Intrahepatic cholestasis of pregnancy (ICP) is a reversible liver disorder that occurs during late pregnancy and is characterized by severe pruritus without skin lesions. It is caused by hormonal changes that inhibit bile salt transporters in the liver. ICP can lead to fetal complications like death, preterm delivery, and meconium staining. Management involves monitoring, supportive care, ursodeoxycholic acid, and early delivery at 37 weeks to prevent fetal risks. Maternal outcomes are generally good but symptoms often recur in subsequent pregnancies.

1. B Y:
PAWA N K B AG R AWAL
R E S I D E N T M D G P, Y E AR I I , I O M M AH A R A J G U N J .
2 N D J U N E , 2 0 1 5 .
M O D E R ATO R : D R . R AJ E S H AD H I K A R I
INTRAHEPATIC CHOLESTASIS
OF PREGNANCY

2. OUTLINE
• Rationale
• Introduction
• Epidemiology
• Risk factors
• Pathogenesis
• Clinical presentation
• Differentials
• Investigations
• Morbidity/Mortality
• Management
• Implications
• Conclusion
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3. RATIONALE
• It is the most common pregnancy related liver
disorder (1).
• Approximately 1 % of pregnancies in the U.S.
are complicated by this condition while the
prevalence is approximately double in South
Asia region (2).
• Tricky. Maternal outcomes are often good.
However, fetal outcomes may be devastating.
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4. INTRODUCTION
• Also known as icterus gravidarum, cholestatic
hepatosis & recurrent jaundice of pregnancy.
• Defined as reversible type of hepatic dysfunction
induced by hormonal changes in late pregnancy
& clinically characterized by generalized pruritis
often commencing on palms & soles in absence
of visible skin lesions.
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5. EPIDEMIOLOGY
• Common in South Asia, South America & the
Scandinavian countries (1).
• High incidence in Latin America . 4% in Chile (4).
• Has seasonal variation. More frequent in winters
(1).
• Appears in late second trimester or third
trimester secondary to peak in estrogen
concentrations.
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6. RISK FACTORS
• Advanced maternal age.
• History of cholestasis with COC.
• Multiple pregnancies.
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7. PATHOGENESIS
Genetic Susceptibility. ABCB 4 gene
Inadequate excretion of bile salts : inhibition of
hepatocellular bile salt export pumps or
saturation by sulfated progesterone metabolites
Increased serum bile salts : taurocholate &
taurodeoxycholate.
Deposition in skin
Intense pruritis
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8. CLINICAL PRESENTATION
• Generalized pruritis starting from the palms &
soles progressing to trunk & face.
• Skin lesions often absent and limited to
excoriations.
• Worse at night.
• Only 10% develop jaundice (3). Typically
develops 1-4 weeks after onset of itching (1) .
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9. DIFFERENTIALS
1. Pruritis gravidarum
2. Choledocholithiasis
3. Preeclampsia
4. Dermatoses
1. Pemphigoid gestationis
2. Pruritic urticarial papules and plaques of pregnancy
3. Atopic eruption of pregnancy
4. Pustular psoriasis of pregnancy
5. Viral hepatitis
6. Acute fatty liver of pregnancy
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10. DIFFERENTIALS
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11. DIFFERENTIALS
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12. DIFFERENTIALS
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13. DIFFERENTIALS
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14. INVESTIGATIONS
• LFTs (3)
• For transaminases,gamma-glutamyl transferase
and bilirubin, the upper limit of normal throughout
pregnancy is 20% lower than the non-pregnant
range (6).
• Serum aminotransferase levels are normal to
moderately elevated and seldom exceed 250 U/L.
• Conjugated hyperbilirubinemia with total bilirubin
often less than 4-5 mg/dl .
• Alkaline phosphatase is increased up to 4 fold (1).
• PT reflects Vit K status.
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15. INVESTIGATIONS
• Viral screen
• Hepatitis A, E, B & C
• EBV &
• CMV
• USG abdomen
• To rule out choledocholithiasis
• Obstetric scan for fetal well being.
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16. INVESTIGATIONS
• Bile acid levels (1)
• The most sensitive & specific marker of ICP.
• Total serum bile acid level greater than 10 μmol/L.
• The cholic acid level is significantly increased while
the chenodeoxycholic acid level is mildly increased.
• Liver biopsy
• Not recommended
• Shows bile plugs without evidence of inflammation and
bile pigment in hepatocytes.
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17. MORBIDITY/ MORTALITY
• Rook and colleagues (2012) reported outcomes
of 101 affected women in Northern California.
• Although there were no term fetal demises,
87percent of women underwent labor induction.
• Neonatal complications occurred in a third of the
pregnancies, particularly respiratory distress,
fetal distress, and meconium-stained amniotic
fluid, all of which were reported more frequently
with higher total bile acid levels.
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18. MORBIDITY/ MORTALITY
• Fetal:
• The risk of fetal demise range from 2-11% .But
rarely occurs prior to 36 weeks of gestation (1).
Increased risk with bile acids >40 μmol/L or
presence of jaundice. (Attributed to 1) transfer of bile acids
across placenta, into cardiomyocytes & causing arrythmias 2) fetal
anoxia & 3) vasoconstriction of chorionic veins)
• Preterm delivery (mostly due to surgeon’s distress and
spontaneous ones have been hypothesized due to increased myometrial
contractions sec to bile salt depositions)
• Fetal distress & meconium staining of liquor in a
third of affected pregnancies (3).
• Neonatal respiratory distress (bile salt deposition in fetal
lungs).
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19. MORBIDITY/ MORTALITY
• Maternal:
• Steatorrhoea
• Vitamin K deficiency
• PPH 2-22% (6) otherwise 4-6%.
• Cholestasis recurs in 60-70% of subsequent
pregnancies with variable severity.
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20. MANAGEMENT
• Concerns:
• sudden fetal death ,
• PPH &
• maternal discomfort.
• Supportive:
• Antihistaminics like cetirizine (cat B) and
topical emmolients can be used for
symptomatic relief but not much effective.
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21. MANAGEMENT
• Cholestyramine (8-16 g/day) has also been
used but causes further reduction in
absorption of fat soluble vitamins.
• Dexamethasone (10 mg OD for 7 days
followed by tapering over 3 days)
• Ursodeoxycholic acid starting at daily
doses of 300mg TDS has been the drug of
choice. Improves both clinical & lab
parameters. ? Better fetal outcome.
• Vit K in cases of prolonged PT
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22. MANAGEMENT
• Monitoring:
• Umbilical artery doppler twice-weekly superior
to NST .
• LFTs repeated weekly until delivery.
• Definite:
• Termination of pregnancy with induction at
37 weeks or prior to 37 weeks in cases of
excruciating & unremmitting pruritis after
confirmation of lung maturity.
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23. MANAGEMENT
• Follow up:
• Postnatal resolution of symptoms and of
biochemical abnormalities is required to
secure the diagnosis.
• Postnatal resolution of symptoms and of
biochemical abnormalities is required to
secure the diagnosis. Repeat LFT once in
postnatal follow up beyond 10 days.
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24. IMPLICATIONS/ASSOCIATIONS
• CDC considers combined pills appropriate in
women with ICP.
• Affected women are at increased risk of
developing gall stones
• Women with persistent pruritis and normal
LFTs should have it repeated every one to two
weeks.
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25. CONCLUSION
• ICP is a diagnosis of exclusion.
• Good maternal outcome. Fetal outcome may
be devastating.
• Genetic predisposition.
• UDCA is the first line treatment.
• Imperative to terminate pregnancy at 37
weeks.
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26. REFERENCES
1. Rigby FB. Intrahepatic cholestasiss of pregnancy.
2015; Available at:
URL:http://emedicine.medscape.com/article/1562288-
overview#showall. Accessed May 22, 2015.
2. James D. High risk pregnancy management options.
4th ed. Saunders; 2000.
3. Cunnigham et al . Williams obstetrics. 24th ed . Mac
Graw Hill ; 2014.
4. Dutta D.C. Textbook of obstetrics. 7th ed. New Central
Book Agency ; 2010.
5. Bacq Y, Lee RH. Cholestasis of pregnancy. 2011;
Available at:
URL:http://UpToDate19.3/contents/mobipreview.htm?1
5/62/16352#H1
6. Kenyon AP. Obstetric cholestasis. RCOG Green-top
Guideline No. 43.
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