L4: Liver Disease and Cirrhosis

Question 1

What tests/investigations are done to identify if there is steatosis in the liver?

Answer 1

• ultrasound

- liver blood tests (transaminases)

Question 2

What stain can be used to highlight fat droplets and visualize fatty change?

Answer 2

Oil Red O Stain

Question 3

What is Mallory’s Hyaline suggestive of?

Answer 3

alcohol-related steatohepatitis

Question 4

What is the pathogenesis of liver injury due to alcohol metabolism (liver injury in alcoholics)?

Answer 4

• fat synthesis stimulated
• free radicals generated via MEOS pathway
• acetaldehyde is toxic
• altered intracellular metabolism

Question 5

What is the MEOS pathway? When is it activated?

Answer 5

• induced in heavy drinkers

- produces more reactive/toxic intermediates

Question 6

What is the treatment for alcohol-related liver damage?

Answer 6

ABSTINENCE

- if really severe, steroids

Question 7

NAFLD is typically a/w with metabolic syndrome. What does metabolic syndrome entail?

Answer 7

obesity, T2DM, insulin resistance, high triglycerides, low HDL cholesterol

Question 8

What is the treatment for NAFLD?

Answer 8

• weight loss
• exercise
• treat underlying risk factors in metabolic syndrome

Question 9

A genetic defect in the HFE gene can lead to disease?

Answer 9

Hereditary (Primary) Haemochromatosis

Question 10

Which chromosome is the HFE gene located on?

Answer 10

chromosome 6p

Question 11

A mutation in HFE gene can lead to hereditary haemochromatosis. What are 2 mutations that may be present? What mutations are the most common

Answer 11

C282Y
H63D

most cases are C282Y/C282Y homozygotes

Question 12

Iron is transported in the blood by what?

Answer 12

Transferrin

Question 13

What will give the % saturation of iron which then will indicate the iron storage status?

Answer 13

Transferrin

Question 14

Iron has 2 storage forms which are:

Answer 14

Ferritin and Haemosiderin

Question 15

What is the function of Hepcidin?

Answer 15

• it blocks iron entry into the blood circulation from GIT
• inhibitory target = Ferroportin

if there is lack of hepcidin there will be lots of iron in the blood

Question 16

What does the HFE gene code for?

Answer 16

Hepcidin

Question 17

What is the treatment of haemochromatosis?

Answer 17

Venepuncture/Phlebotomy

Question 18

What stain is used to identify haemochromatosis? What does it typically stain for?

Answer 18

Perl’s Stain (Prussian Blue)

- stains for haemosiderin (iron storage form)

Question 19

What is the Kayser-Fleischer ring indicative of?

Answer 19

Wilson’s Disease - increase in copper in body

Question 20

What are the test values for Type 1 AIH?

Answer 20

ANA/SMA Positive

AMA Negative

Question 21

What are the test values for Type 2 AIH?

Answer 21

Anti-LKM Positive

Question 22

What is the treatment for AIH?

Answer 22

Immunosuppression (steroids, azathioprine)

Question 23

What are the test values for Primary Biliary Cirrhosis (PBC)?

Answer 23

• high Alk Phos
• elevated IgM
• AMA positive
• SMA negative

Question 24

What is the treatment for Primary Biliary Cirrhosis (PBC)?

Answer 24

• Ursodeoxycholic Acid (UDCA)
• symptomatic treatment
• OLT

not steroids!

Question 25

If PSC is intra-hepatic mainly what would it lead to?

Answer 25

progressive cholestasis going to cirrhosis

Question 26

If PSC is extra-hepatic mainly what would it lead to?

Answer 26

stricture with CBD obstruction, risk ascending cholangitis

Question 27

PSC has a strong associated with IBD and what in particular?

Answer 27

Ulcerative Colitis note: there is an increased risk of cholangiocarcinoma

Question 28

In advanced liver disease, there may be a failure of oestrogen inactivation and this may lead to:

Answer 28

- spider naevi - palmar erythema - gynaecomastia - testicular atrophy

Question 29

What criteria does the Child-Pugh score contain? What is it used for?

Answer 29

albumin, PT, bilirubin, ascites, HE used as a prognosis of cirrhosis

Question 30

What criteria does the MELD score contain? What is it used for?

Answer 30

PT, bilirubin, creatinine it rates the severity of liver disease to see how much the patient needs a liver transplant

Question 31

What is steatosis?

Answer 31

fatty change of the liver

Question 32

Is steatosis typically macrovesicular or microvesicular?

Answer 32

Macrovesicular

Question 33

What is steatohepatitis?

Answer 33

fatty change a/w inflammation

Question 34

What condition does MACROvesicular fatty change of the liver usually cause?

Answer 34

``` alcoholic syndrome and metabolic syndrome (NAFLD) ```

Question 35

What condition does MICROvesicular fatty change of the liver usually cause?

Answer 35

acute liver failure

Question 36

List some of the histological features of steatohepatitis

Answer 36

- lobular inflammation/necrosis (centered in zone 3 around hepatic vein) - neutrophils in inflammatory infiltrate - Mallory's hyaline (w/in hepatocytes) - perivenular fibrosis (around hepatic vein)

Question 37

Mallory's Hyaline may be suggestive of alcohol-related damage in the liver. How does it look like in histology?

Answer 37

- dense pink intracytoplasmic inclusions | - altered intracellular proteins

Question 38

Primary Sclerosing Cholangitis (PSC) on its own, increases the risk for which type of cancer?

Answer 38

Cholangiocarcinoma

Question 39

PSC which occurs in IBD patients, increases the risk for which type of cancer?

Answer 39

Colorectal Cancer