basic patterns of liver damage what information can a ... · fatty liver disease ... biliary tract...
TRANSCRIPT
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Basic patterns of liver damage –what information can a liver biopsy
provide and what clinical information
does the pathologist need?
Rob Goldin
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Fatty liver disease
• Is there fatty change ?
• Is there a fatty liver hepatitis?
• What is the cause of the fatty liver disease?
Clinical Liver Disease Volume 2, April 2013, Pages 64–67
(http://onlinelibrary.wiley.com/doi/10.1002/cld.172/full)
Clinical Liver Disease Volume 1, September 2012, Pages 108–111
(http://onlinelibrary.wiley.com/doi/10.1002/cld.31/full)
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Types of fatty change:Large droplet
“mesovesicular fatty change”
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Causes of large droplet fatty change
• Obesity and Diabetes Mellitus
• Protein-calorie malnutrition
• TPN
• Drugs and toxins (e.g. alcohol, corticosteroids)
• Metabolic disorders ( e.g. Wilson’s Disease)
• Infections ( e.g. hepatitis C)
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Types of fatty change:Small droplet
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Causes of small droplet fatty change
• Alcohol
• Fatty liver of pregnancy
• Drugs (e.g. nucleoside analogues)
• Toxins (e.g. Jamaican vomiting disease)
• Inborn errors of metabolism (e.g. urea cycle disorders).
• Reye’s syndrome
• Infections (e.g. Hepatitis A)
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Fatty liver disease: More than just fat
• Is there fibrosis?
• Is there a fatty liver hepatitis?
Ballooning and inflammation
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(B) Normal hepatocytes,
ballooning,
grade 0. Cytoplasm is pink and
granular and liver cells have
sharp angles.
(C) Ballooning, grade 1.
Hepatocytes have rounded
contours with clear reticular
cytoplasm. Size is quite similar
to that of normal hepatocytes.
(D) Ballooning, grade 2.
Cells are rounded with clear
cytoplasm and twice as large as
normal hepatocytes.
Recognising ballooning
Hepatology Volume 56, November 2012 Pages 1751–1759
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Nuclear vacuolation
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Causes of nuclear vacuolation
• Physiological
• Insulin resistance
• Wilson’s disease
• Glycogen storage disease
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Gastroenterology, Volume 146,
Issue 5, 2014, 1231 - 1239
A Histologic Scoring System for
Prognosis of Patients With
Alcoholic Hepatitis
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Histologic features independently associated with 90-day survival included in the Histologic AHHS. ( A – C ) Degree of fibrosis
(Masson trichrome staining): portal fibrosis, expansive areas of liver fibrosis, and cirrhosis, respectively. H&E s...
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Histologic features independently associated with 90-day survival included in the Histologic AHHS. ( A ) Hepatocellular and
canalicular bilirubinostasis ( arrow ). ( B ) Ductular bilirubinostasis ( arrow ). ( C ) Megamitochondria ( arrows ). ( D and E) Mild and
severe PMN infiltration, respectively (arrow). H&E stain.
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Gastroenterology, Volume 146, Issue 5, 2014, 1231 - 1239
Points
Stage of fibrosis
No fibrosis or portal fibrosis 0
Expansive fibrosis 0
Bridging fibrosis or cirrhosis +3
Bilirubinostasis
No 0
Hepatocellular only 0
Canalicular or ductular +1
Canalicular or ductular plus hepatocellular +2
PMN infiltration
No/Mild +2
Severe 0
Megamitochondria
No megamitochondria +2
Megamitochondria 0
The AHHS categories are as follows: mild, 0–3; intermediate, 4–5; severe, 6–9.
AHHS for Prognostic Stratification of AH
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Chronic viral hepatitis
• Assess disease severity:
Grade (necro-inflammation)
Stage (fibrosis)
? Score (using modified Histological Activity Index / METAVIR)
• Assess disease progression or response to treatment
Modern Pathology 2007; 20: S3
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Chronic viral hepatitis
• Hepatitis related changes:
HBV: Ground glass cells
HCV: Lymphoid follicles, hepatitic bile duct damage, fatty change
HDV: Increased lobular activity
• Large cell changeClinical Liver Disease Volume 1, April 2012 , Pages 32–35
(http://onlinelibrary.wiley.com/doi/10.1002/cld.30/full)
Clinical Liver Disease Volume 2, February 2013, Pages 49–51
(http://onlinelibrary.wiley.com/doi/10.1002/cld.139/full)
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HBV: Ground glass hepatocytes
Orcein
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HCV: Lymphoid aggregate/follicle
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HCV: Hepatitic bile duct damage
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HCV genotype 3: Fatty change
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HDV
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Something else going on
• Drug reaction
• Another virus
• Fatty liver disease
fatty liver hepatitis in 5% of liver biopsies of patients with chronic liver disease
Mod Pathol 2003; 16: 49
• Iron overload
In patients with HCV:
stainable iron in 16%,
grade 2 and 3 (out of 4) iron in 7%.
J Gastroenterol Hepatol 2005; 20: 243
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Large cell change (or is it dysplasia?)
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Iron overload
• What is the pattern if iron overload?
• Grade the degree of iron overload
• Assess fibrosis
• ? Send tissue for biochemical iron measurement
Mod Pathol 2007; 20: S31–S39.
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What is the pattern of iron overload?
• Parenchymal • Macrophage
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Patterns of iron overload
• Parenchymal overload
– gut derived iron.
• Macrophage iron
– transfusion derived iron
• Mixed
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Mixed pattern of iron overload:Sickle cell anaemia Ferroportin deficiency
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Autoimmune hepatitis
• Help in making the diagnosis
• Help in assessing the response to treatment
Clinical Liver Disease Volume 3, February 2014, Pages 38–41
(http://onlinelibrary.wiley.com/doi/10.1002/cld.321/full)
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Simplified histological criteria for the diagnosis of AIH
• “Typical”
1. Interface hepatitis
2. lymphocytic / lympho-plasmacytic infiltrates in portal tracts and extending into the lobule
3. rosetting of liver cells
• “Compatible" a chronic hepatitis with lymphocytic infiltration without all the above features
• “Atypical" for AIH when showing signs of another diagnosis.
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Autoimmune Hepatitis
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The Overlap Syndromes of Autoimmune Hepatitis
Clinical Liver Disease Volume 3, January 2014, Pages 2–5
(http://onlinelibrary.wiley.com/doi/10.1002/cld.294/full)
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Drug reaction
• “Any kind of liver disease can be caused by a drug”
• Histological features suggesting a drug reaction:
Eosinophils, plasma cells, granulomas, sharply demarcated necrosis, cholestatic hepatitis
Clinical Liver Disease Volume 4, Issue 1, July 2014, Pages 12–16
(http://onlinelibrary.wiley.com/doi/10.1002/cld.371/full)
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Injury Patterns of Selected Drugs in Common Use
Drug Pattern of Injury
Paracetamol Zone 3 necrosis (with little additional inflammation)
Amiodarone Steatohepatitis-like, with numerous Mallory-Denk bodies
and fibrosis
Amoxicillin-clavulanate Cholestatic hepatitis (with prominent duct injury)
Anabolic steroids Acute cholestasis to cholestatic hepatitis with little duct
injury
Azithromycin Variable: Hepatitis with or without cholestasis
Diclofenac Zone 3 necrosis with lymphocytic inflammation
Isoniazid Acute or chronic hepatitis
Methotrexate Steatosis and fibrosis, sometimes steatohepatitis-like
Minocycline Acute or chronic hepatitis
Nitrofurantoin Acute or chronic hepatitis
Oxaliplatin Hepatoportal sclerosis, sinusoidal dilation, nodular
regenerative hyperplasia
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Drug reaction
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Drug reaction
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Drug reaction
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Histological predictors of severity in drug-induced liver disease.
• More severe disease associated with: 1. necrosis2. fibrosis stage3. microvesicular steatosis4. cholangiolar cholestasis 5. bile duct damage
• Milder disease associated with: 1. granulomas2. increased eosinophils
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http://livertox.nih.gov/
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Biliary tract disease
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Biliary tract disease: Orcein stain
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Biliary tract disease: CK7
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Causes of Disappearing Bile Ducts
• PBC* (and its variants)
• PSC (and its variants)
• Drugs and Toxins
• Chronic transplant rejection
• Graft Vs. Host
• Hodgkin’s Disease, Histiocytosis X
• Sarcoid
• Paucity of interlobular bile ducts
• HIV
• Idiopathic
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Primary Biliary Cholangitits
= the name for Primary Biliary Cirrhosis
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Vascular Disease:Non-cirrhotic portal hypertension
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Vascular Disease:Non-cirrhotic portal hypertension
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Causes of Nodular Regenerative Hyperplasia
• Connective tissue disorders
• Myeloproliferative disorders
• Chronic vascular congestion
• Drugs e.g. steroids, anticancer drugs, anticonvulsants, immunosuppressive agents
Clinical Liver Disease, Volume 6, October 2015, Pages 103–106 (http://onlinelibrary.wiley.com/doi/10.1002/cld.505/full)
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Discrepancy rates in liver biopsy reporting
• fibrosis staging
• recognising and interpreting bile duct disorders
• misdiagnoses of autoimmune hepatitis
J Clin Pathol 2014;67:825-827
Histopathology. 2016 Jan 30. doi: 10.1111/his.12940
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What clinical information does the pathologist need?
• A decent clinical history!
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Clinical information
• Look at the biopsy and write the description without knowing any clinical information
• Only write the conclusion when you have the information
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Example of not very useful clinical information
• “Liver biopsy”
• “Abnormal LFTs”
• “Complex medical history”
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Recent request form
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http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2046-2484