Mechanism
The causes of intrahepatic cholestasis of pregnancy are still not fully understood, but are thought to be caused through a combination of genetics, hormones and environment. Hormones, environmental and genetic factors are all thought to contribute to the condition. ICP commonly occurs in the third trimester at the time when hormone levels are at their highest. Twin and triplet pregnancies, which are associated with higher hormone levels, show a higher incidence of ICP. ICP resolves quickly after delivery, when placental hormone production ceases. Older high-dose estrogen oral contraceptive pills could cause features of ICP. Estrogens
Estrogens, and particularly glucuronides such as estradiol-17β-D-glucuronide, have been shown to cause cholestasis in animal studies, by reducing bile acid uptake by hepatocytes. Progesterone
Treatment with progesterone in the third trimester of pregnancy has been shown to be associated with the development of ICP, and levels of metabolites of progesterone, particularly sulfated progesterone, are higher in patients with ICP than unaffected women, suggesting that progesterone may have a bigger role than estrogen in ICP. Genetic factors
Clustering of cases of ICP in families, geographic variation in rates of ICP, and recurrence of ICP in 45-70% of subsequent pregnancies all suggest a genetic component to the disease. Genetic mutations in the hepatocellular transport protein ABCB4 (MDR3), which controls secretion of phosphatidylcholine into bile, have been found in cases of ICP.Genetic mutations affecting hepatic bile salt transport molecules have also been found in patients with progressive familial intrahepatic cholestasis.
It is important to note that as the level of itch does not correlate with bile acid levels (shown to be the most likely cause of stillbirth in ICP), the itch in ICP can range from being mild to severe.To obtain a diagnosis of ICP, a liver function test and a serum bile acid test should be requested. Although the ALT level may be raised, 20% of women with ICP will always have a normal LFT test result. This, plus pruritus of palms and soles, could be considered as potentially diagnostic of ICP but only with elevated bile acid levels (however LFTs are not always elevated in ICP patients). The serum bile acid blood test for ICP is a quantitative measurement of bile acids. Other problems with the liver that occur in pregnancy should be considered by the treating clinician. These include preeclampsia, the HELLP syndrome, and acute fatty liver of pregnancy. Furthermore, other causes of hepatitis, like hepatitis viruses, cancer and certain medications, should also be considered. Treatment
Many providers will prescribe ursodeoxycholic acid. The most recent trial, PITCHES, did not show an overall beneficial effect, but some researchers believe that it may still be useful to offer ursodeoxycholic acid to women whose bile acids are > 40 μmol/litre.