Liver Pathology Made Easy - PowerPoint Presentation

Slide1

Liver Pathology Made Easy and Understandable II – Patterns of Inflammation

Dr Ian ChandlerFebruary 2013

With acknowledgements to Prof S

Hubscher

, BirminghamSlide2

Patterns of Inflammation in the LiverPortal 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 lobularSlide3

Normal Liver

Liver Zones

Zone 1

(periportal)

Zone 2

(mid-

zonal

)

Zone 3

(

perivenular

or

centrilobular

)Slide4

Portal Inflammation – Histological Assessment

Aetiology Known (e.g. hepatitis B & C)

Assess disease severity

inflammation grade – interface hepatitis

fibrosis stage

Identify co-existent disease (e.g. NAFLD)

Aetiology Suspected (e.g. autoimmune hepatitis)Identify features supporting suspected diagnosis (absence of features suggesting an alternative diagnosis)

Aetiology Uncertain/UnknownPattern & composition of inflammatory infiltrate (and other associated features) may provide diagnostic cluesSlide5

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 NASHSlide6

Hepatitis CSlide7

Autoimmune HepatitisSlide8

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: d

rug reaction, biliary obstruction, PBC & PSC, parasitic infestation, acute allograft rejection Slide9

Granuloma in HCVSlide10

Eosinophils in acute rejectionSlide11

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 activitySlide12

Interface hepatitis in AIHSlide13

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”)Slide14

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

Establishing a diagnosisLiver biopsy no longer required in cases with other typical features

Still important in the diagnosis of atypical casese.g. AMA-negative PBC, small duct PSC-, IgG4-associated SCDiagnostic duct lesions only present in liver biopsies from:

30-50% of PBC cases (

Wiesner 1985, Drebber 2008)12% of PSC cases (Wiesner 1985) Slide15

PBCSlide16

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 immunosuppressionNormalisation of ALT levelsLess severe fibrosis progression

Similar

comments apply to PSCSlide17

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 Slide18

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)Slide19

Acute (and chronic) Hepatitis

Histological Findings in Liver Parenchyma

Inflammatory Infiltration -

mainly lymphocytes ( T cells >> B cells) - plasma cells (

esp

in AIH) - neutrophils (

esp

in alcoholic hepatitis) - eosinophils (

esp

in drug reactions)

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)Slide20

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)Slide21

Acidophil bodySlide22

Multiacinar

Necrosis

Normal vascular

relationhips

Prominent

ductular

reaction (resembling

biliary

obstruction)Slide23

Could this be cirrhotic?Slide24

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)Slide25
Slide26
Slide27
Slide28

Acute Hepatitis - Common Causes

Viral

Hepatitis viruses – A,B,C,D, E

Other viruses – e.g. CMV, EBV

Drugs

Autoimmune

Unknown

Seronegative

hepatitis (“non-A, non-B, non-C hepatitis”)Slide29

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

Acute Hepatitis -

Aetiological

Considerations

Aetiology

Suggestive Histological features

Drugs

Disproportionately severe necrosis/unusually prominent

cholestasis

(relatively

little inflammation – lobular and/or portal)EosinophilsGranulomas Autoimmune

hepatitisPlasma cell rich infiltrate (also seen in hepatitis A)Prominent periportal inflammation (interface hepatitis)Prominent centrilobular inflammation (“central

perivenulitis”)Lymphoid aggregatesSlide30

Role of Liver Biopsy in Fatty Liver Disease

Establishing a morphological diagnosis

Distinction between

steatosis

and

steatohepatitis

Recognition of portal tract changesAetiological pointersAFLD versus NAFLD

cases with a dual pathology (e.g. HCV and NAFLD)Biopsy may help to identify the main cause of liver injury

Assessing disease severity grading of fat, ballooning, inflammation

staging of fibrosisSlide31

Alcoholic steatohepatitis with cirrhosisSlide32

HCV with fat ?causeSlide33