Metabolic liver disease

Question 1

What does MASH stand for and what does it mean?

Answer 1

Metabolic dysfunction-associated steatohepatitis (MASH) is the advanced stage of MASLD

Question 2

Signs of MASH on liver biopsy

Answer 2

lobular inflammation
hepatocyte ballooning
progressive liver scarring (fibrosis)

Question 3

NAFLD pathology definition

Answer 3

> 5% hepatocytes expressing fat within them

Question 4

Causes of liver steatosis

Answer 4

NAFLD
Hepatitis C
Alcohol excess
Genetic disorders
Medications
Hypothyroidism
Other rarer causes

Question 5

Pathophysiology of NAFLD

Answer 5

eat too many calories
increase in visceral fat
adipocytes resistant to insulin
fat into portal circulation
fat taken up by liver cells

Question 6

What is the new name for NAFLD?

Answer 6

MASLD
metabolic dysfunction associated steatotic liver disease

Question 7

What is MetALD?

Answer 7

MASLD and alcohol excess

Question 7

What are patients with NASH/MASH at risk of?

Answer 7

hepatocellular carcinoma

Question 8

Name some liver decompensation events

Answer 8

ascites
variceal bleed
encephalopathy
hepatocellular carcinoma
synthetic failure

Question 9

What score is used to approximate how scarred the liver is?

Answer 9

FIB-4
high number = lots of scarring

Question 10

What are Iron (II) compounds called?

Answer 10

ferrous

Question 11

What are Iron (III) compounds called?

Answer 11

ferric

Question 12

What is organic iron called?

Answer 12

haem

Question 13

How does iron in the body exist?

Answer 13

incorporated into Hb
Myoglobin, enzymes, Fe/S clusters
haem-containing cytochromes
stored iron in form of ferritin/haemosiderin
plasma transferrin-bound iron

Question 14

How does body regulate iron levels?

Answer 14

by regulating absorption

Question 15

Where does most iron absorption occur?

Answer 15

duodenum

Question 16

What is transferrin saturation?

Answer 16

how saturated transferrin is with iron

Question 17

Iron overload blood results

Answer 17

high ferritin
high transferrin saturation (>45%)

Question 18

Iron deficiency blood results

Answer 18

low ferritin
low transferrin saturation (<16%)

Question 19

What are the 2 forms iron exists in?

Answer 19

inorganic/non-haem = Fe3+ = less soluble

organic/haem = Fe2+ = more soluble

to be soluble, ferric needs to be reduced to ferrous

Question 20

What enzyme reduces ferric to ferrous?

Answer 20

duodenal cytochrome b ferrireductase

enzyme is vitamin C dependent

Question 21

What does ferroportin do?

Answer 21

allows iron out of duodenum

Question 22

What are transferrins?

Answer 22

iron-binding blood plasma glycoproteins that control the level of free iron in biological fluids

Question 23

What can raised ferritin mean?

Answer 23

inflammation
if no infection/inflammation = iron overload

Question 24

Clinical sequelae of iron overload

Answer 24

pituitary - impaired growth, infertility thyroid - hypoparathyroidism heart - dilated cardiomyopathy, cardiac failure liver - hepatic cirrhosis pancreas - diabetes mellitus gonads - hypogonadism

Question 25

How is haemochromatosis inherited?

Answer 25

autosomal recessive

Question 26

Describe the inheritance patterns of haemochromatosis

Answer 26

Cys282Tyr homozygous = haemochromatosis Cys282Tyr + H63D compound heterozygous = haemochromatosis H63D homozygote = does not cause haemochromatosis

Question 27

What is the natural progression of hereditary haemochromatosis?

Answer 27

phase of latency biochemical expression (~20y): - increased serum iron, transferrin saturation + serum ferritin Clinical expression (~40-50y): - fatigue, arthritis, hepatomegaly, skin pigmentation, diabetes - evolution towards cirrhosis and carcinoma women generally present later as iron is lost in menstruation

Question 28

At what age is screening for haemochromatosis offered to potentially at risk individuals (FH)?

Answer 28

at 18

Question 29

Wilson's disease inheritance

Answer 29

autosomal recessive not homozygous - normally 2 different mutations

Question 30

How is copper excreted?

Answer 30

in bile

Question 31

Wilson's disease treatment

Answer 31

copper-chelating drug: - penicillamine - trientine binds to copper so you pee it out occasionally transplant needed --> mutation is in liver so transplant is curative

Question 32

Signs of Wilson's disease

Answer 32

Kayser-Fleischer rings Parkinsonism Cirrhosis due to copper building up in areas of body

Question 33

Blood results in Wilson's

Answer 33

low caeruloplasmin total copper is low (free copper is high but caeruloplasmin with copper bound to it is very low so this makes total copper low)

Question 34

What is present in urine in Wilson's disease?

Answer 34

copper high in urine measure over 24 hours

Question 35

How is Wilson's disease diagnosed?

Answer 35

DNA sequencing looking for 2 pathogenic mutations liver biopsy + measure copper --> >250 micrograms/g = Wilson's

Question 36

Pathogenesis of Wilson's disease

Answer 36

mutations in ATP7B gene on chromosome 13 this gene makes an enzyme that is involved in copper transport when the enzyme is mutated, copper accumulated in liver and brain and becomes toxic

Question 37

Alpha-1-Antitrypsin deficiency inheritance

Answer 37

autosomal codominant

Question 38

When pink globules are seen on liver biopsy, what does this indicate?

Answer 38

alpha-1-antitrypsin deficiency