127 - Patterns of Liver Injury 1: Pathology of Acute Hepatitis

Question 1

Definition of acute hepatitis

Answer 1

Elevation of serum transaminase enzymes for a period of less than 6 months duration, in a patient with no history of chronic liver disease.

Question 2

Clinical features of acute hepatitis
1
2
3

Answer 2

1) Malaise
2) Nausea
3) Jaundice with hepatitic profile of abnormal liver biochemistry (increased ALT).

Question 3

Clinical signs of acute liver failure
1
2
3

Answer 3

1) Encephalopathy
2) Hypoglycaemia,
3) Coagulopathy

Question 4

Biopsies in hepatitis

Answer 4

Biopsies are not usually done unless the disease is severe,
the cause is uncertain, or there is concern for chronic liver
disease.

Question 5

What can be the cause of clinical acute hepatitis?
1
2
3

Answer 5

1) Acute hepatitis (pathological pattern)
2) Unsuspected chronic liver disease (including alcoholic liver disease)
3) Diffuse malignant infiltration of the liver (rare)

Question 6

What is the pathological definition of acute hepatitis?
1
2

Answer 6

1) A process with the same pathological changes in the liver as acute viral hepatitis
2) Acute hepatitis is a non-specific pattern of liver injury shared by many different causes

Question 7

Causes of acute hepatitis
1
2
3
4
5

Answer 7

1) Acute viral hepatitis (not C - rarely acute)
2) Drug-induced liver injury
3) ‘Natural’ remedies
4) Autoimmune hepatitis
5) Ideopathic (seronegative, acute non-A, non-B hepatitis)

Question 8

Hallmark features of acute hepatitis 
1
2
3
4
5

Answer 8

1) Death of hepatocytes (apoptosis and necrosis).
2) Regeneration of hepatocytes to repopulate areas of hepatocellular death.
3) Absence of fibrosis.
4) Diffuse injury of hepatocytes
5) Resembles viral hepatitis (no neutrophil infiltrate)

Question 9

Acinar zones

Answer 9

Division of liver lobule into three zones between portal vein and hepatic artery.

Question 10

Why is the third acinar zone at particular risk of injury?

Answer 10

Concept of zone 3 as the “vulnerable zone” in a

range of situations (hypoxia, metabolic disorders, toxins, drugs, inflammatory conditions) because has low O2, enzymes.

Question 11

Area of liver most at risk of injury

Answer 11

Acinar zone three

Question 12

Effect on bile canaliculus of inflammation

Answer 12

Closes off canaliculus because heptaocyte swelling impinges on it

Question 13

Mechanism of single cell death in hepatitis

Answer 13

Apoptosis

Question 14

Mechanism of death of a group of adjacent cells in hepatitis

Answer 14

Necrosis

Question 15

Appearance of apoptosis in acute hepatitis

Answer 15

Panlobular apoptosis of hepatocytes

Question 16

Appearance of necrosis in acute hepatitis
1
2
3

Answer 16

1) Appears first around central vein (zone three).
2) When necrosis is more extensive, becomes ‘bridging necrosis’. Bridges between portal vein and portal triad.
3) When very severe, multiacinar/multilobular necrosis (acute liver failure, will need a transplant)

Question 17

How do hepatocytes undergo necrosis in acute hepatitis?

Answer 17

Undergo severe osmotic failure and burst.
You don’t see necrotic cells themselves, but the aftermath (collapse of liver reticulin framework and presence of scavenger macrophages in liver tissue)

Question 18

Does coagulative necrosis arise from acute hepatitis?

Answer 18

No.

Question 19

Gross appearance of a necrotic liver

Answer 19

Spots of pale (where hepatocytes are replicating).

Question 20

Histological appearance of acute hepatitis 
1
2
3
4
5

Answer 20

• Pan -lobular disarray: swollen liver cells, gaps
on liver cell plates.
• Apoptosis.
• Necrosis of variable extent depending on
severity.
• Aggregates of enlarged macrophages.
• Cholestasis.

Question 21

Lobular disarray

Answer 21

Loss of architecture of liver from swelling of hepatocytes.

From water content, hepatocytes become pale pink (on an HE stain)

Question 22

Sequelae of acute hepatitis
1
2
3

Answer 22

• Resolution with restoration of normal structure and function.
• Massive hepatic necrosis – death or liver transplantation.
• Chronic hepatitis – HBV, autoimmune hepatitis and some drugs

Question 23

Most important cause of toxic liver injury in the Western world

Answer 23

Deliberate overdose on paracetamol

Question 24

Paracetamol toxicity
1
2
3

Answer 24

• Intrinsic liver toxin (causes hepatocellular injury in a predictable and dose dependent fashion).
• Liver injury caused by a toxic metabolite (NAPQI) which directly injures hepatocytes and causes depletion of glutathione (a natural anti-oxidant).
• Necrosis occurs preferentially in zone 3 (this is where the enzyme CPY2E1 is located) but can be pan-acinar, multiacinar, or massive.

Question 25

Why does liver necrosis occur preferentially in zone three of the liver acinus?

Answer 25

Because this is where the enzyme that metabolises paracetamol to a toxic metabolite (NAPQl) is preferentially expressed in zone three.

Question 26

Features of paracetamol-induced liver necrosis
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2
3

Answer 26

1) Necrosis of hepatocytes in zone three
2) Necrosis is coagulative
3) Inflammation is minimal

Question 27

Differences between paracetamol-induced liver necrosis and acute hepatitis
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2
3

Answer 27

1) Necrosis is in zone three with paracetamol. Hepatocellular swelling and apoptosis are pan-acinar in acute hepatitis
2) Necrosis is coagulative with paracetamol, lytic with acute hepatitis
3) Minimal inflammation with paracetamol. With acute hepatitis, inflammation present, variable severity, portal and lobular, mixed composition (lymphocytes, plasma cells, macrophages > neutrophils and eosinophils).

Question 28

Physiological process that can lead to zone three necrosis

Answer 28

Chronic hypotension