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Pregnancy in primary sclerosing cholangitis (PSC) is not well studied. There is little known regarding how pregnancy might affect PSC, and how the disease might affect the fetus. In general, advice regarding conception for a woman with PSC reflects knowledge gleaned from a few small studies and case reports 1–5 A common question for a newly diagnosed patient with PSC pertains to future fertility and childbearing. The case series published in this issue of Gut by Wellge and colleagues6 (see page 1117) provides an important look at pregnancy in PSC. In the review by Wellge et al, 229 patients with PSC were evaluated as were 569 healthy controls. The authors found that the number of children was not different between the two groups. This would imply that fertility was not affected by the diagnosis of PSC. A total of 17 patients with known PSC and at least one pregnancy, or diagnosed with PSC within 6 months of delivery, were included in this series. Twenty-five pregnancies in total were studied. Of these, elevated liver enzymes occurred in 20% during pregnancy and 32% post partum. No data was provided on the frequency of liver test abnormalities during pregnancy and post partum in the healthy controls.
Intrahepatic cholestasis of pregnancy (ICP) was suspected in two patients based on liver test elevations and an increase in pruritus. This would be higher than what would be typically expected. While the incidence varies throughout the world, on average up to 1% of pregnancies are affected by ICP.7 We suspect making this diagnosis would be particularly challenging as the presentation would be essentially indistinguishable from worsening PSC. There was, however, no evidence of biliary obstruction or stricture on ultrasound imaging, and two patients were so pruritic as to require pre-term delivery. In addition, the patients developed symptoms later in pregnancy. Intrahepatic cholestasis of pregnancy usually manifests during late pregnancy and disappears spontaneously after delivery.7 The improvement in pruritus after delivery in these two patients, if it indeed occurred, would help corroborate this diagnosis. The relatively high number of cases of ICP in this review suggests there may be novel pathways that warrant further study in regard to disease pathogenesis.
The paper by Wellge and colleagues has the benefit of being the largest series to date, as well as possessing the longest follow-up. Prior to this paper, a Swedish study of 13 pregnancies in 10 patients with PSC published in 19962 was the largest series. In this review, seven patients were identified as diagnosed with PSC before pregnancy while two developed the disease during pregnancy. One patient was diagnosed within 2 months of delivery.
In this group, two patients had unexplained pruritus and two had right upper quadrant pain prior to pregnancy, and these symptoms continued throughout the pregnancies. Abdominal pain developed in three patients lacking this symptom before pregnancy. Four patients without pruritus prior to pregnancy developed this symptom during the pregnancy and ursodeoxycholic acid (UDCA) was used in none. In two patients, pruritus was so intense as to bring on premature delivery. Liver tests did not indicate any deterioration during pregnancy and no fetal losses occurred. The authors in this study suggested that in patients with PSC, pregnancy does not seem to have a negative effect on the disease. Neither the mothers nor the babies demonstrated any ill effects.
Use of UDCA as treatment for PSC is controversial. There is data suggesting harmful effects when used at doses of 28–30 mg/kg/day.8 Yet in this study, patients who used UDCA during pregnancy more often experienced stable liver enzyme levels when compared with those who did not take UDCA (13% vs 67%, p=0.049). Eight patients in this review used UDCA after the first trimester and nine (stated as nine on page 12, stated as eight on page 14) patients took it throughout the entire pregnancy at a mean dose of 16 mg/kg/day.
With the study by Wellge and colleagues, and those published previously, we have the opportunity to provide patients with PSC information regarding the potential course of their disease if they indeed become pregnant. In general, pregnancy did not lead to negative outcomes for the patient with PSC or the fetus. Use of UDCA at a moderate dose may be indicated for those patients who have an increase in pruritus or worsened liver tests.
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