2. Metabolic
◦ Carb metabolism
◦ Protein and lipoprotein metabolism
◦ Fatty acid metabolism
◦ Biotransformation of drugs
Storage
◦ Glycogen
◦ Vitamins A, D, E, and K
◦ Iron and copper
3. Immunological function s
◦ Synthesis of immunoglobulins
◦ Phagocytosis by Kupffer cells
◦ Filtration of bacteria
◦ Degradation of endotoxins
Excretion of bilirubin and urea formation
Haematological functions
◦ Blood reservoir
◦ Haematopoiesis in the foetus
4. • Syndrome that leads to MOF and death
o Previously normal liver may fail within days
• High grade encephalopathy, survival is
<20%
• Early death:
o cerebral oedema, CVS collapse
• Late death:
o Sepsis , MOF
5. • ALF: Sd. defined by
o Encephalopathy
o Coagulopathy
o Jaundice
o Individual with previously normal liver
6. • Fulminant Hepatic Failure
o Potentially reversible condition
o Consequence of severe liver injury
o Encephalopathy appears within 8 wks. of
initial Sx.
o Absence of pre-existing liver ds.
7. • King’s classification:
o Hyperacute: encephalopathy within <7 days
Paracetamol, ischaemic, viral, toxins
o Acute: 8-28 days
o Subacute: 5-26 weeks
Seronegative, idiopathic, drug-related
Different etiology
Poorer prognosis
8. Cause Agent Responsible
Viral Hepatitis Hep. A, B, D, E, CMV, HSV, seronegative
hepatitis (14-25% in UK)
Drug-related Dose-related, e.g.paracetamol; idiosyncratic
reactions, e.g. anti-TB, statins, recreational drugs,
anticonvulsants, NSAIDs, many others
Toxins Carbon tetrachloride, amanita phalloides
Vascular events Iscahemic hepatitis, veno-occlusive disease,
Budd-Chiari, heatstroke
Other Pregnancy-related liver disease, Wilson’s disease,
lymphoma, carcinoma, trauma
9. • Most common causes:
o Worldwide:
Hepatotrophic viruses A-E
o UK
Paracetamol overdose
Seronegative or non-A-E hepatitis
Idiosynchratic drug rxs. or Wilson’s ds.
10. • Identify the etiology
o Hx., examination, viral and autoimmune
profiles
• Bloods
o FBC, EUC, CMP, coags, LFTs, drug levels
• Abdo USG and CT
o Vascular pattern, ascitis, splenomegaly
11. • Liver Bx.
o Done by transjugular route
o Mays suggest specific Dx.
o Watch for sample from healthy liver
o >50% necrosis assoc. with poor prognosis
o Need to reverse coagulopathy before doing
it
12. • Depend on the severity, which depends
on:
o Etiology
o Speed of onset of symptoms
• Non-specific
o N&V, abdo pain
• Neurological
o Confusion, agitation, coma
13. • Mortality is higher for Grade III/IV
o Mostly due to cerebral oedema
o Occurs in 80% of pts. w/ALF
Due to lack of equilibration of osmotic gradient
30% of those have cerebellar tonsil and/or
temporal lobe herniation causing death
o We’re now better at treating cerebral
oedema
14. • Elevated ICP
o HTN, bradycardia, blown pupils: occur late
o CTB won’t tell you
o ICP monitor is best way of knowing
• CVS changes
o Similar to sepsis
o Might be due to infection
15. • Renal failure
o Oliguric
o Poor prognosis
Except with paracetamol overdose where it has
a good prognosis
• Impaired immunity
o Decreased complement synthesis, Kupffer
cell dysfunction, poor neutrophil adhesion
and superoxide production
16. • Increased susceptibility to infection
o 80% of pts. have bacteriologically proven
infections
o Major sepsis is contributor to death in 20%
of cases
Staph. aureus 70% of gram (+)
E. Coli most common gram (-)
C. albicans in 30% of pts.
17. • Pts. need HDU/ICU
• Need CVC and continuous IBP
monitoring and IDC
• Baseline ABG and lactate
o Lactate >3mmo/L after adequate resus has
same sensi. and speci. for death as The
King’s College Hospital criteria
18. • Early indicators of prognosis in fulminant
hepatic failure.
O'Grady JG, Alexander GJ, Hayllar KM, Williams R.
Gastroenterology. 1989 Aug;97(2):439-45.
• King’s Collage Hospital Criteria
o Originally devised as prognostic criteria to predict
patient survival without liver transplant
o Now used as selection criteria for potential liver
transplant recipients
19. • Intensive care of patients with acute
liver failure: recommendations of the
U.S. Acute Liver Failure Study
Group.
Stravitz RT, Kramer AH, Davern T, Shaikh AO,
Caldwell SH et al.
Critical Care Medicine 2007; 35: 2498-508
20. • Adult U.S. Acute Liver Failure Study
Group
o Data from
23 liver transplant centers
>1,110 pts.
o In 2005 convened to
review literature on management
Care of pts. w/high ICPs
Compare practices of different centers
21. • Admit to hospital and HDU/ICU
o When evidence of ALF
E.g.: INR>1.5
o D/W:
Physician
Intensivist
Nearest transplant center
Regarding best time to refer
22. • Etiology-specific treatment
o Studies only for paracetamol overdose
o NAC regardless of time of overdose
IV if Grade I encephalopathy
Hypotension
Any other reason PO NAC is not tolerated
o HELLP or acute fatty liver of pregnancy
Tx. Is immediate delivery
23. • NAC
o 150mg/kg IV in 200ml NS over 15-60mins
o 50mg/kg IV over 4hrs
o 100mg/kg IV over 16hrs
Total dose: 300mg/kg over 20hrs
o Infusion recommended until there is
evidence of improved hepatic function
rather than time or paracetamol levels
25. • Standard treatment:
o Lactulose
Watch for:
Abdo distension
Oesophageal varices will need a scope
Avoid intravascular depletion
o Non-absorbable ATBs
Neomycin not recommended by ALFSG
because of nephrotoxicity
26. • Infection is one of main causes of death in
ALF
• Most common sites:
o Lung
o Urinary tract
o Blood
• Most common M.O.
o Gram (+) cocci: Staph aureus
o Gram (-) rods: E. coli
o Fungi: candida
27. • Empirical ATBs are recommended by ALFSG
when:
o Surveillance cultures reveal significant isolates
o Advanced stage (III/IV) encephalopathy
o Refractory hypotension
o SIRS
• 3rd gen. Cephalosporin or Timentin,
Vancomycin, Fluconazole
28. • Agitation contributes to raised ICP
• Propofol vs. Benzos
o Both increase GABA neurotransmission, therefore
may exacerbate encephalopathy
o Propofol decreases ICP and wears off quickly
• Opioids
o Shorter acting are preferable
o When there is concommitant ARF, avoid morphine
or pethidine due to metabolite accumulation
29. • Pts. with ALF are by definition coagulopathic
o Low plts. and fibrinogen, Vit. K deficient
o Spontaneous bleeding is rare
• Very difficult to obtain complete correction
• ALFSG recommends aiming for:
o INR 1.5
o Plts. 50,000
30. • Prophylactic FFP not recommended
o Obscures the trend of PT as prognostic marker
• Cryo recommended when fibrinogen low
• When FFP fails to correct PT/INR, then
recombinant factor VIIa can be given
o Should be given before planned procedures
o Avoid in patients with risk of thrombotic
complication
MI, DVTs, etc.
31. • UGI bleeding
o reduced by H2 antagonists or PPIs
• TEDS and Scuds
