1. Management of Acute Liver
Failure
Dr Ganapathi S Kini
DNB Trainee

2. Management
• General
• CNS complication
• Infection
• Metabolic
• Coagulopathy
• Hemodynamic
• Renal failure
• Prognosis predictor

3. General Considerations
• Though etiologically different , ALF have a common
clinical features:
a) Acute loss of hepatocellular function.
b) Systemic inflammatory response.
c) Multi-organ failure.

4. Circulatory dysfunction
• Agents tried in circulatory dysfunction in ALF include
– Prostaglandin
– N Acetyl Cysteine
Sterling RK, Luketic VA, Sanyal AJ, Shiffman ML. Treatment of fulminant hepatic failure with intravenous
prostaglandin E1. Liver Transpl Surg 1998;4:424-431 .

5. • Sterling RK, Luketic VA, Sanyal AJ, Shiffman
ML. Treatment of fulminant hepatic failure
with intravenous prostaglandin E1. Liver
Transpl Surg 1998;4:424-431

6. • Lee WM, Hynan LS, Rossaro L, Fontana RJ, Stravitz
RT, Larson AM, et al. Intravenous N-acetylcysteine
improves transplant-free survival in early stage non-
acetaminophen acute liver failure. Gastroenterology
2009;137:856-864.

8. Mechanism of N Acetyl Cysteine in
non paracetamol ALF
• May improve systemic circulation parameters.
• Improve liver blood flow.
• Improve liver function in patients with septic
shock.
Rank N, Michel C, Haertel C, Lenhart A, Welte M, Meier-Hellmann A, et al. N-acetylcysteine increases liver
blood flow and improves liver function in septic shock patients: Results of a prospective, randomized,
double-blind study. Crit Care Med 2000;28:3799-3807.

9. CNS Complication
• Cerebral edema
• ICH
• Uncal herniation

10. Causes of CNS Complication
• Osmsotic disturbance in brain.
• Loss of autoregulation leading to increase blood
flow.
• Increased S ammonia level.
• ? Inflammation & infection.

11. • Cerebral edema seldom in Grade I/II HE
• In 25 – 35% Grade III HE.
• In 65 – 75% or > Grade IV HE .
Daas M, Plevak DJ, Wijdicks EF, Rakela J, Wiesner RH, Piepgras DG, et al. Acute liver failure: results of a 5-year clinical
protocol. Liver Transp Surg 1995;1:210-219.

12. Management of grade I/II HE.
• Consider transfer to liver transplant facility & listing for
transplantation.
• Brain CT: r/o other causes.
• Avoid stimulation
• Avoid sedation.
• Lactulose ?possibly helpful.

13. Management of grade III/IV HE
• Intubate trachea (may require sedation)
• Elevate head of bed.
• Consider placement of ICP monitoring device.
• Immediate treatment of seizures required prophylaxis
of unclear value.

14. • Ellis AJ, Wendon JA, Williams R. Subclinical seizure
activity and prophylactic phenytoin infusion in acute
liver failure: a controlled clinical trial. Hepatology
2000;32:536-541.

16. • Bhatia V, Batra Y, Acharya SK. Prophylactic
phenytoin does not improve cerebral edema
or survival in acute liver failure — a controlled
clinical trial. J Hepatol 2004;41:89-96.

17. Management of grade III/IV HE
• Mannitol severe elevation of ICP or first clinical signs
of herniation.
• Hypertonic saline to raise serum sodium to 145-155
mmol/L.
• Hyperventilation effects short-lived & may use for
impending herniation.
Murphy N, Auzinger G, Bernal W, Wendon J. The effect of hypertonic sodium chloride on intracranial
pressure in patients with acute liver failure. Hepatology 2002;39:464-470.

18. • Murphy N, Auzinger G, Bernal W, Wendon J.
The effect of hypertonic sodium chloride on
intracranial pressure in patients with acute
liver failure. Hepatology 2002;39:464-470

19. • N 30 (ALF with Grade III/IV HE
HS – 15 Vs Placebo – 15.
• Increase vassopressor
HS – 0% Vs Placebo – 86.66% (P <0.001)
• Decrease in ICP
HS – 86.66% Vs Placebo – 0% (P=.003)
• ICP significantly higher in control group (P=.04)

20. • Uncontrolled experimental studies have
shown benefit of Short-acting barbiturates or
hypothermia for intracranial hypertension
refractory to osmotic agents as a bridge to
liver transplantation.
Forbes A, Alexander GJ, O’Grady JG, Keays R, Gullan R, Dawling S, et al. Thiopental infusion in the treatment of
intracranial hypertension complicating fulminant hepatic failure. Hepatology 1989;10:306-310.
Jalan R, Damink SWMO, Deutz NEP, Lee A, Hayes PC. Moderate hypothermia for uncontrolled intracranial
hypertension in acute liver failure. Lancet 1999;354:1164-1168.

21. Infection
• Periodic surveillance for infection.
• Prompt antimicrobial treatment.
• Antibiotic prophylaxis not shown survival
benefit.
Rolando N, Wade J, Davalos M, Wendon J, Philpott-Howard J,Williams R. The systemic inflammatory
response syndrome in acute liver failure. Hepatology 2000;32:734-739.

22. Coagulopathy
• Vitamin K.
• FFP for invasive procedures /active bleeding.
• Platelets transfusion for invasive procedures /active
bleeding.
• Recombinant factor aVII possibly effective for invasive
procedures
• Prophylaxis for stress ulceration: give H2 blocker/PPI

23. Hemodynamics
• Volume replacement.
• Pressor support in hypotension refractory.
• Mean arterial pressure >75mm of Hg.
Stravitz RT, Kramer DJ. Management of acute liver failure. Nat Rev Gastroenterol Hepatol 2009;6:542-
553.

24. Renal Failure
• Functional or ATN
• Avoid nephrotoxic drugs (NSAIDs)
• Continuous mode of RRT is preferred.
• Contributes to mortality.
Davenport A, Will EJ, Davidson AM. Improved cardiovascular stability during continuous modes of renal
replacement therapy in critically ill patients with acute hepatic and renal failure. Crit Care Med 1993;
21:328-338.

25. Metabolic Concerns
• Glucose.
• Supplementation of K+, Mg+2 & phosphate.
• Enteral or total parenteral nutrition.

26. Prognosis predictors.
• US multi-centre study of ALF, etiology of ALF was
predictors of outcome i.e.,
a) Transplant free survival >=50% in ALF due to
Acetaminophen
Hepatitis A
Shock Liver
Pregnancy related disease

27. • b) Transplant free survival < 25% in ALF due to
1) Idiosyncratic drug injury
2) Acute hepatitis B (& other non-hepatitis A viral
infections)
3) Autoimmune hepatitis
4) Mushroom poisoning
5) Wilson disease
6)Budd-Chiari syndrome
7) Indeterminate cause

28. Other predictors
• Renal dysfunction in non-paracetamol ALF.
• Degree of hepatic encephalopathy.

29. King’s College Criteria
• Acetaminophen-Induced ALF.
• Non-Acetaminophen-Induced ALF.

30. Acetaminophen-Induced ALF
1. Strongly consider OLT listing if:
a) arterial lactate >3.5 mmol/L after early fluid resuscitation
2. List for OLT if:
a) pH <7.3 - or -
b) arterial lactate >3.0 mmol/L after adequate fluid
resuscitation
3. List for OLT if all 3 occur within a 24-hour period:
a) presence of grade 3 or 4 hepatic encephalopathy
b) INR >6.5
c) Creatinine >3.4 mg/dL

31. Non-Acetaminophen-Induced ALF
• List for OLT if:
INR >6.5 and encephalopathy present (irrespective of grade)
OR
• Any 3 of the following (encephalopathy present; irrespective of
grade):
a) Age <10 or >40
b) Jaundice for >7 days before development of encephalopathy
c) INR 3.5
d) S. Bilirubin >17mg/dl.
d) Unfavorable etiology, such as
Wilson Disease
idiosyncratic drug reaction
seronegative hepatitis

32. THANK YOU