How is ICP diagnosed?
Note: the information on this page has been updated following the publication of the third edition of the RCOG Green-Top Guideline on 9 August 2022.
Why have we changed the term ‘liver function test’ (LFT) to ‘liver blood test’?
Until recently, doctors have tended to call the blood test that looks at how well your liver is working a ‘liver function test’. The test checks to see if there is any inflammation or damage to your liver by looking for abnormalities in liver enzymes, such as:
- alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) – looks for inflammation
- bilirubin – to see if you’ve become jaundiced (where the whites of your eyes (sclera) can become yellow)
- gamma-glutamyl transferase (GGT) and alkaline phosphatase – can indicate damage/scarring to your liver. NB: in pregnancy, alkaline phosphatase rises without causing any problems to your liver. It can also remain elevated if you are breastfeeding, but this doesn’t mean you have to stop breastfeeding.
However, the phrase ‘liver function’ is misleading because although the enzymes mentioned above may be abnormal (in general liver disease as well as in intrahepatic cholestasis of pregnancy (ICP)), the liver is still doing the job it needs to do – in other words, it still ‘functions’. In ICP the bile flow may be slower than usual (meaning there is cholestasis, indicated by raised bile acid concentrations), but it is still doing everything it needs to do to keep you alive.
If doctors were worried about liver failure they would perform additional tests to check for this but liver failure is not associated with ICP, which is why you are unlikely to need them.
We think that using the term ‘liver blood test’ is not only more accurate, but will hopefully be less anxiety-provoking, and we anticipate that it will start to be used more frequently over the coming years.
There is no routine screening for ICP. It is not hard to understand why. One of the challenges is that the condition can present as early as 8 weeks and as late as 40 weeks. This means that women would need repeated screening throughout pregnancy. Also, as it is a relatively uncommon condition of pregnancy (affecting around 5,500 women a year in the UK), the cost implications of testing the whole pregnant population are obvious.
Instead, it is more likely that you will need to mention the itch, either at your antenatal appointment or by phoning the maternity day assessment unit/maternity helpline, and then tests will be performed.
- To make the diagnosis of ICP, other liver conditions and causes of itching may need to be ruled out first. These other conditions may include viral hepatitis, autoimmune hepatitis, and primary biliary cholangitis. It is a good idea to have a liver ultrasound scan in the pregnancy to confirm that nothing else might be causing your symptoms and abnormal blood test results, but the presence of gallstones does not exclude a diagnosis of ICP – it is possible to have both ICP and gallstones. Research shows that women with ICP have a higher chance of either already having had gallstones or of developing them in later life.
- Your doctor will need to ask you about your symptoms and may ask whether anyone else in your family has had liver problems during pregnancy.
- Research and anecdotal (personal reporting) evidence has shown that some women may itch for several weeks before their blood tests show any abnormalities. It is therefore important that you continue to have these tests if your bile acids are normal but you continue to itch.
Blood tests required:
Bile acid test – bile acids are chemicals produced in the liver to help with digestion. In ICP the flow of bile acids in the liver is reduced and they build up in the blood. A bile acid test is the most specific test for ICP and most experts in ICP will not confirm a diagnosis of ICP unless this is raised.
Bile acids have their own circadian rhythm, which means that they naturally rise and fall (within normal reference ranges) over a 24-hour period. The time of day at which you have your blood taken to measure your bile acids can make a small difference to your result, and any increase (within normal reference ranges) doesn’t mean that your bile acids are going to become abnormal or are rising – it could simply be that you have had them tested at a time of day when they are generally a little higher.
The latest research from Mitchell et al. (2021) shows that it is possible to miss the diagnosis of ICP if you fast for your bile acid test. This research also shows that the best time to have your test is around 30–120 minutes after you have eaten. There is no special food to eat – just eat what you would normally have for breakfast or lunch. Given what we have written it may also make sense to be consistent about the time of day you have your test and what you have eaten beforehand. There has been no research about this, but by doing this you will know that your results have not been affected by testing at different times or by eating different food.(Tap image to enlarge)(Click image to enlarge)
Not all hospitals perform the test and some hospitals have to send the blood sample elsewhere for testing. Ideally, you should be able to have the results within 48 hours, but we know that this is not possible for all women at the moment. It’s worth asking your health professional to chase your results if you know that they sometimes take longer to come back.
Bile acids are associated with stillbirth in ICP. Because of this risk, most women with ICP have been giving birth to their babies early. Induction has typically been recommended at around 37–38 weeks of pregnancy, but Ovadia et al. (2019) showed that around 90 per cent of women will be able to delay induction until 39 weeks of pregnancy. However, some women with severe ICP (greater than 100 µmol/L) may need to meet their babies from 34–35 weeks of pregnancy onward. It is essential that bile acids are tested frequently in ICP to ensure that women whose levels may rise above 100 µmol/L are identified, and that the results of these tests are received quickly. The majority of bile acids in this research were non-fasting samples, meaning that the level of risk was based on peak bile acid levels – another reason for not fasting for your bile acid test.
Liver blood test (also referred to as a liver function test – LFT) – this blood test looks at how well the liver is working by measuring the levels of different enzymes. The good news is that there is no association between stillbirth and raised liver enzymes in ICP alone. One or more of the following enzymes may be measured in a liver blood test – AST (aspartate aminotransferase), ALT (alanine aminotransferase), alkaline phosphatase or GGT (gamma-glutamyl transpeptidase). The AST and ALT levels are the ones that are used to support the diagnosis of ICP. Research has shown that aminotransferases sometimes rise before the bile acids. In 20% of women who develop ICP, the AST/ALT levels will be normal (Conti-Ramsden et al., 2019). As noted above, experts will not diagnose ICP until the bile acids rise.
(Tap image to enlarge)(Click image to enlarge)
Reference ranges for blood tests. The table below gives the normal values to be expected in both non-pregnant women and pregnant women without ICP.
The values may vary between laboratories – for example, some laboratories cite bile acids as low as <8.3 µmol/L as being abnormal, while others define abnormal as >14 µmol/L. This may be because of the different methods used to test the bile acids (liquid chromatography–mass spectrometry compared to enzymatic testing) or it may be that reference ranges could differ depending on the population involved – the lower range we have quoted seems to be pertinent to the Latina population.
The most recent research (Mitchell et al.) demonstrated that the bile acid threshold for diagnosing ICP should actually be ≥19 µmol/L. This new threshold will take time to filter through to hospitals testing for ICP.(Tap image to enlarge)(Click image to enlarge)
Source: Walker I, Chappell LC, Williamson C. Abnormal liver function tests in pregnancy. BMJ 2013;347:f6055 (https://doi.org/10.1136/bmj.f6055)