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Understanding Intrahepatic Cholestasis of Pregnancy

Diagnosis/definition: Intrahepatic cholestasis should be suspected when pruritis develops in the absence of a rash.  Lab evidence of cholestasis includes elevated bile acids (> 10 umol/L).  Up to 60% of patients will have elevated transaminases and 20% of patients will have increased direct bilirubin levels.
Epidemiology/Incidence: 0.3-0.5% among the general population with up to 15% incidence in Latin American countries.  Incidence also increased in Hepatitis C infection (6-16%).
Risk factors/associations: Multiple gestation, chronic hepatitis C, prior history or family history of intrahepatic cholestasis.
Complications: Associated with an increased risk of preterm delivery, meconium passage, intrapartum fetal heart rate abnormalities, and fetal death (IUFD incidence most often less than 5% in reports).
Prevention: There are no preventative therapies or interventions available.

  • Preconception counseling:  Risk of recurrence is between 50-60% in subsequent pregnancies after an affected index pregnancy.  In cases of family history for intrahepatic cholestasis, there may be up to a 92% rate of incidence in planned pregnancy.  A genetic etiology may underlie these recurrence statistics.
  • Screening/Work-up:  Pruritis should lack a rash in intrahepatic cholestasis.  The evaluation of bile acids is confirmatory for cholestasis of pregnancy.  Bile acids should exceed 10 umoL/L.  Evaluation of transaminases and direct bilirubin should also be completed as these are increased in 20-60% of cases.  Screening for hepatitis C should also be considered in risk groups since cholestasis incidence is higher among these patients.
  • Prenatal care:  Upon diagnosis of intrahepatic cholestasis, prenatal intervention for treatment of symptoms of cholestasis is indicated.  Ursodeoxycholic acid (UDCA) has been most effective for treatment of pruritis.  The starting dose of UDCA is 300 mg twice daily and can be increased to 600 mg twice daily when pruritis persists after a week of therapy.  UDCA also decreases bile acids and transaminase levels though this has not been demonstrated to improve fetal outcomes.  S-Adenosylmethionine can be used with UDCA for a synergistic reduction in bile acid and transaminase levels. Antihistimines, corticosteroids, or cholestyramine can be used for pruritis but are not superior to UDCA.  
  • Antepartum testing:    Antepartum fetal monitoring is recommended in the antenatal management of intrahepatic cholestasis.  However, the type, duration, or frequency of testing has not been identified.  The mechanisms of fetal death are not understood.  Most fetal demises occur late in gestation and may occur in the presence of previously reassuring fetal testing.  There are no evidence based recommendations for fetal testing in intrahepatic cholestasis.
  • Delivery: While an evidence based recommendation is not available for the timing of delivery when cholestasis of pregnancy is encountered, most management strategies would advocate delivery between 37-38 weeks or sooner with documented pulmonary maturity.  Prior obstetrical history, antenatal testing, and gestational age should be considered.    

Post-partum/breastfeeding:  Resolution of pruritis usually occurs within days of delivery.  Hormonal contraception and/or breastfeeding are not contraindicated in pregnancy complicated by cholestasis.