This document summarizes the case of a 56-year-old male with acute liver failure who underwent liver transplantation 8 years ago. He presents with jaundice, confusion, and feeling unwell. On examination he has hypotension, tachycardia, and signs of vasodilatory shock. Blood tests show deranged liver function and metabolic acidosis. The document defines acute liver failure and outlines its etiology, prognosis, pathophysiology, investigations, treatment of complications including cerebral edema and infection, and the role of liver transplantation.

1. Acute Liver failure
Wahid Altaf

2. Case…Thursday evening call from AnE
registrar
 Mr C.E. 56 Year old male.
 Presenting complaint of
Jaundice
Confusion
Feeling unwell
 Background history, liver transplant 8yrs ago with
normal liver functions untill 20 days back.

3. Further questioning
 Hypotension
 Tachycardia
 Vasodilatory shock
 Severe Compensated Metabolic acidosis Ph 7.37 HCO3 14
lactate 8
 Blood Glucose 2.5
 Deranged Liver functions.( Bilirubin 116, ALP 357,
GGT 103,AST 1241,ALT 873).

4. Definition of Liver failure
“The abrupt loss of hepatocellular function in a patient
with previously normal liver function, the expression of
which includes coagulopathy and encephalopathy.”
AASLD…“Evidence of a coagulation abnormality
(INR>1.5) and mental alteration (encephalopathy) in a
patient without pre-existing cirrhosis and with an illness
of <26wks duration”

5. Encephalopathy

6. Classification

7. Parradox
 Rapid onset ALF ----> higher risk of cerebral
edema but better prognosis for recovery
 Classic example: Paracetamol OD
 Slow onset ALF -----> lower risk of cerebral
edema, higher risk of portal hypertensive
problems (e.g. ascites, variceal bleeding),
and ultimately poorer prognosis (w/o
transplant)
 Classic example: NANB hepatitis

8. Etiology

9. Common drugs causing ALF
 Isoniazid
 Sulfur Antibiotics
 Nitrofurantoin
 Azole antifungals
 Antiepileptics- Phenytoin, sodium valproate.
 Herbals-ex kava kava,ma huang,comfrey.
 Ibuprofen
 Statins

10. Prognosis…family

11. Poor prognosis
 Phone a friend, call
Your consultant
Don’t hesitate to call
St. Vincent University Hospital.

12. Mortality
 Hospital survival
Mid 1970”s ….. 17%
Mid 2000”s …... 62%

13. Pathophysiology
 Death of a mass of hepatocytes.
 Loss of vital synthetic and metabolic hepatic functions.
 Sterile inflammatory condition leading to SIRS.
 Aim of management is to halt progression from hepatic
impairment to MODS.

14. Investigations
 ALT, AST, ALP,GGT.
 Bilirubin, Ammonia, Lactate.
 Blood glucose, Coags: PT, aPTT, INR, Albumin.
 Electrolytes, Mg, Phos.
 Arterial blood gas
 FBC with differential.
 Drug screening, paracetamol levels

15. Investigations.
 If under 35 years of age
Ceruloplasmin, Serum & urine copper
 Anti HAV IgM
 Anti HBc IgM/ Anti HBsAg
 Anti-HCV
 Pregnancy test
 Autoimmune markers – ANA, ASMA, Ig levels
 HIV status
 Amylase & lipase

16. Invstg
 Diagnostic imaging
 Liver biopsy

17. Imaging
 Microbiology : Strep parasanguinus and candida.

18. Ammonia levels
 >75 mcg/l …Encephalopathy
 >200 mcg/l…Cerebral oedema and raised ICP.

20. Cause-Specific therapy

21. Cause-specific therapy

22. N-Acetylcysetine
•May improve circulatory function and oxygen delivery
•No improvement in overall survival but significant improvement in
transplant-free survival with encephalopathy grade 1-2.
Time to NAC administration important
Time in hrs Mortality (%)
<12 0.4
>12 6
>24 13
>48 19
•Now generally recommended for all patients with ALF

23. When to pick up the phone in
paracetamol overdose
 D2-
 pH <7.3
 INR>3
 Cr >200
 Hypoglycaemia
 D3-
 HE
 Cr>200
 INR >4.5
 D4-
 Any rise in INR
 Cr >250
 HE

24. Good ICU housekeeping
 Stress ulcer prophylaxis
 No DVT prophylaxis
 Feeding
 Blood glucose management
 Electrolytes like phosphate and magnesium.

25. Lines
 Ultrasound guided
 No correction of coagulopathy
 Arterial line
 Central line
 Vascath

26. Severe Vasodilatory shock
 Optimise cardiac filling pressures
–Haemodynamics can be challenging to determine given
the disruptive effects of liver failure on the vasculature
 Saline challenge, albumin.
 Vasopressors

27. Vasopressors
 Nor-Adrenaline
 Terlipressin
 Vasopressin..no evidence of splanchnic ischemia.

28. Sedation
 Avoid if possible
 Propofol/Remifentanyl is reasonable

29. Pulmonary considerations
 Airway
–Elective intubation
–Elective intubation once in grade 3 encephalopathy
 Rapid intubation technique
–Avoid spikes in ICP or decreased CPP
 Pneumonia
–Commonest site of sepsis
 Acute lung injury/ARDS
–In one third of patients

30. Renal failure
 Renal failure in 50%
 Particularly common with paracetamol overdose
–Liver and renal metabolites

31. Management
 Volume control
 Maintenance of blood pressure
 Prevention/treatment of sepsis
 Judicious selection of drugs
 Early use of renal replacement therapy
–Before fluid problems aggravate cardiovascular status and
ICP
–Sodium management
–Better ammonia level management

32. Complications of acute liver failure
and management

33. Management of complications
 Cerebral edema
 Sepsis
 Coagulopathy

34. Cerebral oedema

35. Predictors of cerebral edema
•Rapid onset ALF
―Rapid accumulation of glutamine overwhelms astrocytes'
ability to exclude organic osmolytes
•Grade 3-4 encephalopathy
―High ammonia concentrations
•Infection and/or SIRS
―Case for prophylactic antibiotics
•Vasopressor therapy
•Renal replacement therapy

36. Invasive monitoring of ICP

37. Delaying the onset of raised ICP

38. Delaying the onset of raised ICP

39. Delaying the onset of raised ICP

40. Two principles in management of
cerebral oedema

41. Raised ICP management
 1st line Mannitol
 2nd line Hyperventillation to PaCO2 25-35mmhg
 3rd line Hypertonic saline, Hypothermia
 4th line Barbiturates, Anticonvulsants
 Other considerations Transplantation, total
hepatectomy.

42. Infection
•Infection is near-universal
–Failing liver results in failed host defences
–Infection precipitates MOSF, cerebral oedema
–Frequent cause of death
•Organisms
–Bacterial and fungal
–Gram negative organisms (52%) more frequent than
Gram-positive organisms (44%) and Candida Infection

43. Sites of sepsis

44. Recommendations
 Minimize invasive procedures, strict asepsis
 Daily chest radiograph and surveillance cultures
 Empiric broad spectrum antibiotics for those patients
at greatest risk:
–Grade 3-4 encephalopathy
–Renal failure
–Any component of SIRS
–Planned transplantation (includes antifungals)

45. Coagulopathy
 Increased INR present by definition
 Thrombocytopenia present in up to 70%
 TEG is reassuring

46. Is there bleeding diathesis?
 Significant bleeding is uncommon: 5%
–Anticoagulant proteins decrease in parallel with coagulation
factors
–Spontaneous intracranial haemorrhage is rare
 Less clinically-significant bleeding may occur from several
sites
–Gastric mucosa
–PPIs
 Invasive procedures offer the greatest risk

47. Correcting coagulopathy before
invasive procedures
 Correction itself carries risks
–Volume overload
–Aggravation of ICP
–Transfusion-related acute lung injury
–Thromboembolism (particularly with recombinant Factor
VIIa)
 Commonly used goal of INR <1.5 untested, lacks scientific
basis
 Correction obscures underlying trends in INR which are
important prognostically.

48. Correcting coagulopathy before
invasive procedures
 FFP not encouraged except to correct coagulopathy before invasive procedure
–Effect modest, short-lived
–Does not improve survival
 Platelet transfusions
–Rarely necessary
 Recombinant activated Factor VII
–Is effective
–Cost
–Short-lived effect
–Prothrombotic

49. Other options
 Liver transplant
 MARS.. Extracorporeal support, dialysis against albumin.
 CRRT against albumin.

50. Liver transplant
Accepted Indications Absolute contraindications
Acute Liver Failure Brainstem herniation
Decompensated cirrhosis with
MELD>15
Severe intracranial hypertention
(ICH>50)
Hepatocellular criteria with Milan
criteria
Advanced cardiopulmonary
disease.Haemodynamic
unstability,requiring high dose
pressors
Hilar cholangiocarcinoma Uncontrolled infection
Hepatopulmonary syndrome Multiorgan failure
Portopulmonary hypertention Current/Recent extrahepatic
malignancy unless tumour
free>2yrs
Primary hyperoxaluria Untrated alcoholism/Drug use
Cystic fibrosis with liver
involvement
Severe uncontrolled mood
disorders

51. Palliate
 Declined by liver services
 Refractory ICP
 Blown pupils
 Communication skills
 Don’t forget morphine infusion.

52. In summary
•Causes
•Help
•Bloods
•NAC
•Early lines, don’t be afraid
•Drugs, dialysis
•Raised ICP
•Coagulation
•Manage Infections
•Transplant
•Palliate