administration decreases the accuracy
with which prognosis can be judged and second, FFP
administration results in a volume load that might
deteriorate renal function and increase ICP
Terlipressin nor epi and mododrine
Molecular adsorbent recircultion system. Pingle pass albumin dialysis
