131 - Patterns of Liver Injury 2

Question 1

Conventions of nomenclature in chronic hepatitis
1
2

Answer 1

• By convention, alcoholic liver disease and NASH are not classified as “chronic hepatitis” although these are forms of chronic liver disease
• By convention, chronic inflammatory liver disease in which the bile ducts are the major targets are not classified as “chronic hepatitis” (primary sclerosing cholangitis and primary biliary cirrhosis)

Question 2

NASH

Answer 2

Non-alcoholic steatohepatitis

Question 3

Clinical definition of chronic hepatitis

Answer 3

Persistence of liver injury with raised serum aminotransferase levels > 6 months

Question 4

Most common causes of chronic hepatitis

Answer 4

Hep B and C

Question 5

Proportion of hep C patients who develop cirrhosis

Answer 5

~20%

Question 6

Most predominant inflammatory infiltrate in chronic and acute hepatitis

Answer 6

T lymphocytes

Question 7

Pattern of injury in acute hepatitis

Answer 7

The hallmark feature of acute hepatitis is predominantly pan-lobular hepatocellular injury.

Question 8

Pattern of injury in chronic hepatitis

Answer 8

Inflammation in the portal tracts and the periportal liver tissue

Associated with injury of the periportal hepatocytes (inflammatory cells are lymphocytes and plasma cells = mononuclear inflammation).

Question 9

Interface hepatitis

Answer 9

Periportal hepatocellular injury accompanied by lymphoplasmacytic inflammation

Question 10

Important determinant of the rate at which liver fibrosis occurs

Answer 10

Grade of chronic hepatitis (or degree of interface hepatitis)

Question 11

Unusual feature of acute inflammation in the liver

Answer 11

Inflammatory infiltrate is predominantly T lymphocytes, not neutrophils

Question 12

Lobular features in chronic hepatitis
1
2
3

Answer 12

• Commonly present, but usually mild.
• Apoptotic bodies.
• Can be severe and then the lobular changes look like acute hepatitis (especially seen in autoimmune hepatitis).

Question 13

How is chronic hepatitis with lobular disarray diagnosed?

Answer 13

Difficult for pathologists to distinguish between acute and chronic hepatitis unless the clinicians tells us or there is fibrosis.

Question 14

Hallmark feature of chronic hepatitis

Answer 14

Interface hepatitis.
Inflammation/death of portal hepatocytes.
This is not specific to chronic hepatitis.

Question 15

Fibrosis in acute vs chronic hepatitis

Answer 15

• Acute hepatitis – fibrosis is absent

* Chronic hepatitis – fibrosis may occur and can be progressive (resulting in cirrhosis)

Question 16

Histology of chronic hepatitis

Answer 16

Plasma cells, T lymphocytes surrounding periportal hepatocytes.
Death of hepatocytes, mostly by apoptosis.

Question 17

Cell types that can make fibrous tissue in chronic hepatitis
1
2

Answer 17

1) Portal fibroblasts

2) Hepatic stellate cells

Question 18

How do hepatic stellate cells contribute to fibrosis?

Answer 18

Cytokine induced hepatic stellate cell activation is central: proliferation and conversion into fibrogenic myofibroblasts.

Question 19

Where do hepatic stellate cells sit?

Answer 19

In the space of Disse.
Normally quiescent.
Undergo fibrogenic myofibroblast proliferation.

Question 20

Situation where you can get lobular changes with chronic hepatitis

Answer 20

If have a chronic hep B infection, and a superinfection with hep D (hep D can resemble acute hepatitis).

Question 21

Stage of chronic hepatitis

Answer 21

Degree of fibrosis in patient.
From 0 (normal) to 4 (cirrhosis)

Question 22

How is fibrosis identified in liver biopsies?

Answer 22

Masson trichrome stain stains collagen blue, hepatocytes stained red.

Look for fibrous (collagenous) septa.

Question 23

Fibrosis stage 1

Answer 23

Enlarged portal tracts, no septa

Question 24

Fibrosis stage 2

Answer 24

Enlarged portal tracts with septa.

Not much linkage of septa between portal tracts.

Question 25

Fibrosis stage 3

Answer 25

Enlarged portal tracts.

Linkage of septa between portal tracts.

Question 26

Fibrosis stage 4

Answer 26

Cirrhosis.

Extensive fibrosis

Question 27

Two basic functions of myofibroblasts

Answer 27

Contract, produce collagen

Question 28

Pathogenesis of alcoholic liver disease
1
2
3
4
5

Answer 28

• Hepatocellular damage from acetaldehyde
• Oxidative stress
• Impaired carbohydrate and fat metabolism
• Stimulation of collagen synthesis by alcohol
• Genetic susceptibility

Question 29

Histology of alcoholic liver disease
1
2
3

Answer 29

• Fatty change – abnormal accumulation of lipid in hepatocytes (reversible and does not cause hepatocellular death or fibrosis)
• Alcoholic steatohepatitis (leads to hepatocellular death and fibrosis)
• Progressive fibrosis leading eventually to cirrhosis

Question 30

Macrovesicular steatosis

Answer 30

Large fat vacuoles in periventricular hepatocytes.

Displace nuclei to edges of cells.

Question 31

Steatosis vs steatohepatitis
1
2
3

Answer 31

• Steatosis is the abnormal retention of lipids in cells
• Steatohepatitis is defined by the presence of fat + hepatocellular injury
• Hepatocellular injury is characterised by ballooning (swelling) and formation of Mallory-Denk bodies.

Question 32

Mallory-Denk bodies
1
2
3
4

Answer 32

• Characteristic of ALD but not specific.
• Collapse of the hepatic cytoskeleton.
• Intermediate filaments (cytokeratin 8 and 18) and other proteins including ubiquitin.
• Attract neutrophils

Question 33

Mortality of severe alcoholic steatohepatitis

Answer 33

If severe can cause “acute alcoholic hepatitis” which is a syndrome with features of jaundice, fever, hepatomegaly, markedly impaired liver function, and leucocytosis. This disease carries a 50% 30 day mortality.

Question 34

Spectrum of severity of alcoholic steatohepatitis

Answer 34

From asymptomatic to extremely severe acute alcoholic hepatitis.

Question 35

Features of steatohepatitis
1
2
3
4

Answer 35

1) Fat
2) Hepatocyte swelling (ballooning degeneration)
3) Mallory’s hyaline
4) Inflammation (often neutrophils)

Question 36

Non-alcoholic fatty liver disease
1
2
3

Answer 36

1) Major associations are obesity, metabolic syndrome and diabetes.
2) Histological spectrum the same as for alcoholic, although severe steatohepatitis with numerous Mallory bodies is much less common.
3) Distinction from alcoholic liver disease is essentially clinical rather than histologic (look pretty much the same pathologically)

Question 37

Difference in demographic between steatohepatitis and non-alcoholic fatty liver disease

Answer 37

Non-alcoholic fatty liver disease occurs in adults and children

Question 38

Histology of alcoholic steatohepatitis 
1
2
3
4

Answer 38

1) Inflammatory cells (mostly neutrophils)
2) Neutrophils cluster around, within hepatocytes
3) Some hepatocytes contain Mallory-Denk bodies
4) Many hepatocytes contain large fat vacuoles

Question 39

Pattern of fibrosis in alcoholic liver disease

Answer 39

Collagen surrounds individual hepatocytes.
Collagen begins around central veins.
‘Chicken wire fibrosis’

Question 40

Difference in patterns of fibrosis between chronic hepatitis and alcoholic liver disease

Answer 40

Chronic hepatitis fibrosis begins around portal triads.

Alcoholic liver disease fibrosis begins around central vein

Question 41

Difference in severity between alcoholic steatohepatitis and non-alcoholic fatty liver disease

Answer 41

Steatohepatitis more severe normally

Question 42

Signs of NAFLD

Answer 42

Steatosis with or without steaohepatitis and fibrosis.

Question 43

Difference between alcoholic steatohepatitis and non-alcoholic fatty liver disease

Answer 43

Difference in causative factors (EG: alcohol), but otherwise the same

Question 44

Natural history of NAFLD
1
2
3
4
5
6

Answer 44

1) Non-alcoholic fatty liver disaese
2) Over 80% have isolated fatty liver.
3) Rest go on to non-alcoholic steatohepatitis
4) ~11% over 15 years go on to cirrhosis
5) ~31% chance of decompensation over 8 years
6) ~7% go on to hepatocellular carcinoma over 6.5 years
7) Can progress from NASH straight to hepatocellular carcinoma

Question 45

Painful arc of movement with rotator cuff injury

Answer 45

~60 - 120 degrees of shoulder abduction

Question 46

Most common way in which shoulder is dislocated

Answer 46

Anterior and inferior.

Due to force applied to abducted and externally rotated arm

Question 47

How can posterior shoulder dislocations occur?

Answer 47

Epileptic fit, electric shock.

Less common than anterior dislocation.

Question 48

Possible outcome of shoulder dislocation

Answer 48

Axillary nerve (from the posterior cord of the brachial plexus) is in quadrangular space.

At risk of inferior dislocation.