Metabolic liver disease Flashcards
What does MASH stand for and what does it mean?
Metabolic dysfunction-associated steatohepatitis (MASH) is the advanced stage of MASLD
Signs of MASH on liver biopsy
lobular inflammation
hepatocyte ballooning
progressive liver scarring (fibrosis)
NAFLD pathology definition
> 5% hepatocytes expressing fat within them
Causes of liver steatosis
NAFLD
Hepatitis C
Alcohol excess
Genetic disorders
Medications
Hypothyroidism
Other rarer causes
Pathophysiology of NAFLD
eat too many calories
increase in visceral fat
adipocytes resistant to insulin
fat into portal circulation
fat taken up by liver cells
What is the new name for NAFLD?
MASLD
metabolic dysfunction associated steatotic liver disease
What is MetALD?
MASLD and alcohol excess
What are patients with NASH/MASH at risk of?
hepatocellular carcinoma
Name some liver decompensation events
ascites
variceal bleed
encephalopathy
hepatocellular carcinoma
synthetic failure
What score is used to approximate how scarred the liver is?
FIB-4
high number = lots of scarring
What are Iron (II) compounds called?
ferrous
What are Iron (III) compounds called?
ferric
What is organic iron called?
haem
How does iron in the body exist?
incorporated into Hb
Myoglobin, enzymes, Fe/S clusters
haem-containing cytochromes
stored iron in form of ferritin/haemosiderin
plasma transferrin-bound iron
How does body regulate iron levels?
by regulating absorption
Where does most iron absorption occur?
duodenum
What is transferrin saturation?
how saturated transferrin is with iron
Iron overload blood results
high ferritin
high transferrin saturation (>45%)
Iron deficiency blood results
low ferritin
low transferrin saturation (<16%)
What are the 2 forms iron exists in?
inorganic/non-haem = Fe3+ = less soluble
organic/haem = Fe2+ = more soluble
to be soluble, ferric needs to be reduced to ferrous
What enzyme reduces ferric to ferrous?
duodenal cytochrome b ferrireductase
enzyme is vitamin C dependent
What does ferroportin do?
allows iron out of duodenum
What are transferrins?
iron-binding blood plasma glycoproteins that control the level of free iron in biological fluids
What can raised ferritin mean?
inflammation
if no infection/inflammation = iron overload
Clinical sequelae of iron overload
pituitary - impaired growth, infertility
thyroid - hypoparathyroidism
heart - dilated cardiomyopathy, cardiac failure
liver - hepatic cirrhosis
pancreas - diabetes mellitus
gonads - hypogonadism
How is haemochromatosis inherited?
autosomal recessive
Describe the inheritance patterns of haemochromatosis
Cys282Tyr homozygous = haemochromatosis
Cys282Tyr + H63D compound heterozygous = haemochromatosis
H63D homozygote = does not cause haemochromatosis
What is the natural progression of hereditary haemochromatosis?
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
At what age is screening for haemochromatosis offered to potentially at risk individuals (FH)?
at 18
Wilson’s disease inheritance
autosomal recessive
not homozygous - normally 2 different mutations
How is copper excreted?
in bile
Wilson’s disease treatment
copper-chelating drug:
- penicillamine
- trientine
binds to copper so you pee it out
occasionally transplant needed –> mutation is in liver so transplant is curative
Signs of Wilson’s disease
Kayser-Fleischer rings
Parkinsonism
Cirrhosis
due to copper building up in areas of body
Blood results in Wilson’s
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)
What is present in urine in Wilson’s disease?
copper high in urine
measure over 24 hours
How is Wilson’s disease diagnosed?
DNA sequencing looking for 2 pathogenic mutations
liver biopsy + measure copper –> >250 micrograms/g = Wilson’s
Pathogenesis of Wilson’s disease
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
Alpha-1-Antitrypsin deficiency inheritance
autosomal codominant
When pink globules are seen on liver biopsy, what does this indicate?
alpha-1-antitrypsin deficiency
