Obstetric cholestasis and AFLP Flashcards
What is obstetric cholestasis? (OC)
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.
What is the association between obstetric cholestasis and estrogen?
OC usually appears when placental oestrogen synthesis is at its highest (3rd trimester) and resolves soon after birth.
Define severe OC?
Serum bile acids > 40micromoles/L
What are the risks associated with severe OC?
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.
Describe the timing, onset and location of pruritis in OC?
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.
Aside from pruritis, what other history may a women with OC report?
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
How do you dx OC?
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.
What other biochemical abnormalities may be apparent?
Raised transaminases and bilirubin rare
PT/INR prolonged in severe cases.
Are bile acids always elevated with OC?
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.
What imaging would you request for a woman being worked up for OC?
US KUB to exclude obstructive gallbladder disease and establish gallstones.
What are DDx for OC?
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 +)
What are some risk factors for OC?
HCV, multiple pregnancies.
what are some genetic causes of cholestasis?
Benign recurrent intrahepatic cholestasis (BRIC)
Progressive familial intrahepatic cholestasis (PFIC)
When excluding secondary causes of liver dysfunction, what invx would you request and why?
Anti-smooth muscle antibodies (chronic hepatitis)
Anti-LKM antibodies (chronic hepatitis)
Anti-mitochondrial antibodies (primary biliary cirrhosis)
Describe the role of daily external fetal monitoring in obstetric cholestasis?
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.
What pharmacological management do you use for OC?
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
Women who fail to respond to UDCA can be considered for which other pharmacological therapy?
Rifampicin 300mg BD (a recognised inducer of liver enzyme metabolism)
SA guideline
Which anti-histamines may be useful in alleviating pruritis in women with OC?
cetirizine 10mg 1-2 times a day
Promethazine 25mg at night according to medical prescription
What would you offer if a women with OC has prolonged PT/INR?
vit K
Which emollients could you offer women with OC symptomatic relief of pruritis?
sorbelene lotion, pinetarsol solution, aqu cream with menthol or bicarbonate of soda baths (symptomatic relief)
SA guideline
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?
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.
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?
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)
How would you cousel a women with OC on the resolution of symptoms in the postpartum period?
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
A women as OC in her first pregnancy. What is the risk of recurrence in subsequent pregnancies?
risk of recurrence is 40-60%
