Obstetric cholestasis and AFLP

Question 1

What is obstetric cholestasis? (OC)

Answer 1

OC is a liver disease of pregnacy usually occurring in the 3rd trimester.
Characterised by pruritis without rash and increased concentrations of serum bile acids in pregnancy, an dusually with increased concentrations of serum transaminases (occasionally with jaundice) in the absence of other liver pathology.
It resolves after birth.

Question 2

What is the association between obstetric cholestasis and estrogen?

Answer 2

OC usually appears when placental oestrogen synthesis is at its highest (3rd trimester) and resolves soon after birth.

Question 3

Define severe OC?

Answer 3

Serum bile acids > 40micromoles/L

Question 4

What are the risks associated with severe OC?

Answer 4

Increased fetal morbidity and mortality including:
- Preterm birth (25% vs 6.5%)
- NICU admission (12% vs 5.6%)
- Intrauterine fetal death (1.5% vs 0.5%)
! stillbirths usually occur after 38 weeks with littel or no warning.
Increased likelihood of meconium passage in pregnancies.

Question 5

Describe the timing, onset and location of pruritis in OC?

Answer 5

Pruritis = cardinal symptoms.
usually occurs from around 28 weeks, esp in multiple pregnancy
Typically on hands + feet spreading the extremities and trunk, w/o rash.

Question 6

Aside from pruritis, what other history may a women with OC report?

Answer 6

sleep disturbance due to pruritis
Dark urine, pale stools (uncommon)
Jaundice +/- steatorrhoea (usually 2-4 weeks after onset of pruritis) (rare)
Malaise + anorexia (occasional)
Previous pregnancies complicated by pruritis.
PHx of gallstones and/or of pruritis while taking the oral contraceptive pill
FHx of OC or pruritis in pregnnacy and/or gallstones

Question 7

How do you dx OC?

Answer 7

Raised bile acids (> 10micromoles/L) usually confirm the dx in the absence of other hepatic disease. BA > 15 micromoles/L = diagnostic.

A rise in serum transaminases is usually seen but not diagnostic.

Question 8

What other biochemical abnormalities may be apparent?

Answer 8

Raised transaminases and bilirubin rare

PT/INR prolonged in severe cases.

Question 9

Are bile acids always elevated with OC?

Answer 9

No. Normal values for serum BA and transaminases may occasionally be seen, with progressiont o abnormal alues over time. Women with persisting pruritus and normal bile acids/ALT should have repeat tests every 1-2 weeks.

Question 10

What imaging would you request for a woman being worked up for OC?

Answer 10

US KUB to exclude obstructive gallbladder disease and establish gallstones.

Question 11

What are DDx for OC?

Answer 11

Other liver disease, alcohol or other drug dependence.
consider viral hepatitis (esp if jaundice or dark urine present): check viral serology, including HAV, HBV, HCV, CMV, and EBV.
Autoimmune liver disease
Genetic causes (BRIC, PFIC)
PUPPP syndrome or polymorphic eruption of pregnancy and papular dermatitis -» papules and plaques with itching.
PET + HELLP syndrome: (can co-exist with OC)
Gallstones
Primary biliary cirrhosis (antimitochondrial ab +)
Chronic active hepatitis (antismooth muscle ab +)

Question 12

What are some risk factors for OC?

Answer 12

HCV, multiple pregnancies.

Question 13

what are some genetic causes of cholestasis?

Answer 13

Benign recurrent intrahepatic cholestasis (BRIC)

Progressive familial intrahepatic cholestasis (PFIC)

Question 14

When excluding secondary causes of liver dysfunction, what invx would you request and why?

Answer 14

Anti-smooth muscle antibodies (chronic hepatitis)
Anti-LKM antibodies (chronic hepatitis)
Anti-mitochondrial antibodies (primary biliary cirrhosis)

Question 15

Describe the role of daily external fetal monitoring in obstetric cholestasis?

Answer 15

No proven benefit. studies have reported intrauterine fetal deaths following a normal CTG tracing (within 7 hours to 5 days) in the presence of documental normal fetal activity in the hours before the dx of IUFD a/w OC.

Question 16

What pharmacological management do you use for OC?

Answer 16

Ursodeoxycholic acid (UDCA) has been shown to reduce pruritis (?degree of benefit may be small?)
No evidence to show reduction in stillbirth/severe perinatal morbidity 

Use of UDCA may be used if dx remote from term to improve maternal symptoms and liver function.

250mg TDS (mild cases)
500mg TDS (severe cholestasis i.e. BA > 40micromoles/L) and increase up to 750mg three to fourt imes a day (depending on symptoms + biochemistry)

SA guideline

Question 17

Women who fail to respond to UDCA can be considered for which other pharmacological therapy?

Answer 17

Rifampicin 300mg BD (a recognised inducer of liver enzyme metabolism)

SA guideline

Question 18

Which anti-histamines may be useful in alleviating pruritis in women with OC?

Answer 18

cetirizine 10mg 1-2 times a day

Promethazine 25mg at night according to medical prescription

Question 19

What would you offer if a women with OC has prolonged PT/INR?

Answer 19

vit K

Question 20

Which emollients could you offer women with OC symptomatic relief of pruritis?

Answer 20

sorbelene lotion, pinetarsol solution, aqu cream with menthol or bicarbonate of soda baths (symptomatic relief)

SA guideline

Question 21

A women has mild OC. What invx would you request and how often?

How would this change if she had severe OC? Prior to IOL?

Answer 21

Qweekly serum BA in mild cases, twice weekly in severe cases.
weekly and twice weekly LFTs in mild + severe cases
Coags after dx of severe OC and prior to IOL.

Question 22

A women has severe OC (i.e. ALT > 200, serum BA > 40 micromoles/L), when would you consider induction?

What things would you want to ensure for the IOL for a women with severe OC?

Answer 22

consider delivery at around K38 if serum BA and LFTs remain high (i.e BA > 40, ALT > 200)

Consider earlier delivery if BA > 100.

Continuous CTG
Coags prior to induction
Active mng of 3rd stage (as increased risk of PPH secondary to malabsorption of vit K)

Question 23

How would you cousel a women with OC on the resolution of symptoms in the postpartum period?

Answer 23

Pruritis will usually disappear 1-2 days after birth.
Jaundice usualy resolves in the 1st week.
Serum BA concentrations should normalise within the first week.
Exclude underlying liver disease if biochemical abnormalities persist beyond 6 weeks postpartum

Question 24

A women as OC in her first pregnancy. What is the risk of recurrence in subsequent pregnancies?

Answer 24

risk of recurrence is 40-60%

Question 25

What f/u do you recommend for a women who had OC in her pregnancy?

Answer 25

GP r/v of serum BA and LFTs in 1 month.

Exclude secondary causes of elevated LFTs if persisting.

Question 26

What is the maternal risk of OC?

Answer 26

Vit K deficiency leading to PPH

Question 27

What invx would you request for OC?

Answer 27

LFTs (use pregnancy specific ranges)
Clotting screen
BA
US of liver + biliary tree
Viral serology (HAV, HBV, HCV, CMV, EBV)
Auto-immune screen (anitmitochondiral and antismooth muscle antibodies)

Question 28

What are the clinical features of AFLP? (7)

Answer 28

Abdo pain
N/V
Jaundice 
Headahce 
Fever
confusion
coma

Question 29

What is the diagnostic criteria used for diagnosing AFLP?

Answer 29

Swansea criteria.

Question 30

What are the severe outcomes of AFLP for the mum?

Answer 30

Can progress rapidly to fulminant liver failure; DIC and renal failure.

Question 31

How do you differentiate AFLP from HELLP?

Answer 31

Distinctive features of AFLP:
Mild HTN and proteinuria only.
Early coagulopathy
Profound and persistent hypoglycaeia
Marked hyperuricaemia (i.e. uric acid or urate)
Fatty infiltration on imaging the liver (may also be normal)

Question 32

Mng of AFLP.

Answer 32

Correction of hypoglycaemia
Correction of coagulopathy with IV vit K and FFP
Strict control of BP and fluid balance.
Delivery should follow stabilisation
NB: regional anaesthesia is contraindicated if plts < 80 and deranged clotting.

Question 33

Mng of AFLP.

Answer 33

Correction of hypoglycaemia
Correction of coagulopathy with IV vit K and FFP
Strict control of BP and fluid balance.
Delivery should follow stabilisation
NB: regional anaesthesia is contraindicated if plts < 80

Question 34

Causes of jaundice in pregnancy (not specific (8) and specific to pregnancy (4))

Answer 34

Not specific to pregnancy?

1. Haemolysis
2. Gilbert’s syndrome
3. Viral hepatitis
4. Autoimmune hepatitis (primary biliary cirrhosis, chronic active hepatitis, sclerosing cholangitis)
5. Cirrhosis
6. Gallstones
7. Drug-induced hepatotoxicity
8. Malignancy.

Causes specific to pregnancy (10%)

1. Hyper-emesis gravidarum
2. PET/HELLP
3. AFLP
4. OC