ReviewIntrahepatic cholestasis of pregnancy: molecular pathogenesis, diagnosis and management
Section snippets
Hormonal factors: estrogens
Genetic predisposition and hormonal factors play key roles in the pathogenesis of ICP. Evidence for a primary role of hormonal factors in ICP was provided by the following observations (2):
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The disease starts in the last trimester which is the period of the highest hormone concentrations.
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Twin pregnancies display both a higher incidence of ICP and more pronounced rises in hormone levels.
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ICP resolves promptly after delivery, when levels of placental hormones return to normal.
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In further
Symptoms
In the past, icterus was believed to be the major clinical finding in ICP. However, the most common symptom is severe pruritus, which most typically appears in the third trimester and starts in palms and soles. In 10% of the patients, pruritus develops in the first trimester and 25% of the patients present with pruritus in the second trimester (70). The pruritus is generally more severe at night and can lead to considerable discomfort for the patients. Only 10% of the patients with pruritus
Diagnosis
Liver function tests are to be performed in every pregnant woman who experiences pruritus. The increase of serum bile acids in combination with typical pruritus is highly suggestive of the diagnosis of ICP.
Among standard liver tests, alanine transaminase (ALT) is a very sensitive parameter for ICP (3). Serum transaminase levels are normal until delivery in healthy pregnancies and therefore, any rise should alert and lead to further tests. ALT is released into the blood in increasing amounts
Differential Diagnosis
The main differential diagnoses of pruritus of ICP without icterus are skin diseases, allergic reactions and pruritus related to abdominal striae. Only 0.07% of all pregnant woman develop visible icterus (95). The clinician distinguishes icterus in graviditate, the coincidence of icterus and pregnancy, from icterus e graviditate as a specific complication of pregnancy (Table 3). The acute fatty liver of pregnancy presents with transaminases up to 12 μkat/l (500 U/l), severe hypoglycemia,
Management
ICP is a fairly common disease with a high impact on fetal morbidity and mortality, and it is also a condition of great discomfort for the patients. Obstetric management of patients with ICP varies widely over the world. In spite of numerous reports of increased fetal risk 4., 5., 96. many obstetric clinics still choose to manage ICP pregnancies expectantly. Many different protocols for intensified surveillance have been proposed. It has been shown that a regimen including weekly fetal
Pharmacological Treatment
Antihistamines, anion exchange resins and phenobarbital are given to remove putative peripheral pruritogens or to reverse their effects on empiric grounds (97). These therapeutic options have not received wide acceptance for treatment of ICP patients because of their ambiguous efficacy or side effects. Anion exchange resins such as colestipol or colestyramine bind bile acids and interrupt their enterohepatic circulation. They should therefore be given separately from ursodeoxycholic acid (UDCA,
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