cholestasis of pregnancy

1. Cholestasis
of Pregnancy
Dr Nishma Bajracharya
FCPS 2nd Year Resident

2. Introduction
Obstetric cholestasis (Intrahepatic Cholestasis of Pregnancy ICP) is a
multifactorial condition of pregnancy characterized by pruritus in the
absence of a skin rash with abnormal liver function tests (LFTs), and
both of which resolve after birth.
Usually occurring in the last trimester of pregnancy. It can, however,
occur earlier in gestations.
Second most common cause of jaundice in pregnancy, first- viral
hepatitis
• RCOG, Guideline , 2011

3. Background
• Prevalence is influenced by genetic and environmental factors and
varies between populations worldwide .
• In England, obstetric cholestasis affects 0.7% of pregnancies in
multiethnic populations and 1.2–1.5% of women of Indian–Asian or
Pakistani–Asian origin.
• In Chile, 2.4% of all pregnancies are affected .
• In India:- 5% of all pregnancies are affected .

4. Pathogenesis

5. • Genetic mutations in the hepatocellular transport protein ABCB4
which controls secretion of phosphatidylcholine into bile.
• Genetic changes to bile salt transport molecules, high levels of
estrogen glucuronides have been shown to inhibit the bile salt export
pump (BSEP) ABCB11, and high levels of sulfated progesterone
metabolites to inhibit the ABCB4 (MDR3) phospholipid transporter.
• limited studies have shown the role of selenium deficiency. Selenium
acts as a cofactor of several enzymes in the oxidative metabolism in
the liver but the role of selenium in bile secretion has yet to be
defined.
• Seasonal variation is also noted, with more severe cases in the winter
months.

6. Risk Factors
1. Personal or family history of obstetric cholestasis.
2. Multiple pregnancy.
3. Carriage of hepatitis C.
4. Presence of gallstones.

7. Clinical Presentation
1. Unexplained pruritus and Abnormal (LFTs) and/or
2. Raised bile acids.
Other causes of itching and of liver dysfunction should be excluded.
Postnatal resolution of pruritus and abnormal LFTs should be confirmed.
• RCOG, Guideline , 2011

8. • Pruritus of Pregnancy - is common, affecting 23% of pregnancies, of
which a small proportion will have obstetric cholestasis.
Pruritus of Cholestasis is
1- worse at night
2- often widespread and may involve the palms of the hands and/or
the soles of the feet.
Other evidence of cholestasis should be sought, including pale stool,
dark urine and jaundice.
Other causes of pruritus must be excluded such as eczema or atopic
eruption of pregnancy.

9. • If a rash is present, polymorphic eruption of pregnancy or
pemphigoid gestations (blisters) should be considered.

10. Jaundice
• Approximately, 2 weeks later, clinical jaundice will develop in 50 % of
cases.
• The jaundice is usually mild, soon plateaus, and remains constant
until delivery.
• The pruritus worsens with the onset of jaundice, and the patient's
skin can become excoriated.
• The symptoms usually abate within 2 days after delivery.

11. Laboratory abnormalities
Unexplained abnormalities in
1- Transaminases,
2-Gamma-Glutamyl Transferase
3 Bile salts
are considered sufficient to support the diagnosis of obstetric cholestasis.
Alkaline phosphatase (non specific as it is placental in origin so, it is not reflect liver
disease).
Bilirubin is raised only infrequently.
The most specific and sensitive marker of ICP is total serum bile acid (BA) levels
greater than 10 micromol/L Pregnancy-specific reference
ranges for LFTs should be used
(20% of non pregnant value)

12. Other causes of pruritus and abnormal LFTs should be sought:-
1. viral screen for hepatitis A, B, and C, EBV, CMV.
2. primary biliary cirrhosis (for example, anti-smooth muscle and
antimitochondrial antibodies). (liver ultrasound)
3. Pre-eclampsia and acute fatty liver of pregnancy are pregnancy-
specific causes of abnormal LFTs that might form part of the
differential diagnosis in atypical or early cases.

13. Maternal morbidity
1. Intense pruritus and Consequent sleep deprivation.
2. Increase Rate Of CS. (10-36%)
3. Increase Risk Of PPH.
4. If cholestasis lasts for several wks, liver dysfunction may
result in:
i. Decreased vitamin K re-absorption or
ii. Decreased prothrombin production, leading to a
prolongation of the prothrombin time.

14. Fetal risks
1. Preterm Birth- Spontaneous 4-12 % vs iatrogenic 7-25 %
2. Meconium Passage- More common in cases with severe
cholestasis compared with mild (10% vs with 0 %)
3. Still Birth.
4. Perinatal Mortality.

15. Monitoring
• Measure LFTs weekly until delivery
• If LFTs return to normal, obstetric cholestasis is not likely to be the
correct diagnosis.
• If LFTs escalate very rapidly, additional diagnoses need to be
considered and the frequency of monitoring increased.
• A coagulation screen should be performed.
• blood pressure measurement and urine check, allow monitoring of
the condition and exclusion of other diagnoses.
RCOG, Guideline , 2011

16. Can fetal death be predicted and prevented?
• Poor outcome cannot currently be predicted by biochemical results
and delivery decisions should not be based on results alone.
• No specific method of antenatal fetal monitoring for the prediction of
fetal death can be recommended.
• Ultrasound and CTG are not reliable methods for preventing fetal
death in cholestasis.
• Continuous fetal monitoring in labour should be offered.
• Fetal death is usually sudden. There is no evidence of placental
insufficiency. Fetal growth restriction and oligohydramnios are not
features of the disease.
RCOG, Guideline , 2011

17. Management
• A discussion should take place with women regarding induction of
labour after 37+0 weeks of gestation.
• Women should be informed of the increased risk of perinatal morbidity
from early intervention (before 37+0 weeks of gestation).
• informed of the inability to predict stillbirth if the pregnancy continues.
• Informed that the case for intervention (after 37+0 weeks of gestation)
may be stronger in those with more severe biochemical abnormality
(transaminases and bile acids).
• IOL at 38 weeks, in those with hyperbilirubinemia and fetal lungs
mature delivery at 36 weeks
Progress in Obs/ Gyne- 16
RCOG, Guideline , 2011

18. Treatment
RCOG, Guideline , 2011
There is no evidence that any specific treatment improves fetal or
neonatal outcomes.
Topical emollients calamine lotion and aqueous cream with menthol).
Safe but their efficacy is unknown

19. Systemic treatments
• Aim:- relieve pruritus
1. Colestyramine.
2. Antihistamines such as chlorphenamine may provide some
but not significant impact on pruritus.
3. Activated charcoal and guar gum do not relieve pruritus.

20. Cholestyramine (Cholestran Pack 4 gm).
A total of 8 to 16 g/day in three to four divided doses
• an anion exchange resin which acts by binding bile acids in the gut, thereby
inhibiting the enterohepatic circulation and increasing fecal excretion of
bile acids.
• May improve pruritus in some women
• It may reduce the intestinal absorption of fat-soluble vitamins, thus
depleting the levels of vitamin K and increasing the risk of hemorrhage for
the mother and fetus
• No randomised trials and is not in clinical use .

21. S-adenosyl methionine
• There is insufficient evidence to demonstrate whether it is
effective for either control of maternal symptoms or for
improving fetal outcome
• It is not recommended
RCOG, Guideline , 2011

22. Ursodeoxycholic acid (UDCA)
• UDCA is a naturally occurring hydrophilic bile acid
• Improves pruritus and liver function.
• No robust data concerning protection against stillbirth and safety to the fetus or
neonate.
• It enhances bile acid clearance across the placenta, This may protect the
hepatocyte membrane from the damaging toxicity of bile salts.
• 600- 2000mg
RCOG, Guideline , 2011

23. Dexamethasone
• 10 mg orally for 7 days and then stopping over 3 days
• should not be first-line therapy for treatment of obstetric
cholestasis,
• The results are conflicting, with some improvement in symptoms
and biochemistry in some women.
RCOG, Guideline , 2011

24. Role of vitamin K
Obstetric cholestasis can result in:-
1. Reduced absorption of dietary fats due to failure of excretion of
bile salts into the GIT and reduced micelle formation.
2. Increased fat excretion affects the absorption of fat-soluble
vitamins including vitamin K
RCOG, Guideline , 2011

25. Vitamin K
• 5- 10 mg daily oral, aiming to improve both maternal and
neonatal levels, and therefore reduce postpartum haemorrhage
and fetal or neonatal bleeding
• The use of water-soluble vitamin K (menadiol sodium
phosphate) is indicated.
• Postnatal vitamin K must be offered to the babies in the usual
way

26. Recent updates- Use of Rifampicin
• Combined Ursodeoxycholic acid (UDCA) and rifampicin is 2nd line
treatment.
• Enhances bile acid detoxification as well as bilirubin concentration.
• Increase excretion of bilirubin glucuronides by increasing MRP2
expression.
• Phenobarbitone increases the excretion of bile salt.

27. Role of Progesterone Metabolites in diagnosis of
ICP
• Progesterone sulfate are prognostic indicator of ICP
• Sulfated progesterone metabolites (PM2DiS,PM3S and PM3DiS
are found to be increased in maternal serum during ICP.
• Furthermore, UDCA treatment reduces ICP associated elevation of
disulfated progesterone metabolites.

28. POSTNATAL
• LFTs should be deferred for at least 10 days postnatally (6-8 wks)
• In normal pregnancy, LFTs may increase in the first 10 days of the
puerperium.
• Postnatal resolution of symptoms and of biochemical abnormalities
is required to secure the diagnosis.
RCOG, Guideline , 2011

29. Recurrence
• Intrahepatic cholestasis tends to recur in subsequent
pregnancies, but the severity may vary from one pregnancy
to the next.
• In their Chilean study, Gonzalez et al. reported a recurrence
rate of 70 % in singleton pregnancies.

30. Summary

31. References
• Obstetric Cholestasis, Green–top Guideline No. 43 April 2011
• Intrahepatic cholestasis of pregnancy, Victoria Geenes and Catherine
Williamson World J Gastroenterol. 2009 May 7; 15(17): 2049–2066.
Published online 2009 May 7. doi: 10.3748/wjg.15.2049
• Hepatic, Biliary and Pancreatic Disorders of Pregnancy, Williams
Obstetrics, 24th Edition
• Progress in Obstetrics and Gynecology, 16

32. Thank you