Pathology of the Liver
2
Dr. Shaun Walsh
Dept. of Pathology
Ninewells Hospital.
Lecture Plan
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Normal liver structure and injury
Acute liver failure
Cirrhosis
Alcoholic liver disease
Viral hepatitis
Other causes of chronic Hepatitis….
PBC,AIH, PSC
• Storage diseases
• Tumours of the liver
Viral Hepatitis
• May cause acute liver injury or chronic liver injury
• Many agents
• Common and rare causes exist
Hepatitis A
Hepatitis B
Hepatitis C
Hepatitis E
Delta agent
Ebstein-Barr virus
Yellow fever virus
Herpes Simplex virus
Cytomegalovirus
Hepatitis A
• Faecal-oral spread
• Short incubation period
• Sporadic or endemic
• Directly cytopathic
• No carrier state
• Mild illness, usually full recovery
Hepatitis A
Hepatitis B
• Spread by blood, blood products,
sexually, vertically (in utero)
• Long incubation period
• Liver damage is by antiviral immune
response
• Carriers exist
• Outcome is variable
Hepatitis C
• Spread by blood, blood products,
possibly sexually
• Short incubation period
• Often assymptomatic
• Disease waxes and wanes
• Tends to become chronic
Chronic Viral Hepatitis
Dense portal chronic inflammation
Chronic Viral Hepatitis
Portal inflammation
Chronic Viral Hepatitis
Interface Hepatitis (piecemeal necrosis)
Chronic Viral Hepatitis
Lobular inflammation
Arrow shows a councilman body. Small amount of steatosis is present
Chronic Viral Hepatitis
Fibrosis
Chronic Viral Hepatitis
Cirrhosis
Hepatitis B
Outcome
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Fulminant acute infection (Death)
Chronic hepatitis
Cirrhosis
Hepatocellular carcinoma
Assymptomatic (Carrier)
Hepatitis C
Outcome
• Chronic Hepatitis
• Cirrhosis
Lecture Plan
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Normal liver structure and injury
Acute liver failure
Cirrhosis
Alcoholic liver disease
Viral hepatitis
Other causes of chronic Hepatitis….
PBC,AIH, PSC
• Storage diseases
• Tumours of the liver
Chronic Hepatitis
Aetiology: Autoimmune diseases
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Hepatitis B
Hepatitis C
Primary Biliary Cirrhosis
Autoimmune hepatitis
Drug induced hepatitis
Primary Sclerosing Cholangitis
Primary Biliary Cirrhosis
• Rare autoimmune disease, unknown
aetiology
• Associated with autoantibodies to
mitochondria
• Females (90%)
• Indication for biopsy: Stage the disease
• May see granulomas and bile duct loss
Primary Biliary Cirrhosis
Chronic Portal Inflammation
Primary Biliary Cirrhosis
Bile ducts inflamed
Primary Biliary Cirrhosis
Granuloma around duct
Primary Biliary Cirrhosis
Cirrhosis
If untreated bile duct loss leads to cholestasis
liver injury, inflammation, fibrosis and cirrhosis
Autoimmune Hepatitis
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Commoner in females
Associated with other AI diseases
Chronic hepatitis pattern
Numerous plasma cells
Autoantibodies to smooth muscle,
nuclear or LKM, raised IgG
• May have triggers, including some
drugs
Chronic Drug-induced Hepatitis
• Similar features to all other types of
chronic hepatitis
• May trigger an autoimmune hepatitis
• Chronic active process
• Causes are too many to list
Drugs and the liver!
General points
• Innumerable drugs can damage the liver
• May be dose related or idiosyncratic
• Can cause hepatitis, granulomas, fibrosis,
necrosis, failure, cholestasis or cirrhosis
• Can mimic any liver disease
Primary Sclerosing Cholangitis
• Chronic inflammatory process affecting intra
- and extra-hepatic bile ducts
• Leads to periductal fibrosis, duct
destruction, jaundice and fibrosis
• Associated with Ulcerative Colitis
• Males
• Increased risk of malignancy in bile ducts
and colon
Primary Sclerosing Cholangitis
Periductal onion-skinning fibrosis
Lecture Plan
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Normal liver structure and injury
Acute liver failure
Cirrhosis
Alcoholic liver disease
Viral hepatitis
Other causes of chronic Hepatitis….
PBC,AIH, PSC
• Storage diseases
• Tumours of the liver
Storage diseases
• Haemochromatosis
• Wilsons disease
• Alpha-1-antitrypsin deficiency
Iron and the Liver
• Haemochromatosis is excess iron
within the liver
• Primary: Genetic condition, increased
absorption of iron
• Secondary: Iron overload from diet,
transfusions, iron therapy
Primary Haemochromatosis
A iron handling/storage disorder
• Inherited autosomal recessive
condition
• Gene defect v.complex
• Excess absorbtion of iron from
intestine, abnormal iron metabolism
• Worse in homozygotes, men
Primary Haemochromatosis
• Iron deposited in liver, assymptomatic for
years
• Eventually deposited in portal connective
tissue and stimulates fibrosis
• Cirrhosis if not treated
• Predisposes to carcinoma
• Also causes diabetes, cardiac failure and
impotence
Haemochromatosis
Iron accumulates in Hepatocytes
Haemochromatosis
Iron is confirmed by Perls stain
Haemochromatosis
Outcome
• Outcome depends on
genetics, therapy
(venesection) and
cofactors such as
alcohol
• Cirrhosis
• Hepatocellular
carcinoma
If untreated may lead to fibrosis and cirrhosis
Wilson’s Disease
• Inherited autosomal recessive disorder of
copper metabolism
• Copper accumulates in liver and brain
(basal ganglia)
• Kayser-Fleischer rings at corneal limbus
• Low serum caeruloplasmin
• Causes chronic hepatitis and neurological
deterioration
Alpha-1-antitrypsin deficiency
• Inherited autosomal recessive
disorder of production of an enzyme
inhibitor
• Causes empysema and cirrhosis
• Cytoplasmic globules of unsecreted
globules of protein in liver cells
Alpha-1-antitrypsin deficiency
Lecture Plan
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Normal liver structure and injury
Acute liver failure
Cirrhosis
Alcoholic liver disease
Viral hepatitis
Other causes of chronic Hepatitis….
PBC,AIH, PSC
• Storage diseases
• Tumours of the liver
Tumours of Liver
• Primary (rare)
- Hepatocellular adenoma
- Hepatocellular carcinoma (Hepatoma)
• Secondary (common)
- Multiple
- Metastases from colon, pancreas,
stomach
breast, lung, others….
Hepatocellular Adenoma
• Benign
• Females
• May become large…can rupture or
bleed
• Most remain assymptomatic
Hepatocellular Adenoma
Hepatocellular Adenoma
Hepatocellular Carcinoma
• Rare in Europe
• Associated with HBV, HCV and Cirrhosis
• Usually presents as a mass, pain, obstruction
• Usually advanced unless discovered
incidentally
• Poor prognosis
Hepatocellular Carcinoma
Hepatocellular Carcinoma
Multifocal (rare)
Hepatocellular Carcinoma
Histopathological types
Cholangio-
Hepatocytic
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B.
Metastatic Carcinoma
Usually incurable disease unless single solitary metastasis
Lecture Plan
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Normal liver structure and injury
Acute liver failure
Cirrhosis
Alcoholic liver disease
Viral hepatitis
Other causes of chronic Hepatitis….
PBC,AIH, PSC
• Storage diseases
• Tumours of the liver