EASL guidelines offer ‘framework’ for intrahepatic cholestasis of pregnancy care

Nina Rodriguez (Icahn School of Medicine at Mount Sinai, New York) presented the findings of a study looking at the distribution, clinical features, and outcomes associated with the ICP groups at the EASL Congress 2025 in Amsterdam, the Netherlands.

The team reviewed data for 121,830 women having a first pregnancy at a US health system between June 2009 and September 2024. Of these, 4386 (3.6%) had suspected ICP. After excluding 147 women with multi-fetal pregnancies and 139 who did not have liver tests, the researchers identified 4100 women with a singleton pregnancy and suspected ICP, based on pruritus with or without rash, or other indicators, and who underwent total serum bile acid (TSBA) and liver transaminase (LT) testing.

Using the EASL guidelines, 2648 (65%) patients were classified as Group A, with normal levels of TSBA and LTs, 998 (24%) were classified as Group B with normal TSBA but elevated LTs, and 454 (11%) were put into Group C based on having elevated TSBA with normal or elevated LTs.

In all, 11% of women had a TSBA greater than 19 μmol/L, 22% had a TSBA level above 10 μmol/L, and 34% had elevated LTs.

Rodriguez told delegates that, compared with 117,444 pregnant women from the general population without signs or symptoms of ICP identified over the same timeframe, suspected ICP patients were more likely to be older than 35 years, and have Hispanic ethnicity and government health insurance.

Moreover, the suspected ICP cohort were more likely to have both pre-existing comorbidities, such as hypertension and diabetes, and pre-existing liver disease, including viral hepatitis, primary biliary or sclerosing cholangitis, and non-alcoholic cirrhosis. Women with suspected ICP were also more likely than the general population to receive a postpartum hepatobiliary disease diagnosis, such as cholestasis.

In addition, suspected ICP was significantly linked to multi-fetal gestation, gestational diabetes, gestational hypertension, pre-eclampsia, and requirement for Cesarean delivery, although ICP was not significantly associated with an Apgar score below 7 points or fetal death.

Further analysis confirmed that the three risk groups had “distinct demographic and clinical profiles,” said Rodriguez.

In particular, Group B and C patients were significantly more likely than Group A patients to have Hispanic ethnicity (27.2 and 34.1 vs 19.8%, respectively), hepatitis C virus (1.2 and 2.2 vs 0.4%), and immune-mediated liver disease (0.8 and 2.9 vs 0.3%) or metabolic dysfunction-associated steatotic liver disease or metabolic dysfunction-associated steatohepatitis (MASLD/MASH; 2.6 and 1.5 vs 0.4%).

There was also a significantly higher rate of gestational diabetes in Group B and C than group A (14 and 12 vs 10%, respectively), and gestational hypertension (9 and 8 vs 5%).

In addition, Group C patients had significantly higher median TSBA than Groups A and B (26.9 vs 3.2 and 5.1 μmol/L, respectively), were significantly more likely to have a TSBA above 10 μmol /L (100 vs 5.6 and 23.1%), had significantly higher median alanine transaminase (80 vs 15 and 48 IU/L) and aspartate transaminase (61 vs 20 and 40 IU/L), and were significantly more likely to receive ursodiol therapy (67.8 vs 9.7 and 25.1%).

Women in Group C also had significantly higher rates of iatrogenic and spontaneous preterm birth than women in the other two groups, while infants born to Group C women had a significantly younger median gestational age at delivery and a higher rate of fetal respiratory distress syndrome.

In multivariate analysis, Group C risk stratification, gestational diabetes, autoimmune disease, and chronic hypertension were each associated with a 2.0–2.8-fold increased risk for spontaneous preterm birth, Rodriguez said.

Of note, women with a severe TSBA elevation above 100 μmol/L and those with a mild elevation of 20–39 μmol/L were 7.35 and 2.72 times more likely to experience spontaneous preterm birth, respectively, compared with patients with a very low TSBA below 10 μmol/L.

Group C patients were a significant 7.5 and 5.6 times more likely to have meconium-stained fluid than Group A and B patients, respectively, and a significant 4.6 and 1.7 times more likely to have an infant with fetal respiratory distress syndrome.

Finally, Group C patients were significantly more likely than Group A and B patients to have postpartum diagnoses of cholecystitis (3.3 vs 0.7 and 1.3%, respectively) and a new diagnosis of liver disease within 12 years of delivery (5.1 vs 1.8 and 3.2%), including MASLD/MASH, immune-mediated liver disease, and liver transplant, biliary or liver cancer, or cirrhosis.

Rodriguez summarized that patients who meet the Group B or Group C stratification criteria “warrant surveillance” and that elevated LTs alone can help risk stratification of ICP when TSBA testing is unavailable.

She added that Hispanic ethnicity and pre-existing liver disease could be used as part of targeted screening for ICP, while the high rate of post-partum liver disease detected in the study “underscores the value of long-term follow-up in patients with suspected ICP.”

The presenter concluded that the next steps in research include a plan to “integrate genetic findings with clinical phenotypes to refine stratification” and “identify variants associated with extreme TSBA elevation.”