Acute Liver Failure (ALF) - Overview - Sean Caples

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Acute Liver Failure (ALF)

Overview

• Many causes of ALF

• The primary cause of death in ALF is CNS disease
(intracranial hypertension, brain herniation)

• Limited definitive treatments:

– N-acetylcysteine (NAC) in acetaminophen overdose

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Previously healthy

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61 yr old woman

• Four days of progressive confusion and fatigue
• Presented to an outside hospital

• Labs:

– Glucose 24

– AST 11,500

– ALT 12,000

– Tbili 6.1 (direct 3.8)

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• CT abd: Thickened GB wall, non-dilated bile
ducts, no stones; all else negative

• Presentation interpreted as acute cholecystitis

• Next day: cholecystectomy

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Fulminant Hepatic Failure

(Acute Liver Failure)

Defined by 3 characteristics:
1. Severe acute liver injury

2. Hepatic encephalopathy
3. Elevated PT/INR (≥ 1.5 )

<i><b>In a patient without cirrhosis or pre-existing liver disease </b></i>
<i><b>(< 26 weeks)</b></i>

<i>Hyper-acute: < 7 days</i>
<i>Acute: 7-21 days</i>

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Causes

• #1 USA/West: acetaminophen toxicity

– suicide attempt or unintentional overdose

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Other Causes

• Other viruses

– herpes simplex
– Cytomegalovirus
– Zoster

• Other drugs

– Antibiotics/anti-TB
– NSAIDs

– Anti-seizure

– Herbal supplements

• <i>Amanita </i>(mushroom)

• Autoimmune hepatitis

• Vascular

– Budd Chiari

– Ischemia/shock states
– Veno-occlusive disease

(complication of graft vs
host disease after bone
marrow transplant)

– Pregnancy

• HELLP

• Fatty liver

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This patient

• Hepatitis A serology (IgM) positive, suggesting
acute infection

• Uncommon in US, vaccine for those at-risk
(travel to endemic areas)

• Transmitted by the oral-fecal route

– well water, restaurant food, shellfish

• Usually self-limited; acute liver failure in

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Presentation

Mayo Day #1 (HD #4)

• Transferred intubated on propofol

• BP 150/80, HR 80, T 36.6C

• Exam: scattered ecchymoses

• Labs: INR 7.7, plt 160, glu corrected, creat 0.7

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That evening

• Unresponsive off propofol

• Hypertensive (SBP 180-200)

• Extensor posturing?

• Pupils equal, sluggish

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Outcomes

• The most common cause of death in acute
liver failure:

– CNS catastrophe related to vasogenic cerebral
edema and intracranial hypertension→uncal
herniation

• Prognosis/spontaneous recovery factors:

– Is the cause reversible? (APAP—N-acetylcysteine)

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Encephalopathy

<b>Grade I</b>: mild confusion, slurred speech, sleep
disturb

<b>Grade II</b>: lethargy, moderate confusion
<i>Cerebral edema: rare</i>

<b>Grade III</b>: Marked confusion, incoherent speech,
sleepy but arousable

<i>Cerebral edema: 30%</i>

<b>Grade IV</b>: coma, unresponsive, posturing

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• Management

– Typical agents used for chronic hepatic

encephalopathy are controversial and probably
not helpful in acute liver failure

• Lactulose

• Rifaximin

• Neomycin

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High intracerebral pressure (ICP)

compromises cerebral perfusion

pressure (CPP)

<b>CPP=MAP-ICP</b>

MAP= mean arterial pressure

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Intracranial pressure monitors

• Penetrate dura

• Arachnoid memb
intact

• 4% risk of
hemorrhage

• Bolt is screwed into
skull

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Methods to decrease ICP:

– HOB elevated 30 degrees to promote venous flow

– Hyperventilate to PaCO2 low 30’s

– Mannitol IV push—watch Na and serum osm,
particularly if also in renal failure

– Deeper sedation; barbiturate coma

– Unlike in ICP due to brain tumors, corticosteroids
(dexamethasone) NOT proven

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General Measures

• Proximity to a liver transplant center

• ICU setting if encephalopathy ≥ grade II
• Hemodynamics

– CPP 50-60

– MAP 65-75

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Infection

• These patients are at increased risk
• Surveillance in all patients

– Culture sputum, blood, urine, ascites

• Prophylactic antibiotics are controversial

– We give them if infection is proven or if the patient is
deteriorating

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Bleeding Risk in ALF

• The PT/INR is prognostic (MELD) but is not a reliable
indicator to trend the bleeding risk in ALF

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Management of Bleeding

• Prevention

– Vitamin K should be given

– Otherwise, prevention is controversial (unless an
invasive procedure is planned)

– No role to empirically correct PT/INR in a
non-bleeding patient

• Fresh frozen plasma/cryoprecipitate

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Factor concentrates

• Recombinant factor VIIa

– Small studies in cirrhosis; effect on bleeding
prevention unclear

– Since it’s <b>activated</b>, some (small) risk of

hypercoagulability and clotting complications

• Prothrombin complex concentrates (inactivated)

– <i>Bebulin</i>-3 Factors II, IX, X

– <i>K-centra</i>—4 factors

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N-acetylcysteine

• For acetaminophen toxicity

• Might be useful in other drug-related toxicity

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• Hepatitis B or Herpes simplex

– Antivirals (nucleos(t)ide analogues, acyclovir)

• Mushroom poisoning

– Activated charcoal binds to amatoxin

• Budd-Chiari

– Restore hepatic drainage: TIPS (transjugular

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• Wilson’s Disease

– Plasma exchange to remove copper

– No role for chelation therapy

• Autoimmune hepatitis

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Prognosis

• Degree of Encephalopathy

– Grade IV < 20% survival

• Age

– Best age 10-40

• Cause of the liver failure

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MELD-Na

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Mayo Day #2

• ICP monitor placed at 10:00 (INR 1.6 after
bebulin; increased to 5.4 later that day)

• Initial ICP: 3 mm Hg (normal > 15)

– Goal CPP = MAP – ICP of 60 mm Hg

• ICP varied from 3 to 30 throughout day

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• Extubated POD # 2

• Slowly regains cognitive function

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