Investigations

Investigations

• most specific laboratory test for intrahepatic cholestasis of pregnancy is measurement of plasma or serum concentration of total bile acids, which will usually include cholic or chenodeoxycholic acid: values may be 10 to 100 times those found in healthy pregnant women
• increases in serum transaminases are also common
• unlike in other cholestatic diseases, increases in serum gamma glutamyl transferase (GGT) are less common (1)
• if there is clinical uncertainty about the diagnosis of ICP, particularly with asymptomatic clinical presentation, then other investigations should be considered
• upper abdominal ultrasound can be performed to exclude gallbladder disease, duct dilatation and other liver pathology
• histological confirmation of acinar cholestasis and bile plugs is unnecessary except in atypical cases when symptoms start before 20 weeks, jaundice precedes pruritus, and itching persists after delivery
• other causes of pruritus and jaundice require exclusion, especially gall stones, primary biliary cirrhosis, sclerosing cholangitis, viral hepatitis, autoimmune chronic active hepatitis, and drug hepatotoxicity
  • serology for hepatitis A, B, C, Epstein Barr virus (EBV) and cytomegalovirus (CMV) can help to exclude viral pathology, while an autoimmune screen including anti-smooth muscle, liver-kidney microsomal (LKM) and antimitochondrial antibodies can help to identify women with chronic active hepatitis or primary biliary cholangitis

Notes

• in clinical practice, otherwise unexplained abnormalities in transaminases, gamma-glutamyl transferase and/or bile salts are considered sufficient to support the diagnosis of obstetric cholestasis
• the increase in alkaline phosphatase in pregnancy is usually placental in origin and so does not normally reflect liver disease
• bilirubin is raised only infrequently and most women will have increased levels of one or more of the remaining LFTs
• for defining abnormality in LFTs and bile salts, the upper limit of pregnancy-specific ranges should be applied
  • for transaminases, gamma-glutamyl transferase and bilirubin, the upper limit of normal throughout pregnancy is 20% lower than the non-pregnant range
  • bile acid levels can rise significantly after a meal, so while fasting might give lower values and help the diagnosis to be avoided in a few women with otherwise normal LFT, in the majority of studies and in clinical practice random levels are generally used
  • some women will have pruritus for days or weeks before the development of abnormal liver function: in those with persistent unexplained pruritus and normal biochemistry, LFTs should be measured every 1–2 weeks
  • isolated elevation of bile salts may occur but this is uncommon; normal levels of bile salts do not exclude the diagnosis

Reference:

1. Walker KF et al. Pharmacological interventions for treating intrahepatic cholestasis of pregnancy. Cochrane Database of Systematic Reviews 2020, Issue 7. Art. No.: CD000493. DOI: 10.1002/14651858.CD000493.pub3.
2. Royal College of Obstetricians and Gynaecologists. Intrahepatic cholestasis of pregnancy (Green-top Guideline No. 43). Published August 2022