Pr.Dr .Magdy Ismael Ahmed
Routine H&E, special stains are greatly helpful
STAIN SHOWS GOOD FOR
M. trichrome Type I collagen Fibrosis.
Reticulin Type III collagen.Necrosis
(collapse).Van Giesson
stain Collagen type I Fibrosis
Sirus redType I&III collagen
Permanent stain
PAS with diastase
Complex carbohydrate
(Non-glycogen)
B.M , α1- anti-trypsin globules.
Prussian blue (Perl`s stain)
Iron Blue pigment
Orcein stainVictoria blue stain
Copper,elatsin
Chronic cholestasis.
Perls` stain`
Orcein stain
HBV
I. Diagnosis, grading & staging of
II-Investigation of cholestatic liver disease:
Indications/ III
-Chronic Hepatitis (C & B)
-Fatty liver disease
(steatosis /steatohepatitis)
-Auto-immune hepatitis-Haemochromatosis & Wilson’s disease
-Other metabolic liver diseases
-Large duct biliary obstruction
-Primary biliary cirrhosis
-Primary sclerosing cholangitis
-Drug reaction
-Biliary atresia & ductopenia
-Diagnosis of a liver mass
-Evaluation of fever of unknown origin
-Evaluation of post-transplant status
Ultilization of appropriate needle (type ,size..) Careful choice of sampled area:- -Away from the capsule(>0.5 cm,to
avoid septum and focal nodularity) -Right lobe better than left lobe
(larger in size ,covered by little capsule) Appropriate sample (length=1.5cm,wideth1-2
mm 6-8 portal triads ) Appropriate preparation and reading.
Semiquantitative analysis (Ishake &METAVIR)
Morphometric analysis (not clinically useful)
Non-invasive techniques {serological assess –ment (fibro test ,acti test) ,radiological /US measurements (fibroscan)}
Liver biopsy (gold standard)
The two most widely applied scoring
systems in assessment of Chronic
hepatitis C are:
Ishak et al., 1995 (Modified Knodell and
his colleagues)
METAVIR System(A group of French
investigators, 1994 )still most
commonly used system
Grading:- describe the intensity of necro-
inflamm atory activity in chronic hepatitis .its
range (0-18).
Staging :-It measures fibrosis and
architectual alteration . Its range (0-6)
Grading and staging must be regarded as
approxim -ation ,considering the size and
sample quality.
Parameters of grading :
1- Portal inflammation: Score (1- 4).2- Interface hepatitis: Score (1- 4).3- Spotty (Focal) lytic necrosis: Score (1- 4). 4- Confluent necrosis: Score (1- 6). ----------------- 18
0 Absent1 Mild, some or all portal tracts2 Moderate, some or all portal tracts3 Moderate/ marked, all portal tracts4 Marked, all portal tracts
Types of necrosis :- Focal (spotty) lytic necrosis and Apoptosis with liver
cell drop out :- Death and removal of individual hepatocytes within intact parenchyma performed by T-lymphocyte and the residual of cells removed by blood flow or phagocytosis.
Confluent necrosis (simple & zonal) :-death and removal of adjacent group of hepatocyts . It is commonly peri-venular. (zone 3)
Bridging necrosis:- Confluent necrosis connecting two structures (either C-C or P-C or P-P)
Panacinar (multiacinar):-confluent necrosis involve the three zones and destroy the entire acinus.
Interphase hepatitis(Piece meal necrosis ):- Death of hepatocyts at interphase of parenchyma and C.T of portal area ( Interphas hepatitis is preferred than piece meal necrosis due to inflammation > necrosis and due to apoptosis other than necrosis)
0 Absent 1 Mild (focal, few portal tracts) 2 Mild/ moderate (focal , most portal tracts) 3 Moderate (involving <50% of all tract’ circumferences) 4 Severe (involving >50% of all tracts’ circumferences)
Interface hepatitisInterface hepatitis
<50% >50%/ Moderate
0 Absent 1 One focus or less per 10X objective 2 2-4 foci 3 5-10 foci 4 More than 10 foci
0-Absent 1 Focal (away from zone 3) 2 Zone 3 necrosis, in some areas 3 Zone 3 necrosis in most areas 4 Zone 3 + occasional p-c. 5 Zone 3+ multiple p-c. 6 Panacinar or multiacinar necrosis
4 Portal inflammation 4 Interface hepatitis 4 Spotty necrosis 6 Confluent necrosis 18 Maximum Total
(S)
Change Score
-No fibrosis 0
- Some portal (Expanded) ± short fibrous septa 1
-Most portal areas(Expanded) ± short fibrous septa
2
-Most portal areas (Expanded) + occasional (P-P) bridging
3
-Portal areas (expanded) + Marked (P-P) & (P-C) Bridging
4
-Marked bridging (P-P and/or P-C) + occasional nodules ( incomplete cirrhosis or merging into cirrhosis)
5
Probable or definite cirrhosis 6
0 1 2 3 4 5 6
F3
F4
F5
F6
Separately assess the degree of Activity (A) and Fibrosis (F)Stages of fibrosis (F0-F4), similar to Scheuer.F0: No fibrosis.F1: Portal tract fibrosis without septaF2: Portal tract fibrosis with rare septaF3: Numerous septa without cirrhosis.F4: Cirrhosis.
F1F2
F4
F3
Ishak, 1995. activity grade : A ( 0-18)
METAVIR. Activity grade: A ( 0-3 )
Score (1-6 )
Score (7-12)
Score (13-18)
A1
A2
A3
Grade of activity (A0-A3) A0: No histologic necro-inflammatory injury A1: Minimal activity A2: Moderate A3: Marked (Severe) activity
The degree of activity is assessed by integration of both piecemeal necrosis and lobular necrosis as described in a simple algorithm.
Portal lymphoid infiltrate and bridging necrosis are not considered .
Interface hepatitis, with detected apoptotic body
PMN=0LN= oLN= 1LN= 2
LN=0,1LN=2
LN=0,1LN=2
LN=0,1,2
PMN=1
PMN=2
PMN=3
A=0A=1A=2
A=1A=2
A=2
A=3
PMN=piece meal nerosis.0=none,1=mild,2=mderate ,3=severeLN=Lobular necrosis.). 0=none or mild ,1=moderate ,2=severeA=Histological activity .0=None ,1=Mild,2=moderate,3=Severe
MILD ACTIVITY (A1)
+
Periportal necrosis = 1 Lobular necrosis =1
METAVIR - Algorithm
NL = 0 A = 0 NP = 0 NL = 1 A = 1 NL = 2 A = 2 NP = 1 NL = 0,1 A = 1 NL = 2 A = 2 NL = 0,1 A = 2 NP = 2 NL = 2 NP = 3 NL = 0,1,2 A = 3
SEVERE ACTIVITY (A3)
+
Periportal necrosis = 2 Lobular necrosis = 2
P. Bedossa
METAVIR - Algorithm
NL = 0 A = 0 NP = 0 NL = 1 A = 1 NL = 2 A = 2 NP = 1 NL = 0,1 A = 1 NL = 2 A = 2 NL = 0,1 A = 2 NP = 2 NL = 2 NP = 3 NL = 0,1,2 A = 3
1-auto-immune hepatitis-: -Clinical findings
1-Common in females (M:F -1:9) 2-Elevated liver enzymes at disease activity .
3-Presence of polyclonal hyper- gammaglobulinemia and auto-immune Abs (ASMA,ANA,ALVKM.ect)
4-Absence of viral markers-Histological findings: -
1-Extensive interface hepatitis rich in plasma cells 2-Rosetting of hepatocyts
3-Lobular inflammation may or may not be present 4-Intact bile ducts (D.D PBC) 5-The inflammation may lead to portal fibrosis , bridging
& cirrhosis
[.
BD
a-Absence of viral markersb-Presence of PAS +ve DR globules or Hx&E
stained globules in periportal areas, in cases of α 1-anti-trypsin deficiency.(genetic disorder ,discovered in infants and children. In which the synthesized protein fail to migrate from (ER) to Golgi zone and thus accumulates inside ER as hyaline globules (arrows).
c-Or Presence of Mallory hayline bodies ,fatty change ,micronodular cirrhosis and cu in periportal heptocytes in cases of Wilson,s diasese
PAS +ve DR
Mallory bodies
3-Drug induced hepatitis
(Aldomet,inhibix,macrodantin,diclofenac)
a-Absence of viral markers or b-Drug induced auto-antibodies or CU. c-History of taking the drug.
D.D diseases mimic Ch.V.hepatitis .
1- PBC :- a-Markdely elevated Alk.phosphatase & GGT. b->90 % of cases, with high titres of circulating anti- mitochondrial antibodies (AMA) c- Granulomatous destruction of small and medium
sized intrahepatic bile ducts d-Ductular proliferation e-Peripheral cholestasis f-The inflammation may lead to scarring & cirrhosis
A chronic cholestatic liver disease (raised alkaline phosphatase)
In which there is progressive fibro-oblitrative destruction of segments of the extrahepatic and large intrahepatic bile ducts
On endoscopy gives a specific beaded appearance (strictures & dilatations)
There is ulcerative colitis in 70% of patients
Cholestasis
2-Lymphoma &leukemia (dense lymphoplasmacytic infiltrates):-
a-No-true interface hepatitis b-No true apoptosis only
hepatocyte atrophy c-No fibrosis. d-No acidophil bodies. e-Monomorphism ,marked atypia
1.Count the number of portal tracts(6-8)
2. Note portal tract expansion & septa formation (best done with reticulin stain)
3. Examine the portal tracts
4. Assess Interface hepatitis
5. Spotty necrosis6. Confluent necrosis
7. Any steatosis, what type & how much
8. Any iron, and how much
9. Any copper-associated protein?
1-The statement that it is chronic hepatitis and mention the known or suspected cause of the hepatitis
2-The grade of activity (including the name of scoring system itself)
3-The stage of activity (including the name of scoring system itself)
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