The Influence of Cholestatic Liver Disease on Pregnancy Outcomes Is Understudied

Real-world findings from a large national cohort, presented at The Liver Meeting 2025, in Washington, D.C., showed that clinicians could benefit from targeted recommendations that can better guide the management and counseling of women with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) during pregnancy. 

When rare, chronic liver diseases such as PBC and PSC develop during pregnancy, it may be hard to distinguish between their clinical manifestations and those associated with intrahepatic cholestasis of pregnancy (ICP), a condition related to hormonal changes that typically resolves after delivery. An increase in alkaline phosphatase levels is detected in women with ICP, but is also a typical characteristic of chronic cholestatic liver diseases. While the American Association for the Study of Liver Diseases provides some guidance on the monitoring of liver function and the continuation of ursodeoxycholic acid (UDCA) in pregnant women with PBC, there is a lack of consensus-based recommendations for the management of cholestatic liver diseases in pregnancy due to limited data. Providers who treat women with PBC or PSC before and during their pregnancies rely on information from retrospective studies to guide clinical decision-making and to counsel patients living with these conditions. 

“Understanding of these diseases in pregnancy is limited, with counseling often extrapolated from risk related to intrahepatic cholestasis of pregnancy,” said presenting author Priyanka Gaur, MD, a fellow in the division of maternal-fetal medicine at Weill Cornell Medicine, in New York. “It is difficult to study these conditions in pregnancy for a [few] reasons: they are rare, there is a male predominance of PSC, and there is a late average age of PBC diagnosis in women.”  

Gaur and colleagues conducted a retrospective analysis of data from the TriNetX research network, available from 106 hospitals in the United States, to evaluate the independent effects of PBC and PSC on pregnancy outcomes. The analysis included 447 women with PBC and 282 with PSC, who had confirmed singleton pregnancies between 2005 and 2025. After propensity score matching to exclude confounding factors, the outcomes of women in each group were compared to those of an equal number of pregnant women without cholestatic liver disease. The investigators looked at the influence of PBC and PSC on adverse outcomes, which included preterm delivery, preeclampsia, ICP, gestational diabetes, postpartum hemorrhage, Cesarean section, and fetal growth restriction. 

As expected, the prevalence of both chronic cholestatic liver diseases was rare, with PBC affecting one in nearly 11,000 pregnant women and PSC documented in one in approximately 17,000 pregnant women. Overall, pregnant women with PBC and PSC had similar risk profiles compared with their counterparts without chronic liver disease, however, the risk of developing intrahepatic cholestasis of pregnancy was significantly elevated in women with PSC. The results showed an 11% absolute risk of developing ICP in women with PSC, which was significantly higher than the 3% risk in matched pregnant women in the control group. Across the cohort, women who developed ICP had much higher odds of preterm birth than those without ICP, regardless of chronic liver disease status. The authors observed that the risk of developing ICP may be underestimated in this population, as some of the data were collected before the introduction of the ICD-10 code for this condition in 2023. 

“To our knowledge, this is one of the first studies reporting [cholestatic liver] disease prevalence in the pregnant population,” Gaur said. “Women with a diagnosis of ICP and elevated bile acids had a higher risk of preterm birth, and it is likely that the current practices of additional fetal surveillance and treating elevated bile acids are appropriate and should be encouraged.” Approximately half of the women with PBC and of those with PSC were being treated with UDCA, according to their health records. Continuation of UDCA during pregnancy, which is routinely recommended for women with PBC, could also benefit pregnant women with PSC. 

“The results are drawn from a diverse, real-world population with demographics representative of the United States,” Gaur added. “This is one of the largest studies exploring contemporary pregnant populations with PSC and PBC, [with the findings] adding to obstetricians’ and gynecologists’ understanding of rare, understudied cholestatic conditions. Our findings begin to inform prenatal counseling and serve as a basis for predictive modeling informing future management guidelines.” 

Gaur and collaborators are planning to analyze global data to better understand the mitigating effects of UDCA on bile acid elevation and on key obstetric outcomes, as well as liver disease progression in this population.