Download Acute Liver Failure

Acute Liver Failure
Devina Bhasin, MD
Clinical Asst Professor of Medicine
Mercer University School of Medicine
Transplant Hepatologist
Piedmont Transplant Institute
Acute Liver Failure
Definition
• Rapid onset of synthetic dysfunction
– jaundice, coagulopathy, encephalopathy
• No prior liver disease
– Exceptions:
• HBV reactivation, autoimmune, Wilson’s
• Interval between jaundice and encephalopathy determines
course of disease
– < 2-6 weeks: Fulminant hepatic failure with rapid course to
recovery or death/transplant
– 2 weeks-3 months: Subfulminant hepatic failure slow
course proceeding inevitably to death/transplant
Acute Liver Failure
– Difference between rapid decompensation of
known liver disease and Acute Liver Failure
Acute Liver Failure
Normal liver
Acute liver failure
Cirrhosis
Acute Liver Failure
Grade of Encephalopathy
• Grade 0
None
• Grade 1
Day/night reversal, abnl psychometrics,
asterixis
• Grade 2
Slurred speech, + asterixis
• Grade 3
Lethargic but arousable, +/- asterixis
• Grade 4
Coma, -asterixis
Acute Liver Failure
Call the Transplant Center!
Acute Liver Failure
Etiology
• Acetaminophen (Tylenol), > 10g/day
– Can be less with chronic ETOH & malnutrition
• Idiosyncratic drug reactions (DILI)
• Viruses (hepatitis A, B, D, and E)
• Metabolic diseases (Wilson’s Disease)
• Ischemia (Budd-Chiari Syndrome)
• Autoimmune hepatitis
• Idiopathic
• Others (AFLP, HELLP syndrome, heat stroke,
infiltrative malignancy, mushroom poisoning)
Acute Liver Failure
Etiology in Adults
All other 20%
Acetaminophen 39%
HAV/HBV 11%
Unknown 17%
Idiosyncratic drugs 13%
N=308
Ann Intern Med 2002;137:947-954.
Acute Liver Failure
Things That Don’t Do It
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Hemochromatosis
Alpha-1-Antitrypsin deficiency
Cystic fibrosis
Hepatitis C (questionable case reports)
Nonalcoholic fatty liver disease (NAFLD)
Cholestatic liver diseases (PBC, PSC)
Acute Liver Failure
Outcome in U.S. Survey (1998-2001)
N=308
(17 centers)
Spontaneous
Survivors
132 (43%)
Transplanted
89 (29%)
Alive
75
Died Before
Transplant
87 (28%)
Died
14
Ann Intern Med 2002;137:947-954.
Acute Liver Failure
Demographics
APAP
Drug
(n=120) (n=40)
IND
(n=53)
Other
(n=95)
P value
Gender (%F)
79
73
60
72
NS
Age
36
41
38
43
0.02
Coma
50
43
47
47
NS
ALT
4310
574
947
1060
<0.001
Bili
4.3
20
25
13
<0.001
OLT
6
53
51
36
<0.001
Spontaneous
survival
73
25
17
33
NS
Ann Intern Med 2002;137:947-954.
Goals of First 24 Hours
• Two things to determine at initial presentation:
– Etiology
• Immediately treatable cause?
– Acetaminophen
– Autoimmune hepatitis
– Acute fatty liver of pregnancy/HELLP
• Immediately reversible cause?
– Budd-Chiari
• Futile cause?
– Wilson’s disease and FHF (mortality 100%)
– Prognosis
• Likelihood of death
• Likelihood of needing transplant
– (Transplant candidacy?)
Acute Liver Failure-Acetaminophen
Outcome
80%
75%
60%
40%
19%
20%
6%
0%
Survival
Mortality
Transplant
Acute Liver Failure
Prognosis: King’s College Criteria
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Acetaminophen induced acute liver failure
– Systemic pH < 7.30
or
– PT > 100 seconds
– Creatinine > 3.5 mg/dl
– Stage III or IV coma
Acute Liver Failure-Acetaminophen
Therapy
• Intravenous dosing of N-acetylcysteine
(Acetadose ®)
– Loading dose 150 mg/kg in 200 ml of 5% dextrose
infused over 15 minutes followed by a
maintenance dose of 50 mg/kg of 500 ml of 5%
dextrose infused over 4 hours followed by 100
mg/kg in 1000 ml of 5% dextrose infused over 16
hours.
• Oral
– Loading dose of 140 mg/kg followed by 70 mg/kg
every 4 hours to complete 17 doses.
Acute Liver Failure
Prognosis: King’s College Criteria
• Non-acetaminophen
– PT > 100 seconds
– OR any three of the following:
– PT > 50 seconds
– Age < 10 or > 40 years
– Etiology other than Hepatitis A or B
– Jaundice > 7 days before onset of encephalopathy
– Bilirubin > 17 mg/dl
Acute Liver Failure
Goals of First 24 Hours
• First Do No Harm
– Avoid sedatives or sleepers
• Interferes with prognosticators
• Will take time to metabolize
– Judicious use of factor replacement
• Interferes with prognosticators
– Avoid nephrotoxins
• aminoglycosides, CT contrast, NSAIDs
Acute Liver Failure
Initial Work-up
Key labs for prognosis
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CBC
Electrolytes with Cr
Liver enzymes
PT/INR
Factor VII activity
Factor V activity
Factor VIII activity
(control)
– Arterial pH at
presentation
– Urine/serum toxicology
screen
– Acetamenophen
– Serum alcohol screen
– Ammonia
– Lactate
– Pregnancy test
– Viral serologies
– Autoimmune markers
(include IgG)
– Ceruloplasmin
Acute Liver Failure
Initial Work-up
• Key studies for etiology
– Acetaminophen level
– HAV/HBV serologies (HAV IgM, HBcIgM)
– Ceruloplasmin (younger ages)
– ANA, SMA, Quantitative IgG
– DOPPLER ultrasound liver
– HSV (young, pregnant female)
• Additional info
– Family history
– Medications
– OTC/Herbs
Acute Liver Failure
Herbal Medications
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Jin Bu Huan
Sho-saiko-to
Ma Huang
He Shon Wu
Comfrey
Germander
Chaparral Leaf
Kava kava
Greater celandine
Hydroxycut
LipoKinetix
Comfrey
Senecio
Acute Liver Failure
Initial Work-up
• Key info for transplant candidacy
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Social history (Alcohol/drugs)
Psychiatric history (Depression/suicide attempt)
Family support
Urine tox screen
Serum alcohol
HIV test
Medical co-morbidities (morbid obesity)
Acute Liver Failure
Complications
• Renal failure
• Infectious complications
• Cerebral edema
Acute Liver Failure
Other Management Issues
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Monitor for hypoglycemia
Meticulous care of central lines
Avoid volume overload
Nutrition
Coagulopathy
Acute Liver Failure
Renal Failure
• Occurs in up to 33% of patients
• Often multifactorial:
– volume depletion, ATN, hepatorenal
• Octreotide/midodrine combination?
• Urine sodium
• Avoid CT contrast, avoid NSAIDS, empiric
aminoglycosides
• Patients tolerate volume overload poorly
– central pressure monitoring/central line
– pulmonary artery catheter
Acute Liver Failure
Infectious Complications
• 80% of patients with ALF
– Bacteremia in 20-25%
• Gut translocation & instrumentation
• Usually respiratory and urinary tract
• Gram negatives, Staph and Strep
• Fungal infection in up to 33%
• All patients should be cultured broadly with low
threshold for empiric antibiotics
• Sepsis may preclude transplant
Acute Liver Failure
Cerebral Edema
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Found in up to 80% of patients dying with FHF
Possibly due to gut derived neurotoxins leading to
vasogenic and cytotoxic edema
Arterial ammonia does correlates with degree of cerebral
edema (ammonia >150)
Difficult to diagnose with CT, thus high index of suspicion
and early monitoring essential
– Frequent neurological examination
If untreated leads to herniation and death, transplantation
the only “cure”
Acute Liver Failure
Cerebral Edema
• Classic signs of ICP elevation:
– Cushings Triad
• systemic hypertension
• Bradycardia
• irregular respirations
• Neurologic manifestations
– increased muscle tone
– hyperreflexia
– altered pupillary responses
• However, early in the course of acute liver failure, these signs
and symptoms may be absent or difficult to detect
Acute Liver Failure
Cerebral Edema
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Treatment (may buy some time)
• Mannitol
• 0.5-1.0 gm/kg
• Hyperventilation
• Elevation of head to 30 degrees
• Over-hydration can elevate ICP
• Minimizing patient agitation/stimulation
• Hypertonic Saline
• Decrease water influx into the brain and thereby
reduce cerebral edema and IC
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Na 145-155
Acute Liver Failure
• Acute, life-threatening liver injury in
previously healthy individual
• True ALF has component of hepatic
encephalopathy
• Multiple etiologies:
– APAP, other drugs, viral
– up to 1/3 are unknown cause
• Prognosis partially dependent upon etiology
• Clinical/lab criteria are imperfect for
determining outcome
Acute Liver Failure
• First 24 hours:
– Focus on immediately treatable or
reversible causes
– N-acetylcysteine for everyone
– Begin evaluation for etiology
– First do no harm: sedatives, clotting
factors, nephrotoxins, infection
– Help determine transplant candidacy
Transplant Evaluation
• Transplant Team
– Hepatologist
– Surgeon
– Physician Assistant
– Nurse coordinator
– Psychologist/Psychiatrist
– Social worker
– Dietician
– Financial Coordinator
• Affiliated consultants
– Psychiatry
– Nephrology
– Cardiology
– Pulmonology
– Anesthesiology
– Others
ELAD Liver Support System
• Extracorporeal support of
liver function
• Continuous treatment of
plasma ultrafiltrate for up
to 5 days
• Ultrafiltration Circuit +
ELAD Cartridges
ELAD Liver Support System
34
Efficacy and Safety of ELAD® in Subjects
with Acute on Chronic Hepatic Failure
(AOCH)
• Phase 2b multi-center, open-label, randomized,
concurrently-controlled subjects with AOCH
• Conducted in US and EU
• Subjects were prospectively stratified into two groups
before randomization:
• Stratum 1: Acute Alcoholic Hepatitis (AAH)
• Stratum 2: Patients with chronic liver disease,
decompensated by a precipitating event
• Randomization into Standard of Care (SOC) or ELAD
plus SOC
VTI-206 Clinical Data: AILD cohort (n=29)
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VTI-206: Phase 2b AILD Study – U.S./EU
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37 AILD subjects in predefined cohort, 26 sites
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Randomized, controlled, open-label
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90-day overall survival endpoint
Overall survival
Per Protocol Outcome
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69% overall survival on ELAD vs. 44% on control
at day 90 (p=0.27); n=29
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Median Survival: >100 days ELAD vs. 65 days
control
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No ELAD patient died after day 12
No unexpected ELAD related safety issues
From data presented at Plenary Session of 18th Congress of the ILTS (2012), by L. Teperman, MD, Chief of Transplant Surgery at NYU.
case
• 18 y/o WF admitted with abd discomfort,
malaise, fatigue for 1 week
• She was found to have abn LFTs with AST
113, ALT 85, AP 32 GGT 80 TB 7.9 INR 1.8
• Transferred to PH, TB continue to rise to
14 (> 50% indirect) with development of
HE
• Additional lab data revealed ceruloplasmin
level of 10 and other tests for ALF were
negative
Case
Acute Decompensated Wilson’s Disease
Fulminant Wilson’s Disease
Mortality without Transplant = 100%
Case
• She underwent comprehensive evaluation
for transplant and was approved
• She was listed as Status 1
• Underwent successful OLT in day 3
• She was discharged in 6 days after the
surgery
• She is now more than one year posttransplant with stable graft function
Case
• Her 24 hour urine copper 27,106 ug/24
• Hepatic quantitative copper 2241 mcg/gm
dry weight
• Explant histology revealed micronodular
cirrhosis, steatosis, cholestasis,
hepatocyte necrosis (c/w acute
decompensated wilson disease)
Case
• 28 y/o WF gravida 1 with no significant
PMH presented to her OB for her routine
visit at 37 weeks gestation
• Stable VS except BP 158/98
• 1+ pedal edema, 1+ proteinuria
• She was sent to ER for further evaluation:
Hgb 10, Plt 106, AST 290, ALT 317, LDH
371
• Working dx of HELLP (Hemolysis,
Elevated Liver enzymes Low Platelets)
syndrome was made and underwent
emergent uneventful C-section
Case
• Post-op she developed back pain and
profound hypotension, she was
transferred to ICU for resuscitation
• Lab: AST 1696, ALT 1253, LDH 1262, Plt
10K, Cr 0.8
• CT Abdomen: sub-capsular, perihepatic
hemmorage and hepatic rupture
Case
• Her platelet count dropped to 6k (nadir)
• She was treated with Plasmapheresis and
high dose corticosteroid
• She became oliguric/anuric, CRRT was
initiated
• Serologies for hepatitis A,B,C and HIV
were negative, ANA, ASMA, AMA,
ceruloplasmin were negative
• Her ABO blood type was O
Case
• Her transaminases continue to rise and
peaked >7000
• Despite aggressive therapy with steroid,
plasmapheresis, FFP, PRBC and platelets
she bacame encephalopathic and was
intubated for airway protection and
transferred to transplant center
Case
• On arrival she was unresponsive,
intubated and on pressors
• Head MRI was negative
• AST 1319, ALT 763, TB 7.6, WBC 23K, Hgb
8.4, Hct 26.6, Plt 39K, BUN 20, Cr 4.1, INR
1.5, LDH 2215, ammonia 148, lactic acid
5.1
Case
• Next few days she continued to remain
comatose with elevated transaminases,
bilirubin, INR and low factors (V and VII)
• She underwent comprehensive evaluation
for OLT and placed on the UNOS waiting
list as status 1
Case
• Transplant surgery was performed with
standard fashion using piggyback
technique
• Native liver revealed impressive hepatic
rupture with surrounding hematoma
Case
• Histology demonstrated massive hepatic
necrosis, steatosis,cholestasis and
necrotic vessels
Native Liver Explant Pathology (H&E X 40)
Native Liver Explant Pathology (H&E X 100)