15.3 Pathology: Patterns of liver injury 2

Question 1

What conditions aren’t classified as chronic hepatitis?

Answer 1

NASH, alcoholic liver disease

Question 2

What is the clinical definition of chronic hepatitis? What are the most common causes?

Answer 2

Persistence of liver injury, raised aminotransferase levels >6months (HBV, HCV)

Question 3

What proportion of patients infected with HCV will develop chronic disease?

Answer 3

80% (20% will develop cirrhosis)

Question 4

What is the difference between acute and chronic hepatitis?

Answer 4

Both:
T LCs (inflammatory infiltrate)

Difference in injury pattern

Acute: pan-lobular hepatocellular injury

Chronic: Inflammation in portal tracts and periportal liver tissue (associated w/ injury of periportal hepatocytes- LC and plasma cells)

Question 5

What is interface hepatitis?

Answer 5

• Key feature of chronic hepatitis*
• Periportal inflammation accompanied by lymphoplasmacytic inflammation and liver cell death (principally by apoptosis)

(amount is known as the ‘grade’ of chronic hep)

Question 6

Clinical vignette:

Patient has longstanding elevated ALT, chronic hepatitis C.

What kind of hepatitis will we see under microscopy?

Answer 6

Interface hepatitis (periportal inflammation accompanied by death of hepatocytes by apoptosis)

Question 7

Do we see lobular changes in chronic hepatitis?

Answer 7

Commonly present, usually mild.

Apoptotic bodies

(if severe, may look like acute hepatitis)

Question 8

What happens with fibrosis in chronic vs. acute hepatitis?

Answer 8

Chronic: fibrosis, can be progressive, resulting in cirrhosis

(fibrosis is absent in acute hep)

Question 9

Under microscopy what do we see in chronic hepatitis?

Answer 9

Fibrous septa (using a masson trichome stain, collagen stains blue) aka scar tissue

Question 10

What cell produces the fibrosis in chronic liver disease?

Answer 10

Cytokine induced activated hepatic stellate cell (become like myofibroblasts, produce more collagen)

Question 11

What are the stages of fibrosis?

Answer 11

Stage 1: enlarged portal tracts, no septa
Stage 2: septa, not much linking b/w portal tracts
Stage 3: portal to portal bridging
Stage 4: cirrhosis

Question 12

What damages liver cells in alcoholic liver disease?

Answer 12

Acetaldehyde (hepatocellular damage)

Oxidative stress

Question 13

What are the histological changes in alcoholic liver disease?

Answer 13

• Fatty change (reversible, abnormal accumulation of lipid in hepatocytes)
• Alcoholic steatohepatitis (leads to hepatocellular death and fibrosis)
• Progressive fibrosis leading eventually to cirrhosis

Question 14

What is the difference between steatosis vs. steatohepatitis?

Answer 14

Steatohepatitis: fat + hepatocellular injury (ballooning-swelling and formation of Mallory-Denk bodies)

Question 15

What are Mallory-Denk bodies?

Answer 15

Characteristic of ALD, collapse of hepatic cytoskeleton

look like swollen, ropey hepatocytes

Question 16

What are the features of alcoholic steatohepatitis?

What can it be misdiagnosed as?

Answer 16

If severe: jaundice, fever, hepatomegaly, impared liver function, leucocytosis (disease has 50% 30 day mortality)

Misdiagnosis as a surgical problem e.g. cholecystisis (very bad to operate on these patients)

Question 17

What do you see in histological section of alcoholic liver disease? (regarding fibrosis)

Answer 17

Fibrosis (differs), surrounds vein, groups of cells esp. in the zone 3 parenchyma
‘chicken wire fibrosis’

Question 18

What is non-alcoholic fatty liver disease? How can we differentiate ALD from NAFLD?

Answer 18

Similar to histology of alcoholic except not usually severe (less common: steatohepatitis w/ numerous Mallory bodies)

Distinction is made via clinical examination/history (often associated w/ obesity, metabolic syndrome and diabetes)

Question 19

What is NASH? What do we see?

Answer 19

Non-alcoholic steatohepatitis, seen in NAFLD

See hepatocellular ballooning

Question 20

What is the natural history of NAFLD?

Answer 20

Either isolated fatty liver (low risk, minimal progression to cirrhosis)

OR

NASH (leading to decompensation or hepatocellular carcinoma)