Acute Liver Failure (ALF) - Overview - Sean Caples

encephalopathy are controversial and probably not helpful in acute liver failure. • Lactulose[r]

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

Previously healthy

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)

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

• Presentation interpreted as acute cholecystitis

• Next day: cholecystectomy

Fulminant Hepatic Failure (Acute Liver Failure)

Defined by characteristics: Severe acute liver injury

2 Hepatic encephalopathy Elevated PT/INR (≥ 1.5 )

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

Hyper-acute: < days Acute: 7-21 days

Causes

• #1 USA/West: acetaminophen toxicity

– suicide attempt or unintentional overdose

Other Causes

• Other viruses

– herpes simplex – Cytomegalovirus – Zoster

• Other drugs

– Antibiotics/anti-TB – NSAIDs

– Anti-seizure

– Herbal supplements

• Amanita (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

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

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

That evening

• Unresponsive off propofol

• Hypertensive (SBP 180-200)

• Extensor posturing?

• Pupils equal, sluggish

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)

Encephalopathy

Grade I: mild confusion, slurred speech, sleep disturb

Grade II: lethargy, moderate confusion Cerebral edema: rare

Grade III: Marked confusion, incoherent speech, sleepy but arousable

Cerebral edema: 30%

Grade IV: coma, unresponsive, posturing

• Management

– Typical agents used for chronic hepatic

encephalopathy are controversial and probably not helpful in acute liver failure

• Lactulose

• Rifaximin

• Neomycin

High intracerebral pressure (ICP) compromises cerebral perfusion

pressure (CPP)

CPP=MAP-ICP

MAP= mean arterial pressure

Intracranial pressure monitors

• Penetrate dura

• Arachnoid memb intact

• 4% risk of hemorrhage

• Bolt is screwed into skull

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

General Measures

• Proximity to a liver transplant center • ICU setting if encephalopathy ≥ grade II • Hemodynamics

– CPP 50-60

– MAP 65-75

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

Bleeding Risk in ALF

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

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

Factor concentrates

• Recombinant factor VIIa

– Small studies in cirrhosis; effect on bleeding prevention unclear

– Since it’s activated, some (small) risk of

hypercoagulability and clotting complications

• Prothrombin complex concentrates (inactivated)

– Bebulin-3 Factors II, IX, X

– K-centra—4 factors

N-acetylcysteine

• For acetaminophen toxicity

• Might be useful in other drug-related toxicity

• 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

• Wilson’s Disease

– Plasma exchange to remove copper

– No role for chelation therapy

• Autoimmune hepatitis

Prognosis

• Degree of Encephalopathy

– Grade IV < 20% survival

• Age

– Best age 10-40

• Cause of the liver failure

MELD-Na

Mayo Day #2

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

• Initial ICP: mm Hg (normal > 15)

– Goal CPP = MAP – ICP of 60 mm Hg

• ICP varied from to 30 throughout day

• Extubated POD #

• Slowly regains cognitive function