Transcript כרמלי-חגי צ. התקלקלות בלתי מסבלת של הכבד(Fulminant hepatic failure)

‫ההתקלקלות הבלתי‬
‫נסבלת של הכבד‬
‫מיכל כרמיאל‪-‬חגי‬
‫מנהלת השרות להשתלת כבד‬
‫המכון למחלות דרכי העיכול והכבד‬
‫המרכז הרפואי 'סוראסקי'‬
‫תל‪-‬אביב‬
‫פרטי המקרה‬
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‫בת ‪ 38‬ילידת הארץ ממוצא דרוזי‪ ,‬נ‪4+‬‬
‫‪ : 6.2003‬כאב בטן טרנסאמינזות מוגברות וצהבת‬
‫סרולוגיה ויראלית – שלילית‬
‫סרולוגיה אימונית – שלילית‬
‫ברור למחלת וילסון‪ ,‬חסר ‪,A1AT‬‬
‫הדמיה – א‪.‬מ‪.‬ל‬
‫ביופסית כבד‪AIH VS TOXIC HEPATITIS :‬‬
‫‪ :Rx‬פרדניזון‬
‫פרטי המקרה‬
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‫‪ :3/7‬אישפוז בשל עירפול הכרה והחמרה בתפקודי‬
‫הכבד והקרישה‬
‫‪ :4/7‬מועברת לטנ"מ איכילוב מורדמת‪ ,‬מונשמת‬
‫• יציבה המודינמית‪ ,‬הנשמה‪ SIMV :‬מחמצנת היטב‬
‫• אישונים שווים ומגיבים‪ ,‬ללא החזרים פתולוגים‬
‫• בדיקה גופנית תקינה למעט צהבת‪ ,‬כבד נמוש מוגדל‪,‬‬
‫מיימת גבולית‬
‫•ס‪.‬ד טרומבוציטופניה ולויקוציטוזיס‬
‫• טרנסאמינזות באלפים‪ ,‬בילירובין ‪27 mg/dL>- 14.0mg/dL‬‬
‫•‪( 4.9>- 2.0 : INR‬פקטור ‪)12.5% V‬‬
‫• קראטינין ‪ 0.55‬אמוניה ‪212 micg/dL‬‬
‫• ‪ Ph 7.31; Lactate 3.3 mmol/L‬גלוקוז ‪)glucse drip( 70‬‬
‫פרטי המקרה‬
‫ ללא לחץ על חדרי המח‬,‫ ללא דימום‬:‫ ראש‬CT
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Intracranial pressure monitoring: Bolt •
‫• הנשמה‬
‫• סדציה מינימלית‬
IV Glucose drip / Fluids •
IV N-Acetyl Cystein •
IV Manitol •
1 ‫• רישום להשתלה – סטטוס‬
Antibiotic •
‫• חיפוש תורם מהחי‬
MARS •
FULMINANT LIVER
FAILURE
DEFINITION
 <8
week of signs and symptoms
 No H/O chronic liver disease
• Coagulopathy
• Encephalopathy
Fuliminant
Liver
Failure
Severe
AcuteAcute
Hepatitis
Hepatitis
Definition

Fulminant Hepatic Failure (FHF):
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
Encephalopathy with jaundice
Severely reduced synthetic function (INR)
Hyper Acute:
Encephalopathy
< 7 days after
onset of Jaundice
Acute:
Encephalopathy
< 28 days after
onset of Jaundice
Sub Acute:
Encephalopathy
< 3 months after
onset of disease
Fulminant Hepatitis
Normal Liver
Etiology
HBV
HBV+HDV
HAV
non A-E
Herpes
Drugs
Toxic
Other
8%
6%
2%
1%
Female= 73%
Median age = 38
25%
4%
40%
14%
France 1988-1993
USA 1998-2002
Acetaminophen
Drugs
HAV+HBV
non A-E
Other
19%
39%
17%
12%
13%
Survival in FHF
Ostapowicz G et al Ann Intern Med. 2002
Clinical Presentation:
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Hepatocellular dysfunction
Encephalopathy and cerebral edema
Infections
Multiple organ failure: HD, Respiratory, GI,
Kidney

Death
Clinical Presentation:
Hepatocellular Dysfunction

Impaired elimination of bilirubin
• Poor synthetic function:
•
Factors I, II, V, VII, IX, X
Diminished gluconeogenesis:
Hypoglycemia
• Decreased lactate up-take+increased
intracellular lactate: metabolic acidosis
Clinical Presentation:
Brain
edema
FHF
ALF
Minimal
Chronic
Encephalopathy
Acute
CIRRHOSIS
Brain
edema
Clinical Presentation:
Cytockines:
Others:
Amonia
Glutamine
Glutamate
TNFA
•GABAr?
•Monoamines?
• CO2
Liver
Failure
Neurotoxins:
Renal
Failure
Infection
Encephalopathy - Pathophysiology
Necrosis
Clinical Presentation:
Encephalopathy - Pathophysiology
Neurotoxins:
Cytockines:
Others:
Amonia
Glutamine
Glutamate
TNFA
•GABAr?
•Monoamines?
• CO2
Cytogenic Effect
Vasogenic Effect
Cerebral Edma
Hepatic Encephalopathy and
Cerebral Edema:
Stage
I
Symptoms
Signs
Stage
II
Stage
III
Insomnia
Difficulties in
concentration
Drowsiness
confusion
Somnolence
Sluggish
speech
Flapping
tremor
Flapping
tremor
Stage
IV
Coma
Brain
Edema
Coma
ICP HTN
Convulsions
Herniation
Death
Encephalopathy
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Treat any reversible condition
Sedation/relaxation/ventilation
Hyperventilation
Imaging
ICP monitoring
Medication:
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Osmotherapy
Barbiturate
 Lactulos Rx. – No benefit
Irritation prevention
MARS
The MARS®
MARS - Indications:
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Acute Liver Failure:
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Increased ICP
Alcoholic hepatitis
Intoxication
Autoimmune
Wilson crises
Renal failure
Reduction of ICP during
MARS treatment
ICP (mmHg)
24
22
20
18
16
14
12
10
8
6
Before
During
After
Sorkine et al.
Bridging for transplant
Crit Care Med 2001
Infection
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Up to 80% of pts.:
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Bacteremia in 25% of pts.
Fungal infection in 30%
Pathophysiology:
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Impaired neutrophil function
Damaged hepatic macrophages
Invasive procedures
Infection
High index of suspicious
 Low threshold for Abs. Rx.
 Surveillance culturing
 Prophylaxis – controversial
 Enteral decontamination
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Multiple Organ Failure Syndrome
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Peripheral vasodilatation
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MAP >60 mm Hg
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Ventilation
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Renal failure:
(hypotension)
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Respiratory failure
(pulmonary edema vs. ARDS)
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Acute tubular necrosis
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DIC
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Hemofiltration
MARS
‫באדיבות ד"ר נמרוד עדי‪ ,‬ט"נ‬
Outcome
Predictors:
Overall transplantfree
survival =18- 33%
Clinical
Age
Encephalopathy
Etiology
ICP
Lab. test
Bilirubin
Creatinine
INR, factor V
Lactate
Phosphate
AFP
Favorable
Unfavorable
ACAP intoxication
 HAV
 AFLP
 Shock liver

Valine
Idiopathic
 Drugs (not
ACPA)
 HBV
 Other
pH
Cholinesterase

MELD score
Physiological
APACHE II
Histological
Degree of necrosis
Morphological
Liver volume
Criteria of King’s College, London
Acetamonophen Patients:
• Arterial pH<7.3, or
• INR>6.5 + Serum creatinine > 3.4
Non-acetaminophen Patients:
• INR >6.5 , or
Factor V <20% < age 30 yr,
or
Factor V <30% > age 30yr
Hospital Paul-Brousse
Any three of the following:
• Age <10 yr or >40
• Etiology: non A, non B, halothane hepatitis, idiosyncratic drug reaction
• Duration of jaundice before encephalopathy > 7 days
• INR > 3.5
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
No
Liver Transplantation
Yes
Ongoing intensive care
Fulminant Hepatic Failure in
TASMC 4/2000 – 10/2005



38 Pts. (M:F = 18:20)
Median age of 39 Y/O (14.5-70)
27/40 referrals with liver failure had FHF
Etiology of FHF in TASMC 2000-2005
HBV
Idiopathic
Drugs
ACAP
Mashroom
Wilson
Other
11%
8%
8%
16%
18%
21%
18%
Liver Transplantation for FHF
TASMC 4/2000 – 10/2005
22/38 (57%) where listed for Tx.
Median age: 33 y/o (range: 15-61)
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Transplanted: 15;
Recovered w/o Tx: 4;
Died w/o Tx: 3
17/38 where not listed
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Not eligible: 9 (M=64 y/o) 100% mortality
Not indicated: 7 (M=49 y/o) 100% recovery
Outcome of Liver Transplantation
Due to FHF
TASMC 2000-2005



11/15 Urgent LTx (CD:LDLT = 6 : 5)
Median F/U of 19 months (6.7-62 m)
One year graft survival: 67%
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

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Cadaveric Tx = 40%
Living donor = 100%
One year patient survival = 78%
Cause of death:


Primary graft non-function
Sepsis
Outcome of Patients with FHF
According to Etiology
TASMC 2000-2005
8
Diead no Tx
4
Liver Tx
2
Alive no TX
H
B
Id
V
io
pa
th
ic
s
ru
g
D
P
A
C
A
O
th
er
W
il s
M
on
as
hr
oo
m
0
n=38
6
‫תודה‬