Approach

ICP should be diagnosed in pregnant women with pruritus and raised serum bile acid concentrations in the absence of other causes, such as pre-existing liver disease.[14][76] Affected women often have associated liver dysfunction; most have elevated liver transaminase levels and a small proportion have raised bilirubin levels.[10] Itch often commences prior to elevations of serum biochemistry, hence repeated testing should be performed in women who remain symptomatic.[6][9] Internationally, the limited availability of rapid bile acid testing has led to hypercholanaemia (raised serum bile acid concentrations) not always being used for diagnosis. However, the clear association of adverse perinatal outcomes with bile acid concentrations, and not with other markers of liver dysfunction, highlights the importance of this test for diagnosis of ICP.[2] Indeed, up to 20% of women with ICP do not have elevated liver transaminase levels.[10]

History

Although the maternal itch of ICP is classically described to occur on the palms of the hands and soles of the feet, pruritus can occur at any site, including all over the body.[6] Typically, the itch is most severe at night, and this can result in severe sleep disturbance.[8] Women often report associated fatigue. Right upper quadrant abdominal pain is not infrequent and this may be associated with underlying cholelithiasis.[16] Women commonly report dark urine and may have pale stools.[11] Although the majority of women have symptoms beginning in the late second and third trimesters, ICP has been reported from early in the first trimester; early-onset persistent disease is likely to be more severe.[3][4][77]

The past medical history may include previous occurrence of ICP, pruritus with hormonal contraceptives or following antibiotic or proton pump inhibitor exposure, cyclical (menstrual) pruritus, and other liver or biliary conditions (particularly hepatitis C or gallstones).[6][41][78]​ Similarly, women may report a family history of ICP.[31] 

Physical examination

Excoriations are common, and can develop secondary infection, but no other rash is indicative of the condition.[5] Around 10% of women have jaundice, evident by yellow sclerae.[5][10][12] Women may have some right upper quadrant tenderness on examination, but ICP is not otherwise associated with clinical abnormalities on abdominal examination. ICP is not associated with abnormalities on obstetric examination - there is not an established association with growth restriction of the fetus.

Given that the condition is associated with increased rates of gestational diabetes mellitus and pre-eclampsia, physical examination should also consider features of these associated conditions, such as accelerated fetal growth, polyhydramnios, glucosuria, proteinuria, hypertension, hyperreflexia, epigastric pain, and peripheral oedema.

Laboratory

As pruritus occurs in more than 20% of pregnant women, diagnosis is dependent on elevation of serum bile acid concentrations, commonly with associated liver dysfunction. The following tests are recommended:[10][14][76][79][80]

  • Total serum bile acid concentrations: above the upper limit of the laboratory normal range

  • Alanine aminotransferase: raised above pregnancy-specific concentrations in around 80% of women with ICP

  • Bilirubin: raised above pregnancy-specific concentrations in around 10% of women with ICP

  • Alternative liver enzymes, such as aspartate aminotransferase and gamma-glutamyl transferase, can also be elevated in ICP.

If bilirubin elevation is marked or persistent, consider investigations to identify the cause.[79]

Alternative diagnostic laboratory tests have not been found to be superior to the measurement of total bile acid concentrations, or are not routinely available.[54][81] These include measurement of individual bile acid concentrations and the enzyme autotaxin levels or activity. Diagnostic liver biopsy is not recommended.

Additional testing should be selected on the basis of the patient history and risk factors present, for example:

  • Auto-antibody tests: such as anti-smooth muscle and anti-mitochondrial antibodies for chronic active hepatitis and primary biliary cholangitis

  • Virology testing: hepatitis C, Epstein-Barr virus (in women with a history of preceding infectious symptoms), and cytomegalovirus

  • Coagulation testing: women with steatorrhoea or evidence of marked liver synthetic impairment (e.g., low albumin) are at risk of coagulopathy, although this is not evident in the whole population of women with ICP, and thus routine testing is not recommended[82]

  • Full blood count: to exclude anaemia as an alternative cause for pruritus.[83]

Laboratory tests to rule out alternative diagnoses can be considered, according to history and examination findings (e.g., ultrasound is commonly performed to exclude co-existent liver and biliary tree pathology). It is important to ensure that maternal serum bile acid and liver transaminase concentrations return to normal by 3 months postnatally.[79]​ If a woman has ongoing abnormalities, further investigations should be performed to exclude co-existing hepatic pathology.

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