Pathology of Liver

• Liver cell Necrosis

  Classification of necrosis: Non-Zonal (Single cell, Focal, Bridging, Submassive, Massive) and Zonal (Periportal, Mid-zonal, Central)
• Zonal necrosis

  1. All acini involved in similar way

  2. Perfusion linked

  3. Seen in prolonged severe shock/severe left-sided failure

  4. Hepatocytes in central region undergo ischaemic necrosis (zone most distant from blood supply, zone 3)
• Acute liver injury

  • May present with acute onset of jaundice/clinical symptoms
  • Causes include viruses, alcohol, drugs, bile duct obstruction
  • Possible outcomes include complete recovery, chronic liver disease, or death from liver failure
• Viral hepatitis

  • Common cause of acute liver injury
  • Hepatitis viruses A, B, C and E, and delta agent
  • Other viruses causing liver damage include Epstein-Barr virus, yellow fever virus, herpes simplex virus and cytomegalovirus
• Histological features of viral/other acute hepatitis

  • Apoptotic necrosis (resulting in Councilman or acidophil bodies)
  • Necrosis varies: single cell, focal, bridging, sub- or massive necrosis
  • Portal tract inflammation and/or lobular inflammation
  • Cholestasis
  • Regeneration - rosettes
• Chronic hepatitis


  Clinical or biopsy evidence of hepatitis lasting more than 6 months
• Causes of chronic hepatitis

  • Hepatitis viruses, principally HBV and HCV
  • Alcohol
  • Drugs
  • Autoimmune hepatitis
• Histological classification of chronic hepatitis

  Assesses the aetiological type of hepatitis, the grade of severity of the liver cell damage and inflammation, and the stage of the degree of architectural disturbance/cirrhosis
• Cirrhosis

  • Complication of persistent liver disease
  • Diffuse and irreversible process
  • Characterised by fibrosis and nodular regeneration
  • Classified morphologically and aetiologically
  • Causes include HBV, HCV, alcohol, haemochromatosis and many others
  • Complications are liver failure, portal hypertension and liver cell carcinoma
• Morphological classification of cirrhosis

  • Micronodular - nodules up to 3mm diameter
  • Macronodular - nodules greater than 3mm diameter
  • Mixed - intermediate between micronodular and macronodular
• Aetiological classification of cirrhosis

  • Viral hepatitis (HBV and HCV)
  • Alcohol
  • Haemochromatosis
  • Autoimmune liver disease (autoimmune hepatitis and primary biliary cirrhosis)
  • Recurrent biliary obstruction (e.g. gallstones)
  • Rare e.g. Wilson's disease
• Hepatitis A

  • May be asymptomatic (children) if little necrosis
  • Increasing viral load leads to necrosis, symptoms/signs (ill, jaundice, abnormal LFT)
  • Occasionally sub-or massive necrosis leading to death
  • Does not lead to chronic hepatitis therefore cirrhosis is not seen as a complication
• Hepatitis B

  • Common in Southern-Africa
  • Acute with recovery (elimination of virus, acquiring immunity) or chronic
  • Chronic infection typically results in histological picture of interface hepatitis with piece-meal necrosis (single cell peri-portal necrosis)
  • May also lead to bridging/sub-massive necrosis if extensive necrosis
  • Regeneration typically leads to macro-nodular cirrhosis
  • Risk for carcinoma
• Hepatitis C


  • Increasingly common cause of chronic hepatitis
  • May have few symptoms/signs
  • Often dense chronic inflammatory infiltrates in portal tracts, bile duct damage
  • Background of fatty change
  • Cirrhosis
  • Carcinoma risk
• Alcoholic liver injury

  Spectrum includes fatty change (reversible), acute hepatitis with Mallory's hyaline (reversible), focal liver cell necrosis, acute inflammation, architectural damage ranging from fibrosis to cirrhosis (irreversible)
• Alcoholic liver disease

  • Fatty change, inflammation and Mallory hyalin
• Liver biopsy of micronodular cirrhosis

  • Special stain for connective tissue
• Drug-induced liver injury

  • At least 10% of drug reactions involve the liver
  • May be cholestatic or hepatocellular
  • Pathogenesis may be dose-related (predictable) or idiosyncratic (unpredictable)
• Non-alcoholic steatohepatitis (NASH)


  • More recently described entity initially reported in diabetic patients
  • Marked fatty change with variable inflammation
  • May less commonly progress to cirrhosis
• Iron overload and the liver

  • Excessive accumulation of iron, as haemosiderin, in the liver causes it to appear dark brown
  • Haemosiderosis: excess iron with normal architecture
  • Haemochromatosis: excess iron with consequent cirrhosis
  • Primary haemochromatosis (congenital): excess iron absorption, deposited in liver (cirrhosis) and endocrine glands/skin
  • Secondary haemochromatosis (acquired): excess dietary iron or parenteral administration (e.g. multiple blood transfusions)
• Special stain showing iron deposition

  • Blue
• Wilson's disease


  • Inherited disorder of copper metabolism
  • Low serum caeruloplasmin (low levels of copper binding protein)
  • Copper accumulates in liver and brain
  • Cirrhosis
  • Kayser-Fleischer rings at corneal limbus
• Alpha-1-Antitrypsin deficiency

  • Congenital defect of synthesis
  • Accumulates in liver
  • Hyaline globular inclusions in liver cells
  • Risk of emphysema and cirrhosis
• Autoimmune liver disease


  Autoimmune hepatitis and primary biliary cirrhosis are considered to have an autoimmune basis
• Autoimmune hepatitis

  • Females > males
  • Liver biopsy shows chronic hepatitis, often with plasma cells and liver cell rosettes
  • Anti-smooth muscle, anti-nuclear or anti-LKM antibodies, raised IgG and transaminases
• Primary biliary cirrhosis

  • Females > males
  • Liver biopsy shows bile duct destruction, granulomas, ductular proliferation, fibrosis, and even cirrhosis
• Secondary haemochromatosis


  Excess dietary iron or parenteral administration (e.g. multiple blood transfusions)
• Deposition of iron

  • Liver (cirrhosis)
  • Endocrine glands
  • Skin (e.g. 'bronze diabetes')
• Special stain showing iron deposition (blue)
• Haemochromatosis with cirrhosis
• Wilson's disease


  Inherited disorder of copper metabolism
• Low serum caeruloplasmin


  Low levels of copper binding protein
• Copper accumulates in

  Liver and brain
• Kayser-Fleischer rings


  At corneal limbus
• Alpha-1-antitrypsin deficiency

  Congenital defect of synthesis
• Accumulates in liver

  Hyaline globular inclusions in liver cells
• Risk of

  Emphysema and cirrhosis
• There are two chronic liver diseases that are considered to have an autoimmune basis:
• Autoimmune hepatitis

  • Females > males
  • Liver biopsy shows chronic hepatitis, often with plasma cells and liver cell rosettes
  • Anti-smooth muscle, anti-nuclear or anti-LKM antibodies, raised IgG and transaminases
• Autoimmune hepatitis with cirrhosis