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    Prof. of Hepatology & Gastroenterology, Cairo University.

    Consultant of Hepatology,Gastroenterology and Endoscopy

    Management Positions: •

    Chief of Hepatology unit El Manial University Hospital (1994-1998).

    • Chief of Gastroentero ICU in Cairo university hospital (1997-2000)

    • President of the board of AlfaScope GI Specialized center (2004-2014).

    • Head of Endoscopy Unit in Cairo University Hospitals (2005-2010).       


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    استاذ الكبد و الجهاز الهضمى بكلية الطب جامعة القاهرة

    استشارى الكبد و الجهاز الهضمى و المناظير

    دكتوراه امراض الكبد و الجهاز الهضمى من كلية الطب جامعة القاهرة

    الرئيس السابق لقسم الامراض الباطنية بكلية الطب جامعة ٦ اكتوبر

    الرئيس السابق لوحدة مناظير الجهاز الهضمى و مركز الكبد و الرعاية المركزة بقصر العينى


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Thursday, Dec 12th

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Intrahepatic cholestasis of pregnancy

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Intrahepatic cholestasis of pregnancy (ICP)


In most studies ranges from 1.5-5.5%.


Unknown. Genetic, hormonal & environmental factors are likely involved .

1. Genetics:

There are familial cases and higher incidence in some ethnic groups.

2. Hormones:

Estrogens are known to cause cholestasis. ICP occurs mainly during the third trimester, when serum concentrations of estrogen reach their peak. ICP is also more common in twin pregnancies, which are associated with higher levels of circulating estrogens.

Administration of progesterone may be a risk factor for ICP. Progesterone treatment is recommended to be avoided in pregnant women with a previous history of ICP and immediately withdrawn when cholestasis occurs during pregnancy.

Whether in-vitro fertilization (IVF) affects

 the incidence or severity of ICP is unclear. While data are limited, it suggests that patients with a history of cholestasis related to estrogen exposure should be monitored carefully when undergoing ovarian stimulation, and if possible, mildly stimulated.

3. Environmental:

The seasonal variability that has been observed in some countries suggests that environmental factors could modulate the expression of the disease. However, no environmental factors except the treatment with natural progesterone during pregnancy.


Cholestasis, without inflammation. Bile plugs in hepatocytes and canaliculi predominate in zone 3.

Clinical picture:

Most women are diagnosed during the second or third trimester. The onset is typically indicated by the development of pruritus, which is often generalized but predominates on palms & soles, and is worse at night. Pruritus may precede laboratory abnormalities. Features of liver failure are unusual. Jaundice occurs in less than 10% of cases. The presence of jaundice without pruritus is rare.


Bilirubin: total & direct are elevated . Total bilirubin rarely exceed 6 mg/dL.

ALT & AST: are elevated, and may reach values greater than 1000 U/L, making distinction from viral hepatitis important.

GGT level is normal or slightly elevated, which is unusual in most other forms of cholestatic liver disease.

Alkaline phosphatase & 5 nucleotidase are elevated. However, alkaline phosphatase is not specific for cholestasis during pregnancy due to expression of the placental isoenzyme.

Serum total bile acid concentrations increase in ICP, and may be the only laboratory abnormality.

Ultrasonography: the liver looks normal.


I. For the mother:

The maternal prognosis in ICP is good. Pruritus usually disappears in the first few days following delivery, accompanied by normalization of liver tests. Affected women have no hepatic sequelae.

Cholestasis recurs during subsequent pregnancies in 60-70% of cases. Recurrent episodes are variable in severity.

The administration of estrogen-progestin oral contraceptives to women with a history of ICP rarely results in recurrent cholestasis. So, oral contraception with a low dose of estrogen can be initiated after normalization of liver function tests. However, women should be informed of the possible risks of pruritus or cholestasis.

ICP is not a contraindication to breastfeeding.

II. For the fetus:

ICP carries significant risk for the fetus.

The main complications are fetal prematurity, intrauterine fetal death, and neonatal respiratory distress syndrome.

1. Prematurity:

The incidence varies greatly among studies (6-60 %).

2. Intra-uterine fetal death:

Rarely occurs before the last month of pregnancy. The median gestational age at fetal death is 38 weeks.

There is no ideal method for fetal surveillance in ICP.

Serum total bile acid concentration has been suggested to predict fetal risk in ICP. In the largest study, which included 693 women with ICP, fetal complications were not observed until bile acid levels were ≥40 micromol/L. However, determination of bile acid concentrations may take several days, making it an impractical tool for immediate risk stratification.

Non-stress tests (NST) and other tests for detection of the effects of chronic placental insufficiency on the fetus may not be useful in ICP because the mechanism of intrauterine fetal demise is thought to be a sudden event rather than the result of a chronic placental vascular process. However, obstetricians use ante-partum testing in women with ICP to detect fetal compromise and the need for immediate delivery.


To reduce symptoms, and prevent maternal & fetal complications.

1. Ursodeoxycholic acid (UDCA):

Controlled trials demonstrated that UDCA improved pruritus and liver tests, and had no adverse effects in the mothers or babies. The optimal dose has not been determined yet, but the usual is 500 mg twice a day or 300 mg three times a day until delivery.

2. Other drugs:

  • Hydroxyzine: (25 to 50 mg/day) may improve pruritus, but can aggravate respiratory difficulties in preterm babies.
  • Cholestyramine: (8 to 16 g/day) should be initiated with a small dose and gradually increased. However, its effect on pruritus is limited and  was less effective than UDCA in a controlled trial.

•          Dexamethazone: in a recent controlled trial, did not improve pruritus or reduce the serum ALT, and was less effective than UDCA at reducing bilirubin and bile acids.

Timing of delivery:

The best approach is early delivery; the timing should be guided by the patient’s symptoms and the potential risks associated with prematurity.

No randomized trials have evaluated the optimum gestational age for delivery, and there is no consensus whether delivery should be at 37 or 38 weeks of gestation, or earlier.

Some obstetricians deliver patients with ICP at 37 weeks because the majority (90%) of intra-uterine fetal death occurs after 37 weeks (median 38 weeks), thus the risk of fetal death (1-3%) in ongoing pregnancies outweighs the morbidity associated with iatrogenic delivery at 37 weeks of gestation. However, early delivery will result in increased rates of cesarean delivery and admission to the neonatal intensive care unit.

Some authors advocate  performing amniocentesis at 37 weeks and delay delivery for one week if the results suggest pulmonary immaturity.

Indications for delivery prior to 37 weeks of gestation because of ICP include severe pruritus not relieved with pharmacotherapy, jaundice, or a prior history of intra-uterine fetal death due to ICP. The timing of delivery in these situations is empirical and generally as long as possible after 35 weeks of gestation.  All patients electively delivered for ICP prior to 37 weeks are extensively counseled, If the patient chooses to be delivered, amniocentesis is performed and deliver if the results are mature. If testing demonstrates pulmonary immaturity, administer a course of corticosteroids and proceed with labor induction upon completion.

Last Updated on Sunday, 18 November 2012 19:56


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