Cholestasis of pregnancy: Clinical sciences

Intrahepatic cholestasis of pregnancy, or ICP, is a rare pregnancy-specific liver disease that is characterized by pruritus and elevated serum bile acid levels. Typically, it presents in the third trimester with itching on the palms of the hands and soles of the feet, without a rash. It is a relatively uncommon disease but is associated with poor fetal outcomes, including preterm delivery, meconium-stained amniotic fluid, and stillbirth, due to an accumulation of bile acids in the fetus, as well as the amniotic fluid.

Let’s talk about the first steps to assessing a patient… When assessing patients who present with a chief concern suggesting ICP, start with a focused history and physical exam as well as labs, including total bile acids and liver transaminases, such as ALT and AST.

The hallmark symptom of ICP is pruritus, most often on the palms of the hands and soles of the feet which is worse at night. In general, symptoms start in the third trimester with the majority of cases diagnosed after 30 weeks gestation.

Risk factors include a personal or family history of ICP or preexisting hepatobiliary diseases, such as hepatitis C, nonalcoholic cirrhosis, and nonalcoholic pancreatitis, as well as gallstones and cholecystitis. ICP is also associated with advanced maternal age, multiple gestations, and in vitro fertilization.

On physical exam, there should be no rash present. If you visualize a rash, consider an alternative diagnosis, such as a dermatoses of pregnancy like atopic eruption of pregnancy, polymorphic eruption of pregnancy, or pemphigoid gestationis. That being said, you may note excoriations, since the pruritus can be quite intense.

When it comes to labs, the key finding in ICP is total bile acids greater than 10. Your patient’s liver transaminases may also be elevated. If the total bile acids are greater than 10 along with pruritus of the palms and soles without a rash, you can make the diagnosis of ICP. Also be sure to rule out other conditions that are associated with pruritus without a rash, such as chronic renal failure, liver disease, drugs such as opioids, and multiple sclerosis.

Here are a few clinical pearls about bile acids! When possible, check total bile acids in a fasting state, as there might be a small difference in levels between fasting and random blood work. However, if this is not a possibility, random bile acids will do just fine, as the difference is usually clinically insignificant and not likely to change clinical management. Additionally, if your patient’s total bile acids are initially normal and symptoms persist, repeat testing as indicated. This is because itching can actually precede an elevation in bile acids by several weeks! Finally, total bile acid levels can be repeated after making the diagnosis, as an elevation >100 will change management! This is because the higher the bile acids, the greater the risk for fetal complications.

Before we move on, here are some high-yield facts! Patients with bile acids greater than 40 are at an increased risk of developing preeclampsia. Preeclampsia typically develops a few weeks after the diagnosis of ICP, so it's important to discuss signs and symptoms to look out for with your patient. Also, if your patient’s initial screening for HCV was negative but is diagnosed with ICP, you should screen them again after this diagnosis.