INTRAHEPATIC CHOLESTASIS OF PREGNANCY

doi:10.1016/S1089-3261(05)70050-7

Clinics in Liver Disease

Volume 3, Issue 1, 1 February 1999, Pages 1-13

https://doi.org/10.1016/S1089-3261(05)70050-7 Get rights and content

Intrahepatic cholestasis of pregnancy (ICP) is a well-defined liver disease that is unique to pregnancy. Signs of cholestasis, particularly pruritus, usually occur during the second or third trimester and, by definition, disappear spontaneously after delivery. ICP is a benign disease for the mother, but it carries a risk for the pregnancy because of the possibility of premature delivery and sudden fetal death. This risk for the baby requires the obstetric team and the hepatologists to be familiar with ICP, especially since active, timely obstetric intervention improves fetal prognosis.

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EPIDEMIOLOGY

ICP has been identified all over the world, but its prevalence varies greatly according to country and to ethnic origin (Table 1). ICP is more common in Scandinavian countries, Bolivia, and Chile. In Chile, the prevalence, which in 1974 and 1975 was evaluated at 15.6% (i.e., 11.8%–27.7% according to ethnic origin), recently has decreased to between 4% and 6.5% for unknown reasons.51, 58, 59

Generally, ICP is more frequent in twin pregnancies,²⁶ which is not surprising considering the role of

CLINICAL FINDINGS

As a rule, skin pruritus, which is the main symptom, appears in late pregnancy, although it can appear as early as the 10th week.¹⁰ The pruritus, which initially is localized, often becomes generalized, but predominates on the palms and the soles of the feet. Pruritus may engender considerable discomfort, and generally is more severe at night and disturbs sleep. Pruritus declines a few hours after delivery and usually disappears in the few days following delivery. Clinical examination of the

BIOLOGIC FINDINGS

Liver function tests are essential to confirm the diagnosis of cholestasis when a pregnant woman experiences pruritus. In such patients, an increase in serum transaminase activity or in serum bile acid concentration usually is enough to confirm the diagnosis of cholestasis.

Clinicians should bear in mind that serum transaminase activity remains within normal limits during normal pregnancy and that an increase should be taken into account whatever the level.⁴ Both aspartate transaminase (AST) and

ULTRASONOGRAPHY

Ultrasound examination of the liver in patients suffering from ICP reveals no dilatation of the intra- and extrahepatic bile ducts³⁶; however, fasting and ejection volumes of the gallbladder have been found to be greater in patients with ICP than in normal pregnant women.³⁶ Gallstones may be identified in the gallbladder. A significant association has been found between ICP and gallstone disease in Sweden and Chile.23, 25 In a case-control study, the frequency of gallstone disease was found to

PATHOLOGY

Liver biopsy rarely is necessary for the diagnosis of ICP. Histopathology is characterized by pure cholestasis, sometimes with bile plugs in hepatocytes and canaliculi and predominantly in zone 3. Inflammation and necrosis usually are not observed, and portal tracts are unaffected.⁶²

MATERNAL AND FETAL OUTCOME

Maternal prognosis is good, and ICP never leads to chronic liver disease. Cholestasis frequently recurs in subsequent pregnancies,33, 68 however the severity of the pruritus, the date of onset, and the intensity of the changes in liver function tests may differ in consecutive pregnancies.⁵⁵

The administration of oral contraceptives to women with a history of ICP rarely results in cholestasis,¹⁶ and ICP is not a contraindication for oral contraceptives.⁵ Oral estroprogestogen contraception with a

PATHOPHYSIOLOGY

The cause of ICP is unknown; however, the results of epidemiologic and clinical studies suggest genetic, hormonal, and exogenous factors (Fig. 1)

Genetic factors could explain familial cases and the higher incidence in some ethnic groups, such as the Araucanian Indians of Chile.⁵¹ Regarding the markers of genetic susceptibility of the human leukocyte antigen (HLA) system, no statistically significant association of ICP with HLA-A,-B, and -C antigens⁵⁴ or with HLA-DPB1 alleles have been

MEDICAL TREATMENT

Hydroxyzine (25–50 mg/d) may alleviate the discomfort of pruritus.

Cholestyramine (8–16 g/d) decreases ileal absorption of bile salts and increases their fecal excretion, but its effect on pruritus is limited.⁴¹ This treatment should be initiated progressively to improve the digestive tolerance.

The efficacy of S-adenosylmethionine is a matter of debate.21, 22, 58 In two Italian, placebo-controlled studies, intravenous administration of S-adenosylmethionine (800 mg/d) induced a significant

OBSTETRIC MANAGEMENT

The obstetric team has the responsibility of deciding whether early delivery is necessary. This decision may be influenced by several factors. The first is the number of weeks gestation because the risk of death in utero is increased during the last month of pregnancy. The second concerns the severity of the cholestasis, which can be evaluated by the serum bilirubin concentration and possibly by serum bile acid concentrations. It has been suggested that serum bile acid concentration levels

CONCLUSION

When a pregnant woman experiences pruritus, cholestasis can be diagnosed easily by serum liver function tests; however, the cholestasis may be caused by a disease other than ICP per se, (e.g., UTI or viral hepatitis). These diseases should be systematically ruled out, especially in countries where the prevalence of ICP is low or when there are atypical features, such as abdominal pains or fever. By contrast, with the lack of risk for the mother, ICP carries a risk for the baby because of the

ACKNOWLEDGMENTS

The author wishes to thank Mrs. Doreen Raine for reviewing the English text.

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