Dr.

Eduardo Martinez
 Foie gras (pronounced /fwɑːˈɡrɑː/ in English; 
French for "fat liver") is a food product made
of the liver of a duck or goose that has been
specially fattened.
 Metabolic
◦ Carb metabolism
◦ Protein and lipoprotein metabolism
◦ Fatty acid metabolism
◦ Biotransformation of drugs
 Storage
◦ Glycogen
◦ Vitamins A, D, E, and K
◦ Iron and copper
 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
• 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
• ALF: Sd. defined by
o Encephalopathy
o Coagulopathy
o Jaundice
o Individual with previously normal liver
• 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.
• 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
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
• 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.
• 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
• 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
• Hepatic encephalopathy
o alteration in mental status and cognitive function
occurring in the presence of liver failure
• Liver failure leads to:
o portal HTN
o splachnic vasodilation
o Hypoalbuminaemia
o Reduced plasma oncotic pressure
o Leads to ascitis and organ oedema
• Decreased intravascular volume
o Kidneys try to “compensate” and retain Na+
and water making oedema worse
• Also,
• Gut-derived toxins reach the liver
o Ammonia levels are often high
o Correlation between ammonia and
symptoms is poor
• 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
Grade Level of Consciousness Personality and Intellect Neurologic Signs Electroencephalogram
(EEG) Abnormalities

0 Normal Normal None None

Subclini Normal Normal Abnormalities only on psychometric testing None

cal

1 Day/night sleep reversal, Forgetfulness, mild confusion, agitation, Tremor, apraxia, incoordination, impaired Triphasic waves (5 Hz)
restlessness irritability handwriting

2 Lethargy, slowed responses Disorientation to time, loss of inhibition, Asterixis, dysarthria, ataxia, hypoactive Triphasic waves (5 Hz)
inappropriate behavior reflexes

3 Somnolence, confusion Disorientation to place, aggressive behavior Asterixis, muscular rigidity, Babinski signs, Triphasic waves (5 Hz)
hyperactive reflexes

4 Coma None Decerebration Delta/slow wave activity

• 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
• 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
• 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
• 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.
• 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
• 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
• Patients with paracetamol
toxicity
o pH <7.3 (7.25 if given NAC)
Or
all three of the following:
o Prothrombin time >100s
o Serum creatinine level >300
μmol/l
o Grade III or
IVencephalopathy
• Other patients
o Prothrombin time >100
seconds or
Three of the following
variables:
o Age <10 yr or >40 yr
o Jaundice >7 days before
encephalopathy
o PT > 50s
o Bilirubin > 300mmol/L
 Positive predictive value for ICU death without
transplantation of 0.98
 Negative predictive value of 0.82
• 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
• 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
• 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
• 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
• 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
• Hepatic encephalopathy and
hyperammonaemia
• Infections
• Sedation and analgesia
• Bleeding diathesis
• Nutrition
• Seizures
• Circulatory dysfunction
• 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
• 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
• 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
• 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
• 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
• 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.
• UGI bleeding
o reduced by H2 antagonists or PPIs
• TEDS and Scuds
• ALF is a catabolic state
o Negative nitrogen balance
o Immunodeficiency
• Enteral nutrition when possible
o Hi-cal
o Avoid free water and hypo-osmolarity
• TPN when:
o Specific contraindication for enteral feeds
• Nonconvulsive seizure activity is common
o Prophylactic antiepileptics not recommended
o EEG when:
 Grade II/IV encephalopathy
 Sudden neuro deterioration
 Myoclonus
 To titrate use of barbiturates
• Tx.
o Phenytoin
o Propofol, midaz, barbiturates
• Correct hypovolaemia before starting
vasopressors
• Pressors needed for hypotension and low
CPP
o Norad is first line, can give high dose dopamine
o Adrenaline may compromise HBF
o Vasopressin not recommended because directly
causes cerebral vasodilation and high ICPs
• Medium doses of steroid may improve
pressor response
• Raised ICP due to cerebral oedema is
one of major causes of M&M
• CTB for Grade III/IV
o To rule out anything else, i.e. bleed
• ICP monitor
o Grade III/IV encephalopathy
o To optimize CPP
o Not routine
• Aim for
o ICP<25mmHg
o CPP 50-80
• General recommendations
o Keep it quiet , minimize chest physio and
ETT suctioning, head at 30o
o Don’t treat spontaneous hyperventilation,
keep PaCO2 35-40mmHg, treat fever
aggressively with physical measures
• Specific management
o Manitol: first line therapy
o Hypertonic Saline
o Induced hypothermia
o Barbiturate coma
o Indomethacin: 25mg IV over 1min.
• When to intubate:
o Respiratory failure
o Airway protection in advanced
encephalopathy
o Agitation
o Imminent ICP monitor placement
• Pts. w/ALF often develop ALI/ARDS
o Follow ARDSNet protocol
o Avoid high PEEP
 Use the minimum needed
• Indicated for:
o Renal failure
o Fluid overload
o Metabolic derangements
o Need to create space for IV colloids, i.e.
FFP
• CRRT preferred over IRRT
o HD instability common
• Use citrate over heparin
o Monitor ionized calcium
• Use bicarb buffer over lactate or citrate
buffer
o Liver won’t be able to convert them to
HCO3-
• Avoid hyponatraemia
o May exacerbate cerebral oedema
 Orthotopic liver transplant is the definitive
treatment for patients who meet the criteria
◦ or·tho·top·ic (ôrth-tpk)adj.In the normal or usual
position
 1 yr. and 5 yr . survival of patients
undergoing OLT for ALF is about 20% lower
than elective cases for cirrhotic patients
 Auxiliary liver transplantation is and

alternative
 Absolute contraindications
◦ Overwhelming sepsis
◦ Refractory hypotension
◦ AIDS
◦ Uncontrolled raised ICP with likely permanent
damange
 MARS: molecular absorption and recirculation
system
◦ Adaptation of haemodialysis
◦ Blood is dialysed against 20% albumin
 Shown to improve encephalopathy, renal function and
haemodynamic parameters
◦ The efficacy of this technique has not yet been
studied