SAN DIEGO -- Pregnant women with non-alcoholic fatty liver disease (NAFLD) were at markedly increased risk for , in which bile acids accumulate in circulation and cause intense itching, researchers said here.
In a retrospective, single-center study of more than 300 women, those with NAFLD or steatosis on liver imaging were more likely to develop ICP compared to a control group of women with no evidence of fatty liver (odds ratio 5.7, 95% CI 2.09-15.65), reported Erica Monrose, MD, and Tatyana Kushner, MD, both of the Icahn School of Medicine at Mount Sinai in New York City.
Compared to the control group, those with NAFLD were also more likely to develop ICP if they had biliary disease prior to pregnancy (OR 3.29, 95% CI 1.39-7.80) or alanine transaminase levels more than twice the upper limit of normal (50 U/L), they reported at Digestive Disease Week.
"We know that in fatty liver disease, one of the things that is increased in women is bile acid levels and we also know that for cholestasis of pregnancy, bile acids are increased," Monrose told ѻý. "It's been associated with other chronic liver conditions like hepatitis C and gallstones ... so we thought that if there was an increasing prevalence in fatty liver disease, then there might be a parallel increase in ICP."
Bile acids have been shown to be that regulate certain metabolic pathways in NAFLD. This evidence, paired with the fact that women with ICP have increased rates of metabolic risk factors, suggests "there is reason to suspect some overlap in NAFLD and ICP," said Heather Patton, MD, of Kaiser Permanente, who was not involved with this study.
"This study is an important first step in evaluating a potential relationship between these conditions," Patton told ѻý in an email.
However, few women had liver ultrasound data in this study, and the results presented here need to be confirmed with other measures of hepatic steatosis across the board, she said.
"Potential implications of further investigations may include better defined at-risk populations for ICP that may guide perinatal screening and care, therapeutic targets for both conditions, and improved linkage to postpartum care for women with NAFLD," she said.
Kenneth Sherman, MD, PhD, of the University of Cincinnati, agreed that because this was a retrospective analysis, researchers were limited in their ability to obtain bile acid levels for the control group of women. It thus remains possible that controls also had evidence of ICP consistent with fatty liver, which could confound the results.
He also noted that Hispanic women are more susceptible to ICP in pregnancy, gallstones, and fatty liver disease, and were overrepresented in this study (upwards of 60%). Taking account of these covariates would be important in discerning what's driving the study results.
Although there may be an association that persists overall, "prospective evaluation of matched samples where all patients receive liver imaging ... and bile acid measurement would be an interesting and useful step forward in this research area," Sherman told ѻý.
For the study, Monrose, Kushner, and colleagues collected data from women who delivered at Elmhurst Hospital Center in New York City in 2017. The 149 women in the case group had a confirmed diagnosis of ICP and the 200 women in the control group did not have bile acid level test orders, a marker that they had no indication of ICP, researchers said.
Women in both groups were a mean age of 30 and both had an average body mass index of about 27 kg/m2. Other metabolic risk factors including cholesterol, rates of hypertensive disorder, and pre-gestational/gestational diabetes were not significantly different across groups.
Because there were no significant differences in metabolic risk factors for fatty liver disease detected between women with ICP and the control group, this could indicate a direct link between NAFLD and ICP, the authors noted.
"I think the field of fatty liver disease is growing rapidly and becoming an important topic to study in terms of biomarkers, identifying the people who are at risk, and conditions that are associated with fatty liver disease," Kushner said. "Given its rising in prevalence and that 30% of the western world has some evidence of fatty liver disease, to know that those patients may be at higher risk of developing ICP would really inform our practices because ICP can potentially have very negative outcomes for the pregnancy."
Disclosures
Monrose was supported by the TL1 Mentored Clinical Research Training Program and Kushner was supported by the American Association for the Study of Liver Diseases (AASLD) Clinical, Translational, and Outcomes Research Award.
No other relevant disclosures were reported.
Primary Source
Digestive Disease Week
Monrose E, et al "Intrahepatic cholestasis of pregnancy (ICP) is associated with higher prevalence of NAFLD: a case-control study" DDW 2019; Abstract 1562.