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Acute Liver Failure. Dr. Eduardo Martinez. Foie Gras. 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. Functions of the Liver. Metabolic Carb metabolism

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Acute liver failure

Acute Liver Failure

Dr. Eduardo Martinez

Foie gras
Foie Gras

  • 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.

Functions of the liver
Functions of the Liver

  • Metabolic

    • Carb metabolism

    • Protein and lipoprotein metabolism

    • Fatty acid metabolism

    • Biotransformation of drugs

  • Storage

    • Glycogen

    • Vitamins A, D, E, and K

    • Iron and copper

Functions of the liver1
Functions of the Liver

  • 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

Acute liver failure


Syndrome that leads to MOF and death

Previously normal liver may fail within days

High grade encephalopathy, survival is <20%

Early death:

cerebral oedema, CVS collapse

Late death:

Sepsis , MOF

Definition and classifications

Definition and Classifications

ALF: Sd. defined by




Individual with previously normal liver

Definition and classifications1

Definition and Classifications

Fulminant Hepatic Failure

Potentially reversible condition

Consequence of severe liver injury

Encephalopathy appears within 8 wks. of initial Sx.

Absence of pre-existing liver ds.

Definition and classifications2

Definition and Classifications

King’s classification:

Hyperacute: encephalopathy within <7 days

Paracetamol, ischaemic, viral, toxins

Acute: 8-28 days

Subacute: 5-26 weeks

Seronegative, idiopathic, drug-related

Different etiology

Poorer prognosis



Agent Responsible

Viral Hepatitis

Hep. A, B, D, E, CMV, HSV, seronegative hepatitis (14-25% in UK)


Dose-related, e.g.paracetamol; idiosyncratic reactions, e.g. anti-TB, statins, recreational drugs, anticonvulsants, NSAIDs, many others


Carbon tetrachloride, amanita phalloides

Vascular events

Iscahemic hepatitis, veno-occlusive disease, Budd-Chiari, heatstroke


Pregnancy-related liver disease, Wilson’s disease, lymphoma, carcinoma, trauma




Most common causes:


Hepatotrophic viruses A-E


Paracetamol overdose

Seronegative or non-A-E hepatitis

Idiosynchratic drug rxs. or Wilson’s ds.



Identify the etiology

Hx., examination, viral and autoimmune profiles


FBC, EUC, CMP, coags, LFTs, drug levels

Abdo USG and CT

Vascular pattern, ascitis, splenomegaly



Liver Bx.

Done by transjugular route

Mays suggest specific Dx.

Watch for sample from healthy liver

>50% necrosis assoc. with poor prognosis

Need to reverse coagulopathy before doing it



Hepatic encephalopathy

alteration in mental status and cognitive function occurring in the presence of liver failure

Liver failure leads to:

portal HTN

splachnic vasodilation


Reduced plasma oncotic pressure

Leads to ascitis and organ oedema



Decreased intravascular volume

Kidneys try to “compensate” and retain Na+ and water making oedema worse


Gut-derived toxins reach the liver

Ammonia levels are often high

Correlation between ammonia and symptoms is poor

Clinical features

Clinical Features

Depend on the severity, which depends on:


Speed of onset of symptoms


N&V, abdo pain


Confusion, agitation, coma

Scale of hepatic encephalopathy

Scale Of Hepatic Encephalopathy


Level of Consciousness

Personality and Intellect

Neurologic Signs

Electroencephalogram (EEG) Abnormalities









Abnormalities only on psychometric testing



Day/night sleep reversal, restlessness

Forgetfulness, mild confusion, agitation, irritability

Tremor, apraxia, incoordination, impaired handwriting

Triphasic waves (5 Hz)


Lethargy, slowed responses

Disorientation to time, loss of inhibition, inappropriate behavior

Asterixis, dysarthria, ataxia, hypoactive reflexes

Triphasic waves (5 Hz)


Somnolence, confusion

Disorientation to place, aggressive behavior

Asterixis, muscular rigidity, Babinski signs, hyperactive reflexes

Triphasic waves (5 Hz)





Delta/slow wave activity

Clinical features1

Clinical Features

Mortality is higher for Grade III/IV

Mostly due to cerebral oedema

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

We’re now better at treating cerebral oedema

Clinical features2

Clinical Features

Elevated ICP

HTN, bradycardia, blown pupils: occur late

CTB won’t tell you

ICP monitor is best way of knowing

CVS changes

Similar to sepsis

Might be due to infection

Clinical features3

Clinical Features

Renal failure


Poor prognosis

Except with paracetamol overdose where it has a good prognosis

Impaired immunity

Decreased complement synthesis, Kupffer cell dysfunction, poor neutrophil adhesion and superoxide production

Clinical features4

Clinical Features

Increased susceptibility to infection

80% of pts. have bacteriologically proven infections

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

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

Originally devised as prognostic criteria to predict patient survival without liver transplant

Now used as selection criteria for potential liver transplant recipients

Kch criteria

KCH Criteria

  • Other patients

    • Prothrombin time >100 seconds orThree of the following variables:

    • Age <10 yr or >40 yr

    • Jaundice >7 days before encephalopathy

    • PT > 50s

    • Bilirubin > 300mmol/L

Patients with paracetamol toxicity

pH <7.3 (7.25 if given NAC)


all three of the following:

Prothrombin time >100s

Serum creatinine level >300 μmol/l

Grade III or IVencephalopathy

Kch criteria1
KCH Criteria

  • 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

Data from

23 liver transplant centers

>1,110 pts.

In 2005 convened to

review literature on management

Care of pts. w/high ICPs

Compare practices of different centers

General management

General Management

Admit to hospital and HDU/ICU

When evidence of ALF

E.g.: INR>1.5




Nearest transplant center

Regarding best time to refer

General management1

General Management

Etiology-specific treatment

Studies only for paracetamol overdose

NAC regardless of time of overdose

IV if Grade I encephalopathy


Any other reason PO NAC is not tolerated

HELLP or acute fatty liver of pregnancy

Tx. Is immediate delivery

General management2

General Management


150mg/kg IV in 200ml NS over 15-60mins

50mg/kg IV over 4hrs

100mg/kg IV over 16hrs

Total dose: 300mg/kg over 20hrs

Infusion recommended until there is evidence of improved hepatic function rather than time or paracetamol levels

Management of complications

Management of Complications

Hepatic encephalopathy and hyperammonaemia


Sedation and analgesia

Bleeding diathesis



Circulatory dysfunction



Standard treatment:


Watch for:

Abdo distension

Oesophageal varices will need a scope

Avoid intravascular depletion

Non-absorbable ATBs

Neomycin not recommended by ALFSG because of nephrotoxicity

Infection prophylaxis and surveillance

Infection prophylaxis and surveillance

Infection is one of main causes of death in ALF

Most common sites:


Urinary tract


Most common M.O.

Gram (+) cocci: Staph aureus

Gram (-) rods: E. coli

Fungi: candida

Infection prophylaxis and surveillance1

Infection prophylaxis and surveillance

Empirical ATBs are recommended by ALFSG when:

Surveillance cultures reveal significant isolates

Advanced stage (III/IV) encephalopathy

Refractory hypotension


3rd gen. Cephalosporin or Timentin, Vancomycin, Fluconazole

Sedation and analgesia

Sedation and analgesia

Agitation contributes to raised ICP

Propofol vs. Benzos

Both increase GABA neurotransmission, therefore may exacerbate encephalopathy

Propofol decreases ICP and wears off quickly


Shorter acting are preferable

When there is concommitant ARF, avoid morphine or pethidine due to metabolite accumulation

Correction of bleeding diathesis

Correction of bleeding diathesis

Pts. with ALF are by definition coagulopathic

Low plts. and fibrinogen, Vit. K deficient

Spontaneous bleeding is rare

Very difficult to obtain complete correction

ALFSG recommends aiming for:

INR 1.5

Plts. 50,000

Correction of bleeding diathesis1

Correction of bleeding diathesis

Prophylactic FFP not recommended

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

Should be given before planned procedures

Avoid in patients with risk of thrombotic complication

MI, DVTs, etc.

Correction of bleeding diathesis2

Correction of bleeding diathesis

UGI bleeding

reduced by H2 antagonists or PPIs

TEDS and Scuds



ALF is a catabolic state

Negative nitrogen balance


Enteral nutrition when possible


Avoid free water and hypo-osmolarity

TPN when:

Specific contraindication for enteral feeds

Seizure prophylaxis and surveillance

Seizure Prophylaxis and Surveillance

Nonconvulsive seizure activity is common

Prophylactic antiepileptics not recommended

EEG when:

Grade II/IV encephalopathy

Sudden neuro deterioration


To titrate use of barbiturates



Propofol, midaz, barbiturates

Cvs dysfunction

CVS Dysfunction

Correct hypovolaemia before starting vasopressors

Pressors needed for hypotension and low CPP

Norad is first line, can give high dose dopamine

Adrenaline may compromise HBF

Vasopressin not recommended because directly causes cerebral vasodilation and high ICPs

Medium doses of steroid may improve pressor response

Mx of cerebral oedema and intracranial hypertension

Mx. of Cerebral Oedema and Intracranial Hypertension

Raised ICP due to cerebral oedema is one of major causes of M&M

CTB for Grade III/IV

To rule out anything else, i.e. bleed

ICP monitor

Grade III/IV encephalopathy

To optimize CPP

Not routine

Raised icp

Raised ICP

Aim for


CPP 50-80

General recommendations

Keep it quiet , minimize chest physio and ETT suctioning, head at 30o

Don’t treat spontaneous hyperventilation, keep PaCO2 35-40mmHg, treat fever aggressively with physical measures

Raised icp1

Raised ICP

Specific management

Manitol: first line therapy

Hypertonic Saline

Induced hypothermia

Barbiturate coma

Indomethacin: 25mg IV over 1min.

Mechanical ventilation

Mechanical Ventilation

When to intubate:

Respiratory failure

Airway protection in advanced encephalopathy


Imminent ICP monitor placement

Mechanical ventilation1

Mechanical Ventilation

Pts. w/ALF often develop ALI/ARDS

Follow ARDSNet protocol

Avoid high PEEP

Use the minimum needed

Acute liver failure


Indicated for:

Renal failure

Fluid overload

Metabolic derangements

Need to create space for IV colloids, i.e. FFP

CRRT preferred over IRRT

HD instability common

Acute liver failure


Use citrate over heparin

Monitor ionized calcium

Use bicarb buffer over lactate or citrate buffer

Liver won’t be able to convert them to HCO3-

Avoid hyponatraemia

May exacerbate cerebral oedema

Liver transplant
Liver Transplant

  • 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

Liver transplant1
Liver Transplant

  • Absolute contraindications

    • Overwhelming sepsis

    • Refractory hypotension

    • AIDS

    • Uncontrolled raised ICP with likely permanent damange

Hepatic assist devices
Hepatic assist devices

  • 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