2. Learning Objective
• Understand the different types of Acute hepatic
failure (AHF)
• Acute Liver Failure (ALF)
• Acute-on-Chronic Liver Failure (AoCLF)
• Post-hepatectomy liver failure
• Appropriate therapies and support of the liver
• Role of transplantation and other advanced support
3. ALF definition
Development of severe hepatic dysfunction
within 6 months of the onset of symptoms
in the absence of chronic liver disease
• Acute Hepatitis with elevation AST/ALT
• INR>1.5
• Encephalopathy
Hyperacute, Acute or Subacute
6. AoCLF
Acute hepatic insult manifesting as jaundice
and coagulopathy, complicated within
4 weeks by ascites +/- encephalopathy in a
patient with previously chronic liver disease
Bil >85 μmol/L and INR >1.5 mandatory
AoCLF vs end stage CLF
9. Post hepatectomy liver failure
Impaired ability of the liver to maintain its synthetic,
excretory and detoxifying functions characterised by
impaired coagulation and hyperbilirubinaemia on or
after postoperative day 5.
50/50 definition - PT >50% and Bilirubin >50μmol/L
Grade A, B and C
17. Paracetamol OD
• Common poisoning
• <1% cases of OD result in significant
hepatotoxicty
• CYP450 convert paracetamol to NAPQI
• NAPQI EXTREMELY hepatotoxic
• Usually conjugated with hepatic glutathione
18. Paracetamol OD
• Bad
• Malnutrition, ETOH abuse, enzyme inducing drugs
• Large staggered OD
• Delayed presentation and initiation of NAC
• N-acetylcysteine augments glutathione levels
• NAC highly effective if delivered within 8-12hrs
• Prescott normogram used to determine risk
19. Cardiovascular
• Hyperdynamic and hypervolaemic
• Moderate incidence adrenal dysfunction
• CO monitoring and fluid responsiveness
• PAC
• Right ventricular cardiomyopathy
• Hepatopulmonary shunt and pulm Ht
• Noradrenaline
21. Coagulopathy
• Coagulation
• Low fibrinogen
• Low levels of II, V, VII, IX, X, APC, Protein C/S
• Mixed fibrinolytic/antifibrinolytic effects
• ‘Auto-anticoagulation’ vs prothrombotic
• NO routine correction of INR (incl for lines)
• Thromboelastometry helpful (TEG vs ROTEM)
• Everything changes if bleeding
• Generally platelets/fib 1st
• FFP/cyro vs PCC/FCC
• TXA and Calcium
22. Ventilation
• Hepatopulmonary syndrome and shunting
• Pulmonary hypertension may need ↓PVR
• IAH/IACS
• Early intubation for Grade III/IV HE
• Neuroprotection vs standard ARDsnet
• LRTI/VAP common, low threshold for Abx
• Consider paracentesis in IACS
23. Encephalopathy and cerebral
oedema
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Common in ALF and grade III/IV HE and NH4 >150
Cytotoxic and vasogenic/hyperaemic in origin
Poor autoregulation
ICP>25mmHg and CPP<50mmHg bad prognosis
Sepsis/SIRS detrimental
Reverse Jugular venous oximetry
ICP bolt risk vs benefit
TBI like ICP management
NO evidence for neuromonitoring
CRRT/plasma exchange
24. Hepatorenal Syndrome
• Not the commonest cause of AKI in AHF
• ATN/nephrotoxic drugs/glomerulonephritis/IACS
• HRS diagnosis of exclusion
• Type 1 vs Type 2
• Results from reduced perfusion
• Splanchnic vasodilation
• Poor autoregulation
• ↓ renal prostaglandin synthesis and other vasoactive mediators
• HAS/terlipressin
• Early CRRT
25. Renal Replacement Therapy
• Haemofiltration vs HD/HDF?
• Some low level evidence for NH4+ clearance
• Start early
• Esp if Grade III/IV HE and NH4+>150
• Aim for dose of 35ml/kg/hr (Calculated vs actual
dose received?)
• No evidence for high volume haemofiltration
26. Microbiology
• Highly susceptible to infection
(LRTI/SBP/urinary/lines/wounds)
• SIRS/hyperdynamic/endotoxin translocation vs Bacteraemia
• Proven rates of 80% bacterial and 30% fungal
• Gram +ve in 1st 3-4 days followed by gram –ve and fungal
infections
• Prophylaxis offers no mortality benefit
• Maintain high vigilance
• Refer to local guidelines and micro team
27. ALF transplant Criteria
• Paracemol vs non paracetamol
• King’s college criteria
• Paracetamol
• pH <7.3 >24hrs post overdose
• Grade III/IV HE + Creat >300 + PT >100s
• Non Paracetamol
• pH <7.3 or PT >100s
• HE III/IV with any 3 of the following
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Age <10 or >40
Bil >300
Jaundice to HE time <7 days
PT >50s
Seronegative hepatitis or drug induced
28. Transplant
• Multidisciplinary decision
• Specialised service managed at supraregional centres
• If in doubt=refer/discuss
• Outcomes from transplant depend on ALF vs AoCLF vs CLF
• Live donor vs DBD vs DCD. Orthotopic and Domino Tx
• Complex anaesthetic+++
• Protocolised ICU post op management
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TEM guided coagulation (balance bleeding vs HA/anastomosis flow)
Antibiotics
Immunomodulation
Early US and dopplers
MDT approach
29. Artificial Liver Support
• Bridge to transplant or recovery?
• Evidence?
• Detoxifying systems
• Albumin dialysis
• MARS (albumin dialysis/detoxifying and de-ionising columns)
• Plasmaphoresis with FFP promising in ALF
• Bioartificial Systems
• Extracorporeal liver perfusion old technology
• Other systems using hepatocytes
• ELAD study pending publication
31. Conclusion
• Don’t forget the basics
• Resuscitate the patient
• Good ICU house keeping
• ALF vs AoCLF vs CLF
• Antidotes/Specific Rx where appropriate
• Complex/systemic disease with multi-organ
effects
• EARLY referral/discussion with a liver unit
