1. Acute liver failure MBBSPPT.COM

2. DEFINITION
Acute liver failure (ALF) is not a diagnosis but a clinical syndrome
evidence of liver dysfunction within 8 weeks of onset of symptoms/liver disease
uncorrectable coagulopathy with INR >1.5 in patients with hepatic encephalopathy or INR> 2.0 in patients without encephalopathy
No evidence of chronic liver disease either at presentation or in the past.

3. Adult Vs pediatric liver failure
Etiology: infective & metabolic cause
Clinical picture : encephalopathy is difficulty to diagnose
Etiology : drugs predominant cause
Clinical picture : encephalopathy essential criteria

4. Grades of hepatic encephalopathy

5. Etiology of ALF in India
Acute viral hepatitis ( most common-60-95%) hepatitis A 10-54%;hepatitis E 3-27%; hepatitis B 8-17%; and multiple viruses 11-30%- commonest being hepatitis A+E. Acute liver failure secondary to hepatitis B usually presents at about 12 weeks of age. Drugs (6-8%) Indeterminate (13-20%)

7. Etiology of acute liver failure
Neonate/infant up to 6 months
Infection: septicaemia, hepatitis B, adenovirus, echovirus,Coxsackie B.
Metabolic: neonatal haemochromatosis, tyrosinaemia typeI, mitochondrial disorders, fatty acid oxidation defects.
Poisoning: paracetamol.
Familial haemophagocytic syndrome.

8. Etiology Children >6 months
Viral hepatitis: hepatitis A/B/E/non-A-G, Epstein-Barrvirus, parvovirus B19.
Autoimmune type I or II.
Drug induced: paracetamol overdose, sodium valproate,carbamazepine, isoniazid,halothane.
Metabolic: Wilson’s disease( most common >3yr), Reys syndrome

9. Clinical Presentation
Clinical presentation depends on the etiology of FHF.
Usually acute.
Can be prolonged to 10 weeks if due to metabolic liver disease.
The extent of jaundice is variable in the early stages, but all children have coagulopathy.

10. Clinical Presentation
Encephalopathy is particularly difficult to diagnose in neonates.
Vomiting and poor feeding are early signs
Irritability and reversal of day/night sleep patterns indicates more established hepatic encephalopathy.
Older children: aggressive behavior or seizures.

11. Clinical Presentation
Hypoglycemia is present in 40% of patients with ALF.
Due to increased plasma insulin levels secondary to reduced hepatic uptake, and reduced glycogen stores gluconeogenesis.

12. SYMPTOMS Fever Vomiting /poor feeding Easy brusibility Jaundice
Altered sensorium, irritability, inattention, altered sleep rhythm
Developmental delay
Seizure

13. SIGNS Trouble drawing figures Poorly performed mental tasks
Asterexix in older children
Incontinence
Fetor hepaticus
Hyperreflexia ( stage II &III)
Areflexia , decortications &decerebration/faccidity, extensor plantar (stage IV)

14. DIAGNOSTIC WORK-UP General work-up
ALT, AST, GTT,ALK total and conjugated bilirubin, PT(INR), PTTK, hemogram, serum electrolytes, blood urea, creatinine, blood and urine cultures, blood group, chest X-ray, serum AFP, lactate, LDH, blood ammonia,ABG, and urine for reducing substances

15. Specific work-up
Infectious IgM anti- hep A, IgM anti - hep E, HbsAg, IgM anti- hepatitis B core antibody, cytomegalovirus PCR, IgM VZV, IgM EBV, HIV 1 and 2 Wilson disease Serum ceruloplasmin, 24 hour urinary copper estimation, KF ring. Clue to etiology: alkaline phosphatase / bilirubin ratio <4.0,AST/ ALT ratio > 2.2 ± evidence of Coombs negative hemolysis

16. Specific work-up Autoimmune
Coombs test, antinuclear antibody (> 1:40), liver kidney microsomal antibody, smooth muscle antibody (>1:20), Immunoglobulin G levels
Drug overdose
Acetaminophen, valproate drug levels

17. Management of ALF Key Components:
Prevent complications such as encephalopathy and cerebral edema, sepsis, gastrointestinal bleeding, renal failure, electrolyte imbalance and multiorgan failure.
To assess prognosis and consider liver transplantation.

18. MANAGEMENT Transport ( HE I &II )
Management in the Intensive Care Unit
Fluid balance: 75% maintenance.
Volume resuscitation if necessary
Vasopressor for saline unresponsive shock
Glucose based solution ( minimum GIR 4-6 mg/kg/mt) should be used
Sedation should be avoided

19. How frequently clinical &biochemical parameters should be monitored
vital signs every 4 hours
continuous oxygen saturation monitoring
neurological observations/coma grading, electrolyte , ABG, blood sugar every 12 hourly ; PT should be monitored 12 hourly
daily measurements of liver span
liver function tests, blood urea, serum creatinine, calcium and phosphate at least twice weekly.
Surveillance of blood and urine cultures

20. Management of Electrolyte disturbances
Hyponatremia, hypokalemia, hypocalcemia, hypophosphatemia and hypomagnesemia and hypoglycemia are commonly observed
Intravenous fluids should be tailored in accordance to electrolyte, sugar and renal status of the patient.

21. Supportive management
NAC therapy for all ALF
prophylactic administration of PPI
L-ornithine L-aspartate, lactulose and other non-absorbable antibiotics have not been found to be beneficial
lactulose is administered in grades I-II HE

23. Management of raised ICT
Infection and cerebral edema remain the leading causes of death.
Routine invasive ICP monitoring is not recommended
Hypertonic saline Vs mannitol
Routine hyperventilation is not recommended
Hypothermia, routine phenobarbitone and steroids are not indicated

24. Management of coagulopathy
Prophylactic use of FFP and platelet transfusion is not recommended
Clinical significant bleeding is indication of FFP transfusion
Vit k 5-10mg single dose is indicated in all patients of ALF
INR > 7 is another indication
Platelet transfusion is given at a threshold value of or bleeding with platelet count < /cumm

25. SEPSIS IN ALF
Staph , strepto and gram-ve organism are the predominat organism
Candida is responsible for 30% cases
Routine preventive antibiotics not recommended
Indications of emperical antibiotics
surveillance cultures reveal significant isolates, progression of, or advanced stage (III/IV) HE, refractory hypotension, renal failure, presence of SIRS components (temperature >38°C or <36°C, white blood count >12,000or <4,000/mm3, tachycardia)

26. Acute kidney injury in ALF
Causes
Pre renal ( hypovolumia, hepato renal syndrome )
Renal ( ATN )
Indications of Renal replacement therapy
persistent hyperkalemia (>7 mEq/L),
uremic encephalopathy,
fluid overload (pulmonary edema,severe hypertension), severe metabolic acidosis,
Hyponatremia (120 mEq/L or symptomatic) or
Hypernatremia.

27. Nutrition Use of BCAA in ALF and HE is controversial
Protein restriction is not recommended in HE
High calorie diet
If metabolic cause is suspected then stop nutrition for 24 h

28. Liver transplantation
Indications
INR> 4
Factor V < 25%
Contraindications
uncontrollable and untreatable sepsis,
Severe cardiopulmonary disease, multi-organ failure,
Extrahepatic malignancy, mitochondrial disease,
HE grade IV encephalopathy

29. Prognosis Mortality is 70% without LT Poor prognostic factors
elevated serum bilirubin and prothrombin time, young age
high arterial ammonia and high WBC count,
low alanine aminotransferase, and presence of encephalopathy
drug-induced ALF (non- acetaminophen), hepatitis B, and indeterminate cases (25% spontaneous survival).

30. Prognosis The prognosis is better with hepatitis A,
acetaminophen overdose
ischemia (approximately 60% spontaneous survival)

31. Thank You