acute liver failureacute liver failure definition rapid deterioration of liver function resulting in...
TRANSCRIPT
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