Liver Pathology Made Easy and Understandable II – Patterns

download report

Transcript Liver Pathology Made Easy and Understandable II – Patterns

Liver Pathology Made Easy
and Understandable II –
Patterns of Inflammation
Dr Ian Chandler
February 2013
With acknowledgements to Prof S Hubscher, Birmingham
Patterns of Inflammation in the Liver
• Portal inflammation
– Most chronic liver diseases (e.g. viral, autoimmune)
– Also seen in acute hepatitis
• Lobular inflammation
– Main pattern in acute hepatitis
– Varying degrees of lobular inflammation also commonly present in
chronic viral and autoimmune hepatitis
– Predominant pattern in some chronic liver diseases (e.g. fatty liver
disease)
• Mixed portal and lobular
Normal Liver
Liver Zones
Zone 1
(periportal)
Zone 2
(mid-zonal)
Zone 3
(perivenular or centrilobular)
Portal Inflammation – Histological Assessment
1.
Aetiology Known (e.g. hepatitis B & C)
•
Assess disease severity
•
•
•
2.
inflammation grade – interface hepatitis
fibrosis stage
Identify co-existent disease (e.g. NAFLD)
Aetiology Suspected (e.g. autoimmune hepatitis)
•
3.
Identify features supporting suspected diagnosis
(absence of features suggesting an alternative diagnosis)
Aetiology Uncertain/Unknown
•
Pattern & composition of inflammatory infiltrate (and other
associated features) may provide diagnostic clues
Composition of Inflammatory Cells
in Portal Tracts
• In most conditions, most lymphocytes in portal tracts
are T cells
• B cell rich lymphoid aggregates will be found in HCV
infection and also other conditions such as PBC and
AIH
• Plasma cells are characteristic of AIH, and also
PBC/PSC. They are less common in HCV and NASH
Hepatitis C
Autoimmune Hepatitis
Composition of Inflammatory Cells
in Portal Tracts
• Granulomas are common in sarcoid and PBC, but can
be found in PSC, HCV and drug reactions
• Portal tract neutrophils are mostly associated with a
ductular reaction, in acute biliary obstruction,
chronic biliary disease, and also acute hepatitis
• Eosinophils: drug reaction, biliary obstruction, PBC &
PSC, parasitic infestation, acute allograft rejection
Granuloma in HCV
Eosinophils in acute rejection
Interface Hepatitis (“piecemeal necrosis”)
•
•
Inflammation at the interface between connective tissue (portal tract, fibrous
septa) and the liver parenchyma
Severity classified according to :
– extent around individual portal tracts/septa (focal vs diffuse)
– proportion of portal tracts involved (e.g.<50% vs > 50%)
Hepatitis C
Chronic hepatitis with mild activity
Autoimmune Hepatitis
Chronic hepatitis with severe activity
Interface hepatitis in AIH
Interface Hepatitis (“piecemeal necrosis”)
Periportal hepatocyte ballooning
(Autoimmune Hepatitis)
Periportal fibrosis (HVG)
Severity of interface hepatitis:
• Predicts subsequent development of fibrosis/cirrhosis (HCV, AIH, PBC)
• Guides therapeutic decisions (AIH, ?PBC/PSC – “overlap syndromes”)
PBC & PSC – Changing Role of Liver Biopsy
EASL Clinical Practice Guidelines – J Hepatol 2009; 51: 237-267
AASLD Practice Guidelines – Lindor. Hepatology 2009; 50: 291-308
1.
Establishing a diagnosis
– Liver biopsy no longer required in cases with other typical features
– Still important in the diagnosis of atypical cases
• e.g. AMA-negative PBC, small duct PSC-, IgG4-associated SC
– Diagnostic duct lesions only present in liver biopsies from:
•
•
30-50% of PBC cases (Wiesner 1985, Drebber 2008)
12% of PSC cases (Wiesner 1985)
PBC
Primary Biliary Cirrhosis
Significance of Inflammatory Activity
Severity of inflammatory activity (periportal and lobular)
• Predictive for subsequent progession to fibrosis /cirrhosis & liver failure
• Moderate or severe interface hepatitis also used as a diagnostic criterion for
PBC/AIH “overlap syndrome” (PBC with “hepatitic features”)
10-15% of PBC have additional features supporting a diagnosis of
AIH (biochemical, immunological and histological)
– PBC with “hepatitic features” - worse outcome than “pure” PBC
– May benefit from treatment with immunosuppression
• Normalisation of ALT levels
• Less severe fibrosis progression
Similar comments apply to PSC
Referred Biopsy – Diagnosis Chronic Hepatitis ? Cause
Raised Alk Phos. Autoantibody screen negative.
• Portal inflammation and interface hepatitis
• Biliary features not conspicuous
Orcein Periportal copper-associated protein
Keratin 7 Immunostaining
“intermediate hepatobiliary cells”
Repeat autoantibody testing = AMA-positive
Role of Liver Biopsy in Acute Hepatitis
• Many of the classical morphological studies of acute hepatitis were carried
out before the main causes had been discovered
• Most cases of acute hepatitis now diagnosed on the basis of clinical,
biochemical and serological findings and liver biopsy is rarely indicated
• Liver biopsy may still be carried out in cases where the clinical presentation
is atypical or the cause is uncertain
– Distinguish severe acute hepatitis from decompensated chronic liver disease
– Determine disease severity
– Identify possible aetiological factors (including cases of acute liver injury not
related to hepatitis)
Acute (and chronic) Hepatitis
Histological Findings in Liver Parenchyma
1.
Inflammatory Infiltration
- mainly lymphocytes ( T cells >> B cells)
- plasma cells (esp in AIH)
- neutrophils (esp in alcoholic hepatitis)
- eosinophils (esp in drug reactions)
2.
Hepatocellular Damage
- ballooning
- bile pigment accumulation (bilirubinostasis)
- lobular disarray
- cell death (apoptosis and/or necrosis)
Changes tend to be most marked in perivenular regions (zone 3)
Liver Cell Death in Lobular Hepatitis (acute or chronic)
Pattern of Cell Death
Histological Features
Spotty necrosis
Apoptosis of individual hepatocytes (acidophil bodies)
Confluent necrosis
(zone 3)
Loss of groups of adjacent liver cells
Bridging necrosis
Confluent necrosis linking vascular structures
(central-central or central-portal bridging)
Panacinar necrosis
Loss of hepatocytes in an entire acinus
Multiacinar necrosis
Panacinar necrosis involving several adjacent acini
• Apoptosis > necrosis (in mild forms)
Acidophil body
•
•
Multiacinar Necrosis
Normal vascular relationhips
Prominent ductular reaction (resembling biliary obstruction)
Could this be cirrhotic?
Recent Post-Necrotic Collapse versus Longstanding Fibrosis Use Of Connective Tissue Stains
Stain
Material
Demonstrated
Distribution In
Normal Liver
Changes In Liver Disease
Reticulin
Type III collagen
fibres
Portal tracts,
hepatic sinusoids
Collapse of reticulin
framework in areas of
recent liver cell necrosis.
(few days)
Haematoxylin
Van Gieson
Type I collagen fibres
Portal tracts, walls
of hepatic veins
Increased in hepatic fibrosis
(weeks/months)
Orcein
Elastic fibres
Portal tracts,
walls of hepatic
veins
Found in long-standing
fibrosis/cirrhosis
(months/years)
Acute Hepatitis - Common Causes
1.
Viral
• Hepatitis viruses – A,B,C,D, E
• Other viruses – e.g. CMV, EBV
2.
Drugs
3.
Autoimmune
4.
Unknown
• Seronegative hepatitis (“non-A, non-B, non-C hepatitis”)
Acute Hepatitis - Aetiological Considerations
Liver biopsy rarely identifies a previously unsuspected aetiology
•
Biopsies mostly obtained from people in whom main recognised causes have been
excluded (“seronegative hepatitis”)
•
Biopsy sometimes provides pointers to a previously unsuspected aetiology
Aetiology
Suggestive Histological features
Drugs
•
Disproportionately severe necrosis/unusually prominent cholestasis
(relatively little inflammation – lobular and/or portal)
Autoimmune
hepatitis
•
Eosinophils
•
Granulomas
•
Plasma cell rich infiltrate (also seen in hepatitis A)
•
Prominent periportal inflammation (interface hepatitis)
•
Prominent centrilobular inflammation (“central perivenulitis”)
•
Lymphoid aggregates
Role of Liver Biopsy in Fatty Liver Disease
1.
Establishing a morphological diagnosis
•
Distinction between steatosis and steatohepatitis
•
Recognition of portal tract changes
2.
Aetiological pointers
•
AFLD versus NAFLD
•
cases with a dual pathology (e.g. HCV and NAFLD)
•
3.
Biopsy may help to identify the main cause of liver injury
Assessing disease severity
•
grading of fat, ballooning, inflammation
•
staging of fibrosis
Alcoholic steatohepatitis with cirrhosis
HCV with fat ?cause