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.
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.
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”
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.
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
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.
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
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
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
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
Grade 1,ii rare
Grade iii 25-35%
Grade iv 65-75%
Cerebral oedema most common cause of death.
In america ALFSG index used which includes patient gcs,bilrubin,inr,sr phosphorus,and sr M30 (ELISA based marker of apoptosis)..Limited use as M30 not available everywhere.Better prognostic indicator than KCC.
Improved mortality due to orthoptic liver transplant and better critical care.
Research difficult due to rare and heterogenous nature with rapidly progressive course but result from application of other research e.g from cerebral edema management has improved mortality.
Reduces IL 17 levels in Non paracetamol ALF pts.
In pcm overdose replinishes glutathione stores and detoxifies NAPQ1 highly reactive,toxic metabolite of paracetamol overdose.
Most common cause of death-cerebral oedema.
20_25% deaths in ALF due to intracranial hypertention and BS herniation.
HE four compatible theories
Cerebral vasomotor dysfunction
Oedema secondary to ammonia toxicity
Inflammation due to SIRS
putative benzodiazepine-like molecules
Complication rate with ICP monitor 3.8%,fatal haemorrhage 1%
Common organisms growing klebsiella oxy, VRE, Enterococcus faecium.
Prophylactic antibiotics for greatest risk pts as mentioned above.