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1
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???? ??????-??? ????? ????? ?????? ??? ?????
?????? ???? ?????? ????? ????? ??????
'???????' ??-????
2
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• ?? 38 ????? ???? ????? ?????, ?4
• 6.2003 ??? ??? ??????????? ??????? ?????
• ???????? ??????? ??????
• ???????? ??????? ??????
• ???? ????? ??????, ??? A1AT,
• ????? ?.?.?
• ??????? ??? AIH VS TOXIC HEPATITIS
• Rx ????????

3
???? ?????

• 3/7 ?????? ??? ?????? ???? ?????? ??????? ????
  ???????
• 4/7 ?????? ???"? ???????

??????, ??????

• ????? ?????????, ????? SIMV ?????? ????
• ??????? ????? ???????, ??? ?????? ????????
• ????? ?????? ????? ???? ????, ??? ???? ?????,
• ????? ??????

• ?.? ?????????????? ?????????????
• ??????????? ??????, ????????? 14.0mg/dL -gt27
  mg/dL
• INR 2.0 -gt4.9 (????? V 12.5)
• ???????? 0.55 ?????? 212 micg/dL
• Ph 7.31 Lactate 3.3 mmol/L ?????? 70 (glucse
  drip)

4
???? ?????

• CT ??? ??? ?????, ??? ??? ?? ???? ???

• Intracranial pressure monitoring Bolt

• ?????
• ????? ????????
• IV Glucose drip / Fluids
• IV N-Acetyl Cystein
• IV Manitol
• Antibiotic
• MARS

• ????? ?????? ????? 1
• ????? ???? ????

5
FULMINANT LIVER FAILURE
6
DEFINITION

• lt8 week of signs and symptoms
• No H/O chronic liver disease

• Coagulopathy

• Encephalopathy

Fuliminant Liver Failure
Acute Hepatitis
Severe Acute Hepatitis
7
Definition

• Fulminant Hepatic Failure (FHF)
• Encephalopathy with jaundice
• Severely reduced synthetic function (INR)

Hyper Acute Encephalopathy lt 7 days after onset
of Jaundice
Acute Encephalopathy lt 28 days after onset of
Jaundice
Sub Acute Encephalopathy lt 3 months after onset
of disease
8
Normal Liver
Fulminant Hepatitis
9
Etiology
Female 73 Median age 38
France 1988-1993
USA 1998-2002
10
Survival in FHF
Ostapowicz G et al Ann Intern Med. 2002
11
Clinical Presentation

• Hepatocellular dysfunction
• Encephalopathy and cerebral edema
• Infections
• Multiple organ failure HD, Respiratory, GI,
  Kidney
• Death

12
Clinical Presentation Hepatocellular Dysfunction

• Impaired elimination of bilirubin

• Poor synthetic function Factors I,
  II, V, VII, IX, X

• Diminished gluconeogenesis
• Hypoglycemia

• Decreased lactate up-takeincreased
• intracellular lactate metabolic acidosis

13
Clinical Presentation Encephalopathy
Chronic
Brain edema
Brain edema
Minimal
FHF
Acute
ALF CIRRHOSIS
14
Clinical Presentation Encephalopathy -
Pathophysiology
Neurotoxins Amonia Glutamine Glutamate

• Others
• GABAr?
• Monoamines?
• CO2

Cytockines TNFA
Liver Failure
Infection
Renal Failure
Necrosis
15
Clinical Presentation Encephalopathy -
Pathophysiology

• Others
• GABAr?
• Monoamines?
• CO2

Cytockines TNFA
Neurotoxins Amonia Glutamine Glutamate
Cytogenic Effect
Vasogenic Effect
Cerebral Edma
16
Hepatic Encephalopathy and Cerebral Edema
Stage I Stage II Stage III Stage IV Brain Edema
Symptoms Insomnia Difficulties in concentration Drowsiness confusion Somnolence Coma Coma ICP HTN Convulsions Herniation Death
Signs Sluggish speech Flapping tremor Flapping tremor Coma Coma ICP HTN Convulsions Herniation Death
17
Encephalopathy

• Treat any reversible condition
• Sedation/relaxation/ventilation
• Hyperventilation
• Imaging
• ICP monitoring
• Medication
• Osmotherapy
• Barbiturate
• Irritation prevention
• MARS

• Lactulos Rx. No benefit

18
The MARS
19
MARS - Indications

• Acute Liver Failure
• Increased ICP
• Alcoholic hepatitis
• Intoxication
• Autoimmune
• Wilson crises
• Renal failure

Reduction of ICP during MARS treatment
Sorkine et al. Crit Care Med 2001
Bridging for transplant
20
Infection

• Up to 80 of pts.
• Bacteremia in 25 of pts.
• Fungal infection in 30
• Pathophysiology
• Impaired neutrophil function
• Damaged hepatic macrophages
• Invasive procedures

21
Infection

• High index of suspicious
• Low threshold for Abs. Rx.
• Surveillance culturing
• Prophylaxis controversial
• Enteral decontamination

22
Multiple Organ Failure Syndrome

• Peripheral vasodilatation (hypotension)
• Respiratory failure (pulmonary edema vs. ARDS)
• Acute tubular necrosis
• DIC

• MAP gt60 mm Hg
• Ventilation
• Renal failure
• Hemofiltration
• MARS

23
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24
OutcomePredictors
Clinical Age
Encephalopathy
Etiology
ICP
Lab. test Bilirubin
Creatinine
INR, factor V
Lactate
Phosphate
AFP
Valine
pH
Cholinesterase
MELD score
Physiological APACHE II
Histological Degree of necrosis
Morphological Liver volume
Overall transplant-free survival 18-33

• Favorable
• ACAP intoxication
• HAV
• AFLP
• Shock liver

• Unfavorable
• Idiopathic
• Drugs (not ACPA)
• HBV
• Other

25
Criteria of Kings College, London

• Acetamonophen Patients
• Arterial pHlt7.3, or
• INRgt6.5 Serum creatinine gt 3.4
• Non-acetaminophen Patients
• INR gt6.5 , or
• Any three of the following
• Age lt10 yr or gt40
• Etiology non A, non B, halothane hepatitis,
  idiosyncratic drug reaction
• Duration of jaundice before encephalopathy gt 7
  days
• INR gt 3.5

Factor V lt20 lt age 30 yr, or Factor V lt30 gt
age 30yr Hospital Paul-Brousse
26
Management
Intensive care Etiology specific
Rx. Consultation with LTx center
Yes
Contraindication for Tx
Continue intensive support
No
Transfer to LTx center National status one
Re-assess for recovery or contraindication for LTx
Yes
Ongoing intensive care
No
Liver Transplantation
27
Fulminant Hepatic Failure inTASMC 4/2000
10/2005

• 38 Pts. (MF 1820)
• Median age of 39 Y/O (14.5-70)
• 27/40 referrals with liver failure had FHF

28
Liver Transplantation for FHFTASMC 4/2000
10/2005

• 22/38 (57) where listed for Tx.
• Median age 33 y/o (range 15-61)
• Transplanted 15
• Recovered w/o Tx 4
• Died w/o Tx 3
• 17/38 where not listed
• Not eligible 9 (M64 y/o) 100 mortality
• Not indicated 7 (M49 y/o) 100 recovery

29
Outcome of Liver Transplantation Due to FHF
TASMC 2000-2005

• 11/15 Urgent LTx (CDLDLT 6 5)
• Median F/U of 19 months (6.7-62 m)
• One year graft survival 67
• Cadaveric Tx 40
• Living donor 100
• One year patient survival 78
• Cause of death
• Primary graft non-function
• Sepsis

30
Outcome of Patients with FHF According to
Etiology TASMC 2000-2005
31
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