Obstetric Cholestasis & Acute Fatty Liver

Question 1

What is obstetric cholestasis?

Answer 1

• reduced outflow of bile acids from the liver
• resolves after delivery of the baby
• thought to be due to a rise in oestrogen + progesterone

Question 2

When does obstetric cholestasis typically present?

Answer 2

• it occurs later in pregnancy (after 28 weeks)
• this is within the third trimester

Question 3

Who is more at risk?

Answer 3

women of South Asian ethnicity

Question 4

What is the pathophysiology involved in obstetric cholestasis?

Answer 4

• bile acids are produced in the liver from the breakdown of cholesterol
• they flow past the gallbladder and out of the bile duct into the intestines
• in OC, this outflow is reduced
• this causes the bile acids to build up in the blood

Question 5

What severe risk is increased in OC?

Answer 5

increased risk of stillbirth

Question 6

What is the main symptom of OC?

Answer 6

severe pruritus

• this particularly affects the palms of the hands + soles of the feet

Question 7

What other symptoms may occur due to outflow obstruction in the bile ducts?

Answer 7

• fatigue
• dark urine
• pale, greasy stools
• jaundice

Question 8

What is “cholestasis”?

Answer 8

• reduced or stopped bile flow
• instead of entering the duodenum, the bile builds up in the liver
• eventually, this results in bile acids entering the bloodstream

Question 9

What rash is associated with obstetric cholestasis?

Answer 9

• there is NOT a rash associated with this condition
• if a rash is present, consider another condition:
  • pemphigoid gestationis
  • polymorphic eruption of pregnancy

Question 10

What is polymorphic eruption of pregnancy?

Answer 10

• an itchy, bumpy rash that starts in the stretch marks of the abdomen
• occurs in the last 3 months of pregnancy
• more common in a first pregnancy

Question 11

What is pemphigoid gestationitis?

Answer 11

• a rare pregnancy-associated autoimmune blistering skin condition
• tends to develop in the second or third trimester (13-40th week)
• starts as an itchy rash** that then **develops into blisters

Question 12

What other causes of pruritus should be excluded?

Answer 12

• gallstones
• acute fatty liver
• autoimmune hepatitis
• viral hepatitis

Question 13

What are the initial investigations for women presenting with pruritus?

Answer 13

• LFTs
• bile acids

Question 14

How will OC present when LFTs / bile acids are checked?

Answer 14

Bile acids:

• will be raised

LFTs:

• ALT, AST & GGT will be deranged

Question 15

Why is ALP not assessed during pregnancy?

Answer 15

• the placenta produces ALP
• it is NORMAL for ALP to be raised in pregnancy
• a rise in ALP without other abnormal LFT results is due to placental production, rather than liver pathology*

Question 16

What is the main treatment for obstetric cholestasis?

Answer 16

ursodeoxycholic acid

!! this does not improve the itching !!

Question 17

What treatments can be given to improve itching?

Answer 17

emollients such as calamine lotion

Question 18

What other medication may be given in OC?

Answer 18

• antihistamines such as chlorphenamine
• these can improve sleeping
• they DO NOT improve itching

Question 19

What can be given in OC if clotting is deranged?

Answer 19

water-soluble vitamin K

Question 20

Why can vitamin K deficiency occur in cholestasis?

What can this lead to?

Answer 20

• vitamin K is a fat-soluble vitamin
• a lack of bile in the intestines reduces fat absorption, and hence, absorption of vitamin K
• vit K is involved in the clotting system
• deficiency can result in impaired clotting of the blood

Question 21

What is involved in the monitoring of OC during pregnancy?

Answer 21

• LFTs should be monitored weekly

AND

• at least 10 days after delivery

Question 22

When might planned delivery be considered in OC?

Answer 22

• planned delivery after 37 weeks is considered when LFTs / bile acids are severely deranged
• stillbirth in OC is difficult to predict
• early delivery can reduce this risk

Question 23

What is acute fatty liver of pregnancy?

Answer 23

• rapid accumulation of fat within the hepatocytes
• this causes an acute hepatitis
• there is risk of liver failure / mortality for the mother + foetus

Question 24

When does acute fatty liver occur?

Answer 24

third trimester

Question 25

Why does acute fatty liver occur?

Answer 25

• there is impaired processing of fatty acids in the placenta
• this is due to a genetic condition in the fetus that impairs fatty acid metabolism

Question 26

What is the most common genetic cause of impaired fatty acid metabolism?

Answer 26

LCHAD deficiency

• (long-chain 3-hydroxyacyl-CoA dehydrogenase)*
• this is an autosomal recessive condition
• the mother also possesses one defective copy of the gene

Question 27

How can LCHAD deficiency result in acute fatty liver of pregnancy?

Answer 27

• LCHAD is important in fatty acid oxidation
• this allows them to be broken down + used for energy
• the fetus + placenta cannot break down fatty acids
• the fatty acids enter maternal circulation and accumulate in the liver
• accumulation of fatty acids leads to inflammation + liver failure

Question 28

How does acute fatty liver present?

Answer 28

vague symptoms associated with hepatitis:

• N&V
• jaundice
• generalised fatigue
• abdominal pain
• lack of appetite (anorexia)
• ascites
• hypertension

Question 29

What investigations are performed in acute fatty liver?

Answer 29

LFTs show raised liver enzymes (ALT / AST)

Question 30

What other blood tests may be deranged in acute fatty liver?

Answer 30

• raised bilirubin
• raised WCC
• deranged clotting (raised PTT + INR)
• low platelets

Question 31

What other condition can present with similar blood results to acute fatty liver?

Answer 31

HELLP syndrome

• they both present with low platelets + elevated liver enzymes
• HELLP syndrome is much more common

Question 32

What is the management for acute fatty liver of pregnancy?

Answer 32

• it is an OBSTETRIC EMERGENCY
• it requires prompt delivery of the baby
• treatment for acute liver failure +/- transplant may also be considered