Aliakbarian M, M.D
ACUTE LIVER FAILURE
Acute Liver Failure
Definition
Rapid deterioration of liver function
resulting in altered mentation and
coagulopathy in a patient without
preexisting cirrhosis and with an illness of
less than 26 weeks duration.
Acute Liver Failure….
• Fulminant hepatic failure
• Fulminant hepatitis
• Subfulminant liver failure
• Subacute hepatic necrosis
• Subacute liver failure
• Hyperacute liver failure
Index of Suspicion for ALF
• Clinical signs of moderate to severe hepatitis
• Laboratory findings including an increase in the prothrombin time of 4-6sec.(INR ≥ 1.5).
• Altered sensorium
INR ≥ 1.5 + Altered Mental Status = ALF
Suspect ALF?..........Admit to ICU
ALF
Etiologies
• Viral
• Drug
• Poisoning
• Ischemia
• VOD
• Malignant Infiltrate
• Wilson’s Disease
• Microvesicular
steatosis
• AIH
• Hyperthermia
• OLT
• Partial hepatectomy
Viral
• Acute Hepatitis A-E
• Reactivation of HBV
Chemotherapy
Immunosuppresion
• Herpes simplex
• Varicella-Zoster
• EBV
Acute HAV and ALF
• ALF uncommon
• Frequency 0.01% - 0.1% in
jaundiced patients
• ALF occurs early
• Survival (transplant- free) 75%
• Age related survival
Acute HBV and ALF
• HBV alone or with HDV co-infection
(rare)
• Transplant-free survival is 23%
• Overall survival 77% because of
transplantation
Drug Induced ALF
• Many drugs implicated
Acetaminophen
Halothone and derivatives
INH/ Rifampin
Tricyclics/ MAO inhibitors
Phenytoin/ NSAID
• Increased risk: acetaminophen (as little as
2gms) + ETOH median dose: 13 gm
• Increased risk if drug continued after
jaundice appears
Poisoning and ALF
• Amanita mushrooms (amanatoxins)
- LD = 50 gms (3 mushrooms)
- Toxins not destroyed by cooking
- Rapid onset of HE in 4-8 days
following severe emesis and diarrhea
• Solvents - chlorinated hydrocarbons
• Herbal remedies
• Yellow phosphorus
Obstruction of Hepatic Veins
and ALF
• Budd-Chiari syndrome
and thrombosis of hepatic
veins
• VOD - Post BMT
Chemotherapy, Irradiation
Other Etiologic Causes of ALF
• Wilson’s Disease
can be presenting feature
usually in patients <20 yrs
can occur if patient discontinued
D-penicillamine for a few years
Other Etiologies (2)
• Microvesicular steatosis
Acute fatty liver of pregnancy
Reye’s syndrome
Drug Induced - Valproic acid
• AIH
May appear as an acute hepatitis
on initial presentation
More common if anti-LKMI antibody present
ASMA usually not present
Other Etiologies (3)
• Hyperthermia (Heat stroke)
Direct thermal injury
Hepatic ischemia due to
-DIC
-Perfusion defect
• OLT
Poor presentation of donor liver
Acute graft rejection
Thrombosis - hepatic artery, hepatic
vein, portal vein
• Partial hepatectomy
Removal of 80% or more of healthy liver
Removal of 50% or less in hepatic dysfunction
Evaluation & Diagnosis
of Impending ALF
History! History! History!
Sexual contacts
IDU
Risk Factors
Pregnancy Mushrooms
Medications Travel Toxic exposures
HISTORY
• Family members with liver disease?
• Recent cold sores
• Onset of jaundice
• Work environment- toxic agents
• Hobbies
• Herbal products/dietary supplements
Physical Exam
Determine presence or absence
of pre-existing liver disease
Hepatic tenderness
Hepatic decompensation
Laboratory Tests
(1)
Drug screening
ALT, AST, Alk Phos, Glu,
Bilirubin
Lytes, Albumin, Mg, Phos.,
CBC with differential
Coags: PT, PTT
Anti HAV IgM
Anti HBc IgM/ Anti HBsAg/
Anti-HCV
Laboratory Tests
(2) If under 35 years of age
Ceruloplasmin
Serum & urine copper
Arterial blood gas
Arterial lactate
Pregnancy test
Autoimmune markers – ANA, ASMA, Ig levels
HIV status
Amylase & lipase
Liver Biopsy
Reserved for diagnostic
dilemma -
AIH, HS
(Transjugular approach)
Diagnosis of ALF
Hallmarks - occurs simultaneously or in
succession
• Altered mentation Clinical
EEG
Arterial Ammonia
• Coagulopathy
PT 4 sec prolonged (INR≥ 1.5)
• Arterial pH<7.3 if acetaminophen ingested
(cause for immediate transfer for OLT)
Management of ALF
(1)
• Directed towards prevention of complications
• ICU setting Central line(s)-10% dextrose
Pulmonary artery pressure and CO
• Inform Transplant Service and transfer with
onset of HE
• Monitor VS and urinary output (Foley)
strict I&O
• Laboratory Testing every 4-6hr electrolytes, BUN, creatinine, CBC, platelets,
PT, PTT, ALT, AST, T. bilirubin, Alk Phos, Albumin
Management (2)
• Maintain gastric pH above 5
- protonix IV
• Preparation for endotracheal intubation
• Prepare to initiate monitoring intracranial
pressure
• Enteral feeding tubes for grade 3 or 4 coma
Cerebral Edema
Cerebral Perfusion Pressure
Mean Arterial Pressure – ICP = Cerebral
Perfusion Pressure (CPP)
Ideal ICP<20-25mm Hg Ideal CPP>50-60mm Hg
Imazaki, et al
When CPP<40 for 2 hrs. 0 of 7 patients recovered
When CPP>50 6 of 8 patients recovered
Improved ICP first sign of spontaneous recovery
Management (3)
Cerebral Edema & Intracranial Hypertension
(Most serious complications of ALF)
Clinical signs of elevated ICP (Intracranial
Pressure)
-sluggish pupillary response
-increased limb-muscle tone
-none
Monitoring ICP
-usually reserved for grade 3 or 4 coma
-awaiting OLT
Management (4)
Cerebral Edema - General Measures
-quiet environment
-elevate head 10°-20°
-avoid sedation (use restraints)
-avoid Valsalva-like maneuvers
-mental status assessments q1-2h
-mannitol if signs of impending
uncal herniation (0.5mg/kg, lolus q4-8h)
when ICP<30-40mm
-assisted ventilation (in all grade 3 and 4)
Multiple Organ Failure
Hepatic damage increased risk
of infection
Failure of
clearance
Endotoxemia
Gut leak
MOF Activation of
macrophages
Tissue Circulating Release of
Hypoxia changes cytokines
TNF, IL-1, IL-6
Williams, Sem Liver Dis, Vol 16, No.4, 1996
Management (5)
Hemodynamic Complications include:
Hypotension, tachycardia, vascular volume decrease
with capillary leak and vasodilation
•Volume expansion (central line)
•FFP or 4.5% albumin, 10% dextrose
•Maintain pulmonary capillary wedge
pressure 12mm-14mm Hg
•Minimize salt solutions (ascites,
interstitial accumulation)
•Inotropic/pressor support(epi, norepi, dopamine),
but not vasopressin.
Management (6)
Coagulopathy/Bleeding Diathesis
• FFP or platelets given in presence of bleeding
• Conventional treatment of GI bleeding
• DIC thrombocytopenia
Metabolic Complications
• Prevent hypoglycemia
• Phosphate and magnesium levels
monitored - replace early
• Enteral feeding, 60gm protein/24 hrs
• No role for high branched-chain AA
• Monitor for lactic acidosis secondary to
tissue hypoxia, sepsis
Management (7)
Renal Failure
- In 42% to 82% of ALF
poor prognostic sign
- Rising creatinine and oliguria
- Metabolites of acetaminophen
are nephrotoxic leading to acute
renal failure similar to ATN and
loss of phosphate
-HRS
Additional Complications
• ARDS
• Sepsis
- Severe complement deficiency
- Decreased PMN motility
- Decreased Kupffer cell function
and removal of endotoxins
- Increased levels of TNF and IL-6
Prognostic Factors
• Dependent on Etiology
• Younger patients do better (<40 and >10)
• Presence of cerebral edema
• Delay between jaundice and HE of more
than 3 weeks - poorer prognosis
• MOF - poor prognosis
Current Treatment
Transplantation
OUTCOME RESULTS U.S. ALF
STUDY GROUP
308 Patients
Spontaneous
Survivors
n=132
(43%)
Transplanted
N=89
(29%)
Died before
Transplantation
n=87
(28%)
Transplanted
N=89
(29%)
Alive
N=75
(84%)
Died
N=14
(16%)
Approach to Suspected ALF
• Etiology and Pathogenesis
• Evaluation and Diagnosis
• Complications
• Management
• Prognosis
• Current and future treatment
approaches