| Intrahepatic Cholestasis of Pregnancy | |
|---|---|
| Classification and external resources | |
| ICD-10 | O26.6 |
| ICD-9 | 646.73 |
| DiseasesDB | 6884 |
Intrahepatic cholestasis of pregnancy (also known as "cholestasis of pregnancy,"[1] "jaundice of pregnancy,"[1] "obstetric cholestasis,"[1] and "prurigo gravidarum"[1]) in the United Kingdom, is a medical condition in which cholestasis occurs during pregnancy. It typically presents with troublesome itching[2] and can lead to complications for both mother and fetus.
Itching has long been considered to be a common symptom of pregnancy. The vast majority of times, itching, or pruritus, is a minor annoyance caused by changes to the skin, especially that of the abdomen. However, there are instances when itching is a symptom of ICP. This is usually most intense on the palms of the hands, and the soles of the feet, but can be wide spread.
ICP occurs most commonly in the third trimester, but can begin at any time during the pregnancy. It is also the second most common cause of jaundice in pregnancy.
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Maternal consequences include the following:
Fetal consequences include:
Delivery has been recommended in the 38th week when lung maturity has been established. [3]
Most women with this condition present in third trimester with intense itching without a rash. Generally, the itching is localized to the abdomen, legs, palms, and soles, but can be generalized.
Hallmarks of ICP include the following symptoms:
Most common:
Less common:
It is important to note that not all ICP sufferers have all of the above symptoms. For example, Jaundice only occurs in relatively small subset of cases, and in some cases abnormal lab results were not seen until 15 weeks or more after the onset of symptoms.
The causes of intrahepatic cholestasis of pregnancy are still not fully understood.[3] Hormones and genetic factors are likely to be important in the pathogenesis of the disease.[4] A number of features of the disease suggest a link to hormones:[5]
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.[7]
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 also has a role in ICP.[4]
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.[4] Genetic mutations in the hepatocellular transport protein ABCB4 (MDR3), which controls secretion of phosphatidylcholine into bile, have been found in 15% of cases of ICP.[8]
Genetic mutations affecting hepatic bile salt transport molecules have also been found in patients with progressive familial intrahepatic cholestasis (PFIC). It has been found that mothers of patients with PFIC have a higher incidence of ICP, suggesting that heterozygote carriers of these mutations are also predisposed to ICP.[4]
In addition to genetic changes to bile salt transport molecules, high levels of estrogen glucuronides have been shown to inhibit the bile salt export pump (BSEP) ABCB11,[9] and high levels of progesterone to inhibit the ABCB4 (MDR3) phospholipid transporter.[10]
Consequently, both genetic mutations in hepatocyte proteins involved in bile secretion together with inhibition of those proteins by high levels of hormone metabolites in pregnancy may have roles in the pathogenesis of ICP.[3]
A number of features of ICP suggest that environmental factors also have a role in the disease:
While most pregnant women experience some itch from time to time, itching on the palms and soles without a visible rash, or persisting severe or extensive itch symptoms should be reported to the midwife or obstetrican.
To obtain a diagnosis of ICP, there are two LFT and Serum bile acid test. The liver function tests (LFTs) is a simple blood test, the results of which should be available by the next day. If the ALT level is elevated, this, plus pruritus of palms and soles, should be treated as diagnostic of ICP (however LFT's are not always elevated in ICP patients). The serum bile acid blood test for ICP is a quantitative measurement of bile salts. The results of this test often take longer to return, but the test is more specific for ICP.
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 and certain medications, should also be considered.
Upon diagnosis, most providers will prescribe Ursodeoxycholic Acid. While there is no cure for ICP, and no way to guarantee a successful outcome, studies have shown a slightly better fetal and maternal outcome from administration of Ursodeoxycholic Acid, whereas Cholestyramine appears to only relieve itching.[7]
If additional blood tests to check clotting function identify a problem, giving Vitamin K may help avoid the risk of hemorrhage at delivery.
Delivery by 37 completed weeks is considered crucial to fetal outcome [12], though it does not completely eliminate the risks associated with the condition.
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