13. intrahepatic cholestasis of pregnancy3rd jun 15

BY:

PAWA N K B A GR AWA LR E S I D E N T M D G P, Y E A R I I , I OM M A H A R A J GU N J .

2 N D J U N E , 2 0 1 5 .MO D E R AT OR : D R . R A J E S H A D H I K A R I

INTRAHEPATIC CHOLESTASIS OF

PREGNANCY

OUTLINE

• Rationale• Introduction• Epidemiology• Risk factors• Pathogenesis• Clinical presentation• Differentials• Investigations• Morbidity/Mortality• Management• Implications• Conclusion

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-15Intrahepatic Cholestasis of Pregnancy by Paw

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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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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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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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RISK FACTORS

• Advanced maternal age.• History of cholestasis with COC.• Multiple pregnancies.

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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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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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DIFFERENTIALS

1. Pruritis gravidarum2. Choledocholithiasis3. Preeclampsia4. Dermatoses

1. Pemphigoid gestationis2. Pruritic urticarial papules and plaques of pregnancy3. Atopic eruption of pregnancy 4. Pustular psoriasis of pregnancy

5. Viral hepatitis6. Acute fatty liver of pregnancy

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DIFFERENTIALS

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DIFFERENTIALS

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DIFFERENTIALS

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DIFFERENTIALS

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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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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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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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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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• 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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• 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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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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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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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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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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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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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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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?15/62/16352#H1

6. Kenyon AP. Obstetric cholestasis. RCOG Green-top Guideline No. 43.

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http://uptodate19.3/contents/mobipreview.htm?15/62/16352#H1

http://uptodate19.3/contents/mobipreview.htm?15/62/16352#H1

13. intrahepatic cholestasis of pregnancy3rd jun 15

Health & Medicine