Cirrhosis

Question 1

Definition of cirrhosis

Answer 1

• end stage of chronic liver disease
• defined by 3 main morphologic characteristics
  1. Diffuse fibrosis, bridging fibrous septa
  2. Nodule formation
  3. Architectural disruption - destruction of liver lobule - fibrosis joining central & portal vein - fibrous septa containing sinusoids - converted to venules - act as shunts

Question 2

Causes of cirrhosis (4)

Answer 2

1. Alcoholic Liver Disease
2. Chronic hepatitis
   - viral hepatitis (HBV, HCV)
   - autoimmune
   - drug induced
3. Metabolic liver disease
   - hemochromatosis
   - Wilson’s disease
   - α1-antitrypsin deficiency
   - non-alcoholic steatohepatitis
4. Biliary obstruction
   - primary biliary cirrhosis
   - large duct obstruction

Question 3

Pathogenesis of cirrhosis

Answer 3

1. Progressive fibrosis - at portal tracts, central veins, space of Disse
2. Hepatic stellate cells/Ito cells (in space of Disse) - under stress - transform into myofibroblasts - lay down collagen fibres - fibrosis
   - fibrous septal tracts impair solute exchange b/w hepatocytes & plasma 3. Capillarisation of hepatic sinusoids - new vascular channels - shunts blood away from liver parenchyma
3. Hepatocyte death & regeneration within confines of bridging fibrous septa - forms parenchymal nodules w/o normal lobular architecture

Question 4

Gross morphology of liver cirrhosis

Answer 4

• Size - early stage - enlarged due to fat infiltration, end stage - shrunken due to loss of hepatocytes, fibrosis
• Colour - varies depending on cause - yellow (fatty change, alcohol), grey (viral hep), green (jaundice), brown (hemochromatosis)
• Consistency - more firm, turgid (fibrosis)
• Surface - nodular, irregular, granular

Question 5

Microscopy of liver cirrhosis

Answer 5

1. bridging fibrous septa
2. parenchymal nodules comprising hepatocytes (micronodular 3mm - viral hep, irregular nodules - biliary)
3. inflammatory infiltrate
4. ductular proliferation within fibrous septa
5. cholestasis
6. piecemeal necrosis/interface hepatitis

Question 6

Features of alcoholic liver disease

Answer 6

1. Micronodular
2. Fatty change
3. Mallory bodies - reticular eosinophilic depositions in hepatocytes

Question 7

Features of non-alcoholic fatty liver disease

Answer 7

• metabolic syndrome involving insulin resistance & hepatocellular oxidative injury
  1. Fatty change
  2. Mallory bodies
  3. Focal necrosis w neutrophilic reaction

Question 8

Features of cirrhosis associated with viral hepatitis

Answer 8

1. Macronodular

2. Groundglass hepatocytes - due to intracellular accumulation of HBsAg

Question 9

Features of hemochromatosis

Answer 9

• hereditary, results in excessive iron absorption from the intestine - cirrhosis, diabetes, browning of skin
• pigment cirrhosis - hemosiderin (Perl’s stain, Prussian blue) in hepatocytes, Kupffer cells, bile duct epithelium & fibrous stroma

Question 10

Features of Wilson’s disease

Answer 10

• hereditary, results in impaired copper excretion into bile & failure to incorporate copper into ceruloplasmin - increased copper in tissues
• Mallory bodies
• aggregation of copper within lysosomes principally in the periphery of the nodule (rhodamine stain)

Question 11

Features of α1-antitrypsin deficiency

Answer 11

• AR disorder of protein folding
• defect in migration of protein from ER to GA - ER stress - apoptosis
• PAS positive diastase resistant α1-antitrypsin globules (red, eosinophilic) in cytoplasm of hepatocytes

Question 12

Features of primary biliary cirrhosis

Answer 12

• autoimmune, characterised by non suppurative, inflammatory destruction of intrahepatic bile ducts
• periportal fibrosis
• mononuclear cellular infiltrate
• lymphoid follicles
• granuloma formation
• non-suppurative destructive cholangitis

Question 13

Features of secondary biliary cirrhosis

Answer 13

• periportal fibrosis
• prominent cholestasis - bile lakes
• bile duct proliferation
• neutrophilic infiltrate
• intraduct neutrophils