Fulminant hepatic failure is a clinical syndrome resulting from massive liver cell necrosis or impairment. It is characterized by coagulopathy and encephalopathy that develops over less than 8 weeks. The liver loses its synthetic, excretory, and detoxifying functions. Causes include viral hepatitis, drugs like acetaminophen, and metabolic disorders. Presentation includes jaundice, fever, vomiting, and confusion. Treatment focuses on supportive care, treating complications, and sometimes liver transplantation. Prognosis depends on factors like age, etiology, and development of complications.

2.  Fulminant hepatic failure is a clinical syndrome of
coagulopathy and encephalopathy resulting from
massive necrosis of hepatocytes or from severe
functional impairment of hepatocytes.
 The disease evolves over a period of 8wks from the
onset of precipitating illness.
 Synthetic, excretory, and detoxifying functions of the
liver are all severely impaired.

3.  The current criteria suggested by pediatric acute liver
failure study group ( PALFSG)
 Biochemical evidence of acute liver injury (<8 wk
duration)
 No evidence of chronic liver disease
 Hepatic-based coagulopathy defined as a prothrombin
time (PT) >15 sec or international normalized ratio
(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.  Previously asymptomatic children with chronic liver
disease like wilsons disesase, galactosemia and
other metabolic conditions can also present with
fulminant hepatic failure for the first time.

5.  ETIOLOGY:
 IDIOPATHIC: in 40-50% cases
 INFECTIVE
 VIRAL CAUSES
• Hepatitis a,b,c,d & e
• high risk of fulminant hepatic failure occurs in combined
infections with the hepatitis B virus (HBV) and hepatitis D.
• EBV
• Adenovirus
• Enterovirus
• Cmv
• Parvovirus B19
• Herpes simplex
• Varicella zoster

6.  BACTERIAL
• Enteric fever
• Weil’s disease
• Septicemia
 PROTOZOAL
• Facliparum malaria

7.  DRUGS:
• Acetaminophen overdose is the most common
etiology of acute hepatic failure in children and
adolescents
• Isoniazid
• Sodium valproate
• Phenytoin
• Salicylates
• Halothane
• Exposure to carbon tetrachloride, Amanita
phalloides mushroom, herbal medication,methanol.

8.  METABOLIC CAUSES:
• Wilsons disease
• Hemochromatosis
• Galactosemia
• Alpha 1 anti-trypsin deficiency
• Hereditary tyrosinemia
• Hereditary fructose intolerance
• Neonatal iron storage disease
• Defects in β-oxidation of fatty acids
• Deficiencies of mitochondrial electron transport

9.  CIRCULATORY CAUSES
• Budd-chiari syndrome
• Myocarditis
• Acute circulatory failure
• Cyanotic heart disease
 IMMUNOLOGICAL CAUSES
• Auto immune hepatitis
 MISCELLANEOUS
• Reye’s syndrome
• Acute leukemia ( infiltration)
• Graft vs host disease
• Hyperthemia

10.  CLINICAL PRESENTATION:
 Some children with fulminant hepatic failure may present
with or without features of encephalopathy
and some present only with coagulopathy in the
absence of sepsis or DIC.
SYMPTOMS:
• Jaundice
• A prodrome of flu-like illness may precede the onset of
jaundice
• Fever
• Anorexia
• vomiting

11. • Abdominal pain
• Foetor hepaticus
• Confusion
• Restlessness
• Neuropsychiatric changes
• Irritability
• poor feeding and disturbance in sleep pattern in infants
• Bleeding manifestations- hematemisis, hematochezia,
melena.
• Altered sensorium
• coma

12.  EVALUATION OF CHILD
• H/O fever
• H/O onset of jaundice
• Constitutional symptoms like vomitings
• H/O bleeding
• H/O decreased urine output
• H/O altered sensorium
• H/O i.v drug abuse

13. • H/O herbal medication
• Similar illness in family or community
• H/O mushroom eating
 Past history of ATT, anticonvulsant therapy
 Developemental history :
• Failure to thrive
• Developemental delay
• Neuromuscular weakness

14.  Family history of consanguinity , early infant death, liver
disease.
 Per abdominal examination: liver size, tenderness,
ascites
 CNS examination: level of consciousness, other causes
of altered sensorium

15.  INVESTIGATIONS
 Investigations for ascertaining liver cell injury
• Serum bilirubin-both direct and indirect are increased
• Hepatic enzymes do not correlate with the severity of
fulminant hepatic failure. ALT and AST are normal or
increased or even decreased. The enzymes are
decreased if the liver cell necrosis is severe.
• Liver biopsy – autoimmune hepatitis, metastatic liver
disease, lymphomas.

16.  Investigations for aetiological factors
• CBP- WBC increased in infections
• Viral markers-hepatitis B (HBV-DNA, antibody to HBV,
HBsAg, IgM core antigen), hepatitis A (IgM anti-HAV),
hepatitis C (anti-HCV, HCV-RNA) and hepatitis D (anti-
HDV antibody)
• Blood culture and sensitivity

17. • Serum paracetamol levels, other drug levels in
poisonings
• Autoantibodies-LKM, ANA and SMA
• Urine/serum screening test for metabolic disorders
• Blood ammonia is elevated in Reye's syndrome
• Seum ceruloplasmin levels
• Blood urea levels decreased in urea cycle disorders

18.  Investigations for complications:
• ABG- metabolic acidosis and respiratory alkalosis
• blood sugar levels
• Serum lactate levels
• RFT: Blood urea and Serum creatinine levels
• Serum electrolytes- hyponautremia , hyperkalemia.
• Prothrambin time elevated it doesnot respond to vit k
administration.
• Imaging: ultrasound abdomen, CT/MRI brain for
cerebral edema and to ruleout other causes of altered
sensorium.

19.  Management:
 supportive
• Children with fulminant hepatic failure should be
admitted in icu with continuous monitoring of vital
functions. Minimal handling of the child.
• Maintain a normal fluid balance. Avoid fluid overload.
• Correction hypoglycaemia.
• Maintain normal urine output.

20. • Administration of calcium, phosphorus, magnesium,
factor concentrate, magnesium and platelets.
• Coagulopathy can be treated with parenteral vitamin K,
fresh frozen plasma, cryoprecipitate.
• Prophylactic use of broad spectrum antobiotics,
antifungals

21. • Maintain a platelet count of more than 50,000.
• Gut sterilisation-using antibiotics such as
ampicillin/neomycin.
• Lactulose inhibits colonic organisms, decrease the
intestinal transit time.
• Fat soluble vitamin supplementation.
• Diet with decreased protein, high calories, high
carbohydrates and moderate fat should be given.

22. • Prophylactic use of proton pump inhibitors because of
the high risk of gastrointestinal bleeding.
• In complicated cases endotracheal intubation may be
required to prevent aspiration, to reduce cerebral
edema by hyperventilation, and to facilitate pulmonary
toilet.
• Mechanical ventilation and supplemental oxygen are
often necessary in advanced coma.

23. • Sedatives should be avoided unless needed in the
intubated patient because these agents can aggravate
or precipitate encephalopathy.
• Patients should be monitored closely for sepsis,
pneumonia, peritonitis, and urinary tract infections.
• Gastrointestinal hemorrhage, infection, constipation,
sedatives, electrolyte imbalance, and hypovolemia can
precipitate encephalopathy and should be identified and
corrected.

24. • liver dialysis with an albumin-containing dialysate, and
biologic liver support devices that involve perfusion of
the patient’s blood through a cartridge containing liver
cell lines or porcine hepatocytes can remove some
toxins, improve serum biochemical abnormalities.
• Orthotopic/auxillary orthotopic liver transplantation can
be lifesaving in patients who reach advanced stages of
hepatic coma.

25.  Specific
• Paracetamol poisoning-N-acetylcysteine
• Hepatitis B -antiviral agents lamivudine,entecavir
• Herpes simplex- acyclovir
• Galactosaemia, fructosaemia, hereditary tyrosinaemia
type I-dietary elimination.
• Autoimmune hepatitis-steroids, azathioprine

26. • BZD antagonist like flumazenil in BZD over dosage
• Enteric encephalopathy- ceftriaxone
• Wilson’s disease- D-pencillamine,zinc
• Hemochromatosis- desferoxamine, deferiprone
• Leptospirosis- pencillins, doxycycline
• Malaria- anti malarials
• Amanita posoning- pencillins
• L-ornithine and L-aspartate preparation (LOLA)
removes ammonia by conversion to urea through the
urea cycle.

27.  COMPLICATIONS:
• Infections
• Hepatic encephalopathy
• Cerebral edema
• Hepatorenal syndrome
• Hepatopulmonary syndrome
• Coagulopathy –GI bleeding
• Hypotension
• Electrolyte and acid base imbalance

28.  POOR PROGNOSTIC FACTORS:
• Age < 1 yr
• Depending on etiological factor
• Stage 4 encephalopathy
• INR > 4
• Plasma ammonia concentration > 200 micro mol/ L
• Sepsis
• Severe bleeding

29.  HEPATIC ENCEPHALOPATHY
• Hepatic encephalopathy is a complex neuropsychiatric
syndrome characterised by disturbances in level of
consciouness, behaviour and personality seen in
patients with acute or chronic liver disease.
• Type A- seen in fulminant hepatic failure
• Type B- seen in portosystemic shunt cases
• Type C- seen in chronic liver disease

30.  PATHOGENESIS:
• Accumulation of neurotoxins in brain
• Increased activity of the inhibitory GABA
neurotransmission system
• Imbalance between aromatic and branched amino acids
• Action of cytokines and bacterial lipopolysaccharide on
astrocytes

32.  DIFFERENTIAL DIAGNOSIS
• Organic brain diseases
• Intracranial lesiom-intracranial bleeding
• Infections-meningitis, encephalitis
• Metabolic encephalopathy-hypoglycaemia, electrolyte
imbalances, hypercarbia, an<Xlia, uraemia
• Toxic encephalopathy
• Postseizure encephalopathy
• Hyperammonaemia
• Alcohol intoxication

33.  MANAGEMENT
• Same as above but may require ventilatory support.