1. Diagnostic m eth ods of liver dis eas e s2. Typical ch ange s of enzym e activitie s in m ajor type s of liver dis eas e s3. Alcoh ol induced liver dis eas e s4. A com parison of different viral h epatitis type s5. H epatitis A6. Serological ch ange s in h epatitis B: s e roconvers ion7. Serological ch ange s in h epatitis B: no s e roconvers ion8. Norm al bilirubin m etabolism9 . Norm al and elevated bilirubin levels10. Clas s ification of unconjugated and conjugated h yperbilirubinem ias11. H em olytic jaundice12. O bstructive jaundice13. H epatocellular jaundice14. Serum and urine bilirubin, and urine UBG levels in acute viral h epatitis15. Th e differential diagnos is of jaundice

Laboratory evaluation of liver d isease s

Diagnostic m eth ods of liver d isease s

• Ph ys ical exam inationTh e color of th e s k in, urine and fece s , oth e r clinical sym ptom s

• Enzym e diagnosticsM easuring th e activity of enzym e s getting into th e plasm a in parench ym al necros is (ASAT, ALAT) and in biliary obstruction (ALP, GGT)

• Evaluation of th e conjugation-excretion functionSerum bilirubin fractions , urine bilirubin, urine UBG, fecal UBG, fasting s e rum bile acids

• Evaluation of th e s ynth etic function of th e liverAlbum in, m any clotting factors , som e globulins , ps eudoch oline steras e , proth rom bin tim e

• M icrobiological/im m unological te stsH BSAg etc.

• Plasm a levels of oth er m aterialsNH 4

+ , Fe, Cu, ch olesterol, LP-X, AFP, CEA

• Im aging m eth odsultrasound, rtg, ERCP, PTC, CT, MRI

• Liver biopsy

1

Typical ch anges of enzym e activitie s in m ajor types of liver d isease s

Acute viralh epatitis (A)

Acute alcoh olich epatitis

Biliary obstruction

jaundice biliary colic

[w e e k s] [w e e k s] [days]

Enzy

me

activ

ity in

pla

sma

[U/l]

ALAT ASAT GGT ALP

1 2 3 4 5 6 1 2 3 4 5 60 1 2 3 4 5 600

200

400

600

800

1000

1200

2

Fatty liverAcute

alcoh olich epatitis

Cirrh os is

recurrence

revers ible irrevers ible

s everity of th e dis eas e

Alcoh ol induced liver d isease s 3

Com parison of different h epatitis types

VirusIncubation tim e (m ean)

O ns et

Typical route of infection

Ch ronic h epatitis

Prevention

Typical clinical cours e

H BV1– 6 m onth s

(2– 3)slow or acute

parenteral, s exual

rare (1– 10%)

none

som etim e s s evere

H AV2– 6

w e e k s (4)

acute

fecal-oral

never

IG, vaccine

m ild

IG, vaccine

H CVh alf– 6

m onth s (2)

slow

parenteral

very com m on

(cca. 50%)

average

H DV1– 6 m onth s

(2– 3)

slow or acute

parenteral, s exual

com m on

som etim e s s evere

H BV vaccine

none

never

m ild

fecal-oral (th rough w ater)

acute

2– 8 w e e k s (6)

H EV

Th e oth er h epatotropic virus e s (F, G) identified don't s e em to be clinically im portant.

4

H epatitis A

H AV in fece s

anti-H AV total

anti-H AV IgM

clinical sym ptom s

ALATbilirubin

tim e s ince th e infection[days]

ALA

T [U

/l]H

AV a

ntig

en in

fece

s [cp

m]

anti-HAV

[relative conc.]

bilirubin [µmol/l]

2000

1000

1000800600400200

010 20 30 40 50 60 70 80 9 0 100

80604020

5

Serological ch anges in h epatitis B:norm al seroconversion

tim e

sym ptom s

H BSAganti-H BS

H BeAg

anti-H Be

anti-H Bc-total

anti-H Bc-IgM

core -w indow

incubationno sym ptom s(4– 12 w e e k s)

acuteinfection

(2– 12 w e e k s)

recentacute infection(2– 26 w e e k s)

dis eas e -fre estate

(years)

[rela

tive

conc

entra

tion]

6

H BSAg

H BeAg

anti-H Bc-totalanti-H Bc-IgM

tim e

incubationno sym ptom s(4– 12 w e e k s)

acuteinfection

(6 m onth s)

ch ronicinfection(years)

[rela

tive

conc

entra

tion]

Serological ch anges in h epatitis B:no seroconversion

7

Norm al bilirubin m etabolism

Kidney

liver cell

GI tract

fece s

blood ve s s el

urine : UBG norm .

enteroh epatic circulation

RBC

RES

h em eglobin

ironncB

H b

ncB ncB cB

albu-m in cB

UBG

stercobilin urobilin

UBG

UBG

8

Norm al and elevated bilirubin levels

h yperbilirubinaem ianorm alindirect

norm

alhy

perb

iliru

bina

emiaicte

rus

subi

cter

us

direct

50

17

direct Bi < 5 µm ol/l direct directtotal Bi < 17 µm ol/l total total< 0,2 ≥ 0,4

seru

m b

iliru

bin

leve

l (to

tal)

[µm

ol/l]

9

h em olys is , increas ed ineffective eryth ropoie s is

Clas s ification of unconjugated és conjugated h yperbilirubinem ias

Pre h epatic:(increas ed bilirubin production)

I.

II. H epatic:im paired bilirubin uptak e

Gilbert-dis eas e com petition

a)

b) im paired conjugation

Gilbert-dis eas eCrigler-Najjar sy. I, IIph ys iological jaundice of new borns

no s ign of h em olys is

no s ign of h epatic le s ion

c)

d)

im paired excretion

Dubin-Joh nson sy.Rotor sy.ch olestas is in pregnancybenign recurrent ch olestas is

s igns of m ild obstructive jaundice

s igns of m ild

obstruction

s igns of h epatic le s ion

III.

com bined abnorm .(h epatocellular inflam m ation)

h epatitis : viraloth er m icrobe s , toxic dam age s , cirrh os is

Posth epatic:(biliary obstruction)a) intrah epaticb) exrah epatic

s igns of obstruction

s igns of m ild h epatic le s ion

prim ary biliary cirrh os isdrug induced, bile stone , tum or

10

H em olytic jaundice

Kidney

liver cell

GI tract

fece s : pleioch rom ic

blood ve s s el

urine : UBG ↑

enteroh epatic circulation

RBC

RES

ncB ncB cB

albu-m in cB

UBG

stercobilin urobilin

UBG

UBG

11

O bstructive jaundice

Kidney

liver cell

GI tract

fece s : ach olic

blood ve s s el

urine : UBG negativebilirubin (conjugated) pos itive

RBC

RES

ncB ncB cB

albu-m in

cB

cB

cB

12

H epatocellular jaundice

Kidney

liver cell

GI tract

fece s : ligh t colored

blood ve s s el

urine : UBG ↑bilirubin (conjugated) pos itive

RBC

RES

ncB ncB cB

albu-m in cB

UBG

stercobilin urobilin

UBG

UBG

cB

cB

13

s e rum bilirubin

urine bilirubin

urine UBG[rela

tive

units

]

[w e e k s]1 2 3 4 5 6 7 8

Serum and urine b ilirubin, and urine UBG levels in acute viral h epatitis

14

Th e d ifferential diagnosis of jaundice

Serum

Urine

Stool

Serum

O th er

Pre h epatic(h em olys is)

H epatic(h epatitis)

Posth epatic(obstruction)

unconjugated bilirubin

conjugated bilirubinconjugated bilirubin

UBGUBGLDH

ASAT, ALATALP, GGT

FeCh olesterol

↑

N, ↑–

↑↑↑↑

LDH 1 ↑NN↑

N

↑

↑+

↑↓

LDH 5 ↑↑↑↑↑

N, ↓

↑

↑↑+

↓ –↓ –N

↑↑↑N

↑

h aptoglobin: ↓reticulocyte : ↑

INR: ↑After vitam in K:

no ch ange

INR: ↑After vitam in K:

N

N: norm al value, or th e ch ange is not typical– : cannot be detected+ : can be detected

15