Transcript Chronic Hepatitis - Patologos de Puerto Rico

Pathology of Chronic Viral Hepatitis:
Nomenclature
Grade & Stage
Carmen Gonzalez Keelan MD
FCAP FASCP
Consultant, UPR School of Medicine
Chronic hepatitis: term used when
there is clinical evidence of
chronicity (hepatic necrosis
33%
33%& 33%
inflammation lasting>6 months)
Do you agree?
in
Ab
st
a
No
Ye
s
1. Yes
2. No
3. Abstain
Causes of chronic hepatitis
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VHB
VHC
Autoimmune
A1AT
Wilson
Drug hepatotoxicity
Which virus is responsible for
40% of acute hepatitis in USA?
25%
HD
V
25%
HC
V
25%
HB
V
HAV
HBV
HCV
HDV
HA
V
1.
2.
3.
4.
25%
Chronic Liver disease
72/100,000
8th cause of death, between diabetes
& suicide
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Viral hepatitis C: 57%
Alcohol: 24%
NAFLD: 9%
Viral hepatitis B: 4%
44,000 (1.9%) deaths
HCV
• Chronic infection occurs in 85% of patients
• Cirrhosis develops in 20-40% *
• Chronic hepatitis C accounts for 30% of
liver transplants in USA
• Annual risk of hepatocellular cancer:
1-4% (genotype 1b)
Occult HCV infection
• Persistent LFT elevation with negative
HCV serology
• Positive HCV serology with normal LFT*
Role of the biopsy in
Chronic liver diseases
• Confirm diagnosis
• Assess prognosis
• Guide treatment
• Goodman, Z J Hepatol 47 598-607, 2007
Biopsy adequacy: 2 cm
• We must educate clinicians to supply
adequate samples by obtaining long core or
repeating passes
• Right lobe
• Tru cutt or Bard needles
• Thin needles are unsuitable for staging
Chronic Hepatitis
Elements of the Pathologic
Report
• Etiology
• Grade
• Stage
• Chronic Hepatitis: An Update on Terminology &
Reporting Batts & Ludwig AJSP 19 (2): 1409-17, 1995
Grading & Staging Systems in
Chronic liver diseases
• Stage: degree of scarring
• Grade: severity of disease process
• Try to predict outcome
• Goodman, Z J Hepatol 47 598-607, 2007
Scoring Systems
• Complex: statistical analysis
– Knodell 1981 (0-22) includes fibrosis score
– Ishak modified HAI (0-18) with separate
fibrosis score (1-6) 1995
• Evaluation of individual patients:
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–
–
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Scheuer 1991
IASL 1994
Batts & Ludwig 1995
Metavir 1996
Grade of Inflammation
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Portal inflammation: dense mononuclear
Interface activity
Lobular inflammation
Parenchymal injury: ballooning, apoptosis
& bridging necrosis
Portal inflammation
Lymphocytes, PC
• T lymphocytes plasma cells & eosinophils
• Lymphoid follicles with GC HCV
Interface Hepatitis:
Mononuclears with hepatocyte engulfment in
limiting plate
• Piecemeal / periportal necrosis
• Ballooning degeneration &
Apoptosis of hepatocytes
• Tumor necrosis factor related apoptosis
inducing ligand receptors (TRAIL)
Interface hepatitis:
Mild: occasional
Moderate <50%
Marked > 50:%
Lobular Necro-inflammatory
activity
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Variable & spotty necrosis
Apoptosis, ballooning degeneration
Zone 3 cholestasis
Regenerative 2ble liver cell plates & rosettes
Parenchymal injury
• Mild
• Moderate >5 foci /10 HPF
• Marked numerous necroinflammatory foci
(bridging necrosis)
Batts-Ludwig: Grade 0-4
Bridging or confluent Necrosis
Which features of chronic viral
hepatitis are seen?
• Interface hepatitis
• fatty change,
• ballooning
degeneration
• predominantly portal
inflammation
• Bridging necrosis
• Cirrhosis
sis
17%
Ci
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o
...
17%
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an
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...
17%
Br
id
do
m
in
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e
lo
on
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d
eg
ge
,
ch
an
17%
...
17%
ba
l
fa
tty
In
te
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ce
he
pa
.. .
17%
This biopsy’s interface hepatitis
is best graded as Scheuer’s
4
25%
Gr
ad
e
3
25%
Gr
ad
e
2
25%
Gr
ad
e
Grade 1
Grade 2
Grade 3
Grade 4
Gr
ad
e
1.
2.
3.
4.
1
25%
Comparison of simple scoring
systems for grading
chronic hepatitis
IASL
Batts-Ludwig
Minimal activity
Grade 1
Mild activity
Grade 2
Moderate activity
Grade 3
Marked activity
Grade 4
Marked & bridging necrosis
Grade 4
Metavir
A1
A1
A2
A3
A3
Stage: Degree of Fibrosis
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Fibrosis: periportal, may be perivenular
Early fibrosis
Incomplete septae
Complete portoportal septae
Cirrhotic stage
Fibrosis
• Rounded
enlargement of portal
tracts / stellate
periportal scars with
bridging
• Progression to
cirrhosis
Fibrosis: Does sample size affect
staging accuracy?
33%
33%
33%
in
Ab
st
a
No
Ye
s
1. Yes
2. No
3. Abstain
Batts-Ludwig: Stage 0-4
Bridging
cirrhosis
Portal fibrosis
normal
Comparison of Simple systems
for Scoring Fibrosis
Definition
No fibrosis
Portal
expansion
Few septae
Many septae
Cirrhosis
IASL
No fibrosis
Mild
Moderate
Severe
Cirrhosis
Batts-Ludwig Metavir
Stage 0
F0
Stage 1
F1
Stage 2
Stage 3
Stage 4
F2
F3
F4
Kappa Statistic
Measure of observer variability
• 0 (chance)  1 (perfect)
• Fibrosis:
.5-.9 (fair excellent)
• Inflammation:
.2-.6 (slight-moderate)
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Cardiac auscultation
Varices endoscopy
Mammograms
Breast cancer grading
.19
.38
.47
.43-.74
Consistency & accuracy
• Subspecialty expertise
• > 10 years in academic center
• Improved specimen interpretation despite
small biopsy size
• Rousselet, et al Hepatology 2005 41: 257-64
Nomenclature & Scoring
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Chronic Hepatitis
Severity of necroinflammatory activity (grade)
Extent of Fibrosis (Stage)
Etiology
System used in scoring
“Chronic viral hepatitis C/B/D with
mild/moderate/marked activity in early fibrosis
/incomplete/ portoportal septae/cirrhotic stage”
Additional features to be
routinely assessed
• Fat: present in 50% VHC biopsies,
genotype 3, NAFLD
• Hemosiderosis
• Neoplasia: Small cell dysplasis
• HIV
Needle biopsies of a 42 y/o ♀ with chronic ↑AST: 240 &
ALT: 300
Which Metavir grade & stage is most appropriate?
F?
25%
A2
F3
25%
A3
F2
25%
A2
A1 F1
A2 F2
A3 F3
A2 F?
A1
1.
2.
3.
4.
F1
25%
Is this bridging necrosis?
50%
50%
No
Ye
s
1. Yes
2. No
Differential Diagnosis
• Acute hepatitis
• Other Chronic hepatitis:
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–
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–
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Autoimmune
PSC
PBC
Metabolic disorders: Wilson, Heomchromatosis
Drug reactions
Acute vs Chronic Hepatitis
clinical hx
Lobular inflammation
Busy parenchyma
Periportal inflammation
Fibrosis
Autoimmune hepatitis
Serology
Duct proliferation in response
to hepatocyte loss. This
ductular reaction is fibrogenic
Interface hepatitis with ↑ PC
PSC
PBC: non suppurative cholangitis
Metabolic Disorders
• Wilson disease: copper stain
• Hemochromatosis: Iron stain
• A1AT: Diastase treated PAS
Non Alcoholic Fatty Liver
Disease (NAFLD)
• 70% chronic hepatitis
of unknown cause
• ♀=♂
• Obesity
• Dyslipeidemia
•  insulinemia with
insulin resistance
• Overt type 2 Diabetes
•  AST, ALT, GGT
24%
Drug Reaction
Graft biopsies
Etiology of organ loss
Rejection vs. Recurrence
New disease
Features of chronic viral hepatitis
• HBV
• Ground glass
hepatocytes
• HCV:
• Fatty change
• Portal lymphoid
aggregates
Therapeutical Response
• Whether using Metavir, Ishak or Knodell,
all HAI scores improve when therapy is
truly effective & show statistical differences
when compared to placebo
• Goodman 2007
It does not matter which system
you use!
• Words provide a picture to the clinician &
to the patient so they will have a dynamic
picture of the disease
• Remember to name the system being used
Summary
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Pathology of chronic hepatitis
Role of the biopsy
Nomenclature
Grading & staging systems
Elements of surgical report
Differential Diagnosis
NAFLD Activity Index
Item
Definition
Score
Steatosis
<5%, <33%, <66% >66%
0-3
Lobular
inflammation
None, <2/20X, <4, >4
0-3
Ballooning
None, Few, many
0-2
Fibrosis
Perisinusoidal /periportal
Both
Bridging
Cirrhosis
1A-1C
2
3
4