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Diagnostik und Monitoring der Leberfunktion Diagnostik und ...

Diagnostik und Monitoring der

Leberfunktion

Laboratoriumsdiagnostik in der Intensivmedizin

USZ 15.5.2009

Beat Müllhaupt

Klinik für Gastroenterologie und Hepatologie

Universitätsspital Zürich/Swiss HPB Center

BM 11.5.2009 ICU Labordiagnostik 2009 1


Liver Function

Scores:

Child-Pugh Score

Meld-Score

Disease specific scores

BM 11.5.2009 ICU Labordiagnostik 2009 2


Diagnostik und Monitoring

der Leberfunktion

• Primary Liver Disease

– Acute liver failure

– (Acute-on-)chronic liver failure

– After liver surgery

• Primary Disease of other Organ(s)

– Decompensation of preexisting liver disease

(e.g. after extrahepatic surgery)

– De-novo liver dysfunction (e.g. sepsis)

BM 11.5.2009 ICU Labordiagnostik 2009 3


Diagnostik und Monitoring

der Leberfunktion

• Primary Liver Disease

– Acute liver failure

– (Acute-on-)chronic liver failure

– After liver surgery

• Primary Disease of other Organ(s)

– Decompensation of preexisting liver disease

(e.g. after extrahepatic surgery)

– De-novo liver dysfunction (e.g. sepsis)

BM 11.5.2009 ICU Labordiagnostik 2009 4


Liver failure

100%

Acute Hepatic Failure (5%)

Liver function

Acute on Chronic

Hepatic Failure (95%)

UNOS 1

UNOS 2B

UNOS 2A

Chronic liver failure

Time up to >15 years

BM 11.5.2009 ICU Labordiagnostik 2009 5


Acute liver failure

• INR > 1.5 + encephalopathy w/o preexisting

liver disease

• Duration of less than 26 weeks

• Exceptions in spite on the possibility of

cirrhosis:

• Wilson‘s disease

• Vertically acquired hepatitis B

• Autoimmune hepatitis

If disease known


Dilemma of OLT in ALF

Liver

Function

Window

for OLT

Need for prognostic scores

Survival

• with Referral

OLT

• Listing

?

Natural

critical

History

limit for

survival

Time

BM 11.5.2009 ICU Labordiagnostik 2009 7


Referral to transplant center

1. Patients with ALF should be admitted and

monitored frequently, preferably in an ICU (III).

2. Contact with a transplant center and plans to

transfer appropriate patients with ALF should be

initiated early (HE I-II) in the evaluation process

(III).

Polson et al Hepatology 2005;41:1179-1187

BM 11.5.2009 ICU Labordiagnostik 2009 8


Kings College Criteria for SU

Listing

Non-Paracetamol

PTT (INR) > 6.5

or

>3 of following

– Age 40 yrs.

– Drug-induced/NANB

– Jaundice >7d prior E

– INR > 3.5

– Bilirubin >300 umol/l

Paracetamol

pH 6.5

– Crea >300 umol/l

– Encephalopathy 3/4

O‘Grady et al Gastroenterology 1989;97: 439-445

BM 11.5.2009 ICU Labordiagnostik 2009 9


Kings College Criteria for SU

Listing

Survival w/o OLT

Paracetamol

Pooled Sens 8 studies % (95%CI) 69 (63-75)

Pooled Spec 8 studies % (95%CI) 92 (81-97)

Bailey et et al al Crit Care Med 2003;31:299-305

305

(range)

PPV % (range) NPV % (range) PA %

Paracetamol 73-84

71-94

72-92

Non-Para

68-98

25-82

61-94

Riordan et et al al Sem Liver Dis 2003;23:203-215

215

BM 11.5.2009 ICU Labordiagnostik 2009 10


Modified Kings Criteria

for Paracetamol

Lactat

1. Strongly consider listing

• Lactate >3.5 after early fluid resuscitation

2. List for transplantation if:

• pH 3.0

or

• Serum Krea >300umol/l, INR>6.5 and

HE Grad III-IV

Bernal et al Lancet 2002:359;558-63

BM 11.5.2009 ICU Labordiagnostik 2009 11


Clichy Criteria for SU Listing

Age 30 yrs.

Faktor V


Clichy Criteria for SU

Listing

Recommendation 44.

Currently available prognostic scoring systems

Sens Spez Acc

do not adequately predict outcome and determine


Diagnostik und Monitoring

der Leberfunktion

• Primary Liver Disease

– Acute liver failure

– (Acute-on-)chronic liver failure

– After liver surgery

• Primary Disease of other Organ(s)

– Decompensation of preexisting liver disease

(e.g. after extrahepatic surgery)

– De-novo liver dysfunction (e.g. sepsis)

BM 11.5.2009 ICU Labordiagnostik 2009 14


Prognosis

• Liver function test

• Child-Pugh Score, MELD

• Dynamic tests etc

• Disease specific score

• PBC Risko score

BM 11.5.2009 ICU Labordiagnostik 2009 15


Child-Pugh Classification

of Cirrhosis

Points 1 2 3

Albumin (g/l) > 35 28 - 35 < 28

Bilirubin (µmol/l) < 34 34 - 51 > 51

Quick(%)/INR > 70/2.2

Ascites none mild tense

Encephalopathy none I - II III - V

A: 5-6 Points compensated cirrhosis

B: 7-9 Points decompensated cirrhosis

C: 10-15 Points decompensated cirrhosis

BM 11.5.2009 ICU Labordiagnostik 2009 16


Decompensation

Compensated cirrhosis

Decompensated cirrhosis

5 yrs survival = 80 %

Median Survival = 24-48 months

Fattovich et al Am J Gastroenterol 2002;2886-95

BM 11.5.2009 ICU Labordiagnostik 2009 17


MELD-Score

MELD score =

9.57×log Krea mg/dL+

3.78×log Bili mg/dL+

11.20xlog INR +

6.43

http://www.optn.org/resources/meldPeldCalculator.asp

BM 11.5.2009 ICU Labordiagnostik 2009 18


60

MELD vs Child

50

MELD Score

40

30

20

10

0

CTP Score

r=0.66; p


MELD vs Child

Sensitivity

1

0.8

0.6

0.4

0.2

0

MELD AUC =0.83

CTP AUC = 0.76

Survival 3 mo (%)

100%

80%

60%

40%

20%

0%

0 0.2 0.4 0.6 0.8 1

0 20 40 60

1-Specificity

Severity Score

Wiesner et al Gastroenterology 2003:124:91-6

BM 11.5.2009 ICU Labordiagnostik 2009 20


Survival benefit

Merion et al Am J Transplantation 2005;5:307-13

BM 11.5.2009 ICU Labordiagnostik 2009 21


Diagnostik und Monitoring

der Leberfunktion

• Primary Liver Disease

– Acute liver failure

– (Acute-on-)chronic liver failure

– After liver surgery

• Primary Disease of other Organ(s)

– Decompensation of preexisting liver disease

(e.g. after extrahepatic surgery)

– De-novo liver dysfunction (e.g. sepsis)

BM 11.5.2009 ICU Labordiagnostik 2009 22


Inflammation and the liver

BM 11.5.2009 ICU Labordiagnostik 2009 23


Inflammation and Jaundice

BS - Bsep

MRP3,4

TNF

IL-1

IL-6

Trauner N Engl J Med 1998

BM 11.5.2009 ICU Labordiagnostik 2009 Geier & Trauner BBA 2006 24


Diagnostik und Monitoring

der Leberfunktion

• Primary Liver Disease

– Acute liver failure

• Clichy

– (Acute-on-)chronic liver failure

• MELD

– After liver surgery

• 50-50 rule

• Primary Disease of other Organ(s)

– Decompensation of preexisting liver disease (e.g.

after extrahepatic surgery)

• MELD

– De-novo liver dysfunction (e.g. sepsis)

BM 11.5.2009 ICU Labordiagnostik 2009 25

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