5 Questions About NAFLD and Intrahepatic Cholestatis of Pregnancy

Findings from a recent study show that intrahepatic cholestatis of pregnancy (ICP) may have more far-reaching implications than previously believed, which may change the way you manage ICP.

According to the study findings, pregnant women with ICP are 5.7 times more likely to receive a nonalcoholic fatty liver disease (NAFLD) diagnosis than their counterparts without ICP.¹

Gastroenterology Consultant reached out to two of the study’s authors, Erica Monrose, MD, and Tatyana Kushner, MD, to gain more insight about their team’s research.

GASTRO CON: What prompted you to conduct the study?

Tatyana Kushner: NAFLD is increasing in prevalence worldwide—especially in the United States—and it is now a leading cause of liver transplantation for women in the United States. ICP has long been associated with chronic liver conditions. Our original interest in this topic was that we have increasing prevalence of fatty liver disease, and we are looking to see whether there are any parallel increases in prevalence of ICP. We thought to look at this connection because of the role of bile acids in both NAFLD and ICP. Patients with fatty liver disease are known to have elevated bile acid levels. In ICP, the bile acid levels are elevated among pregnant women, which can have dangerous consequences for the fetus. We know that ICP in pregnancy is associated with other chronic liver conditions, such as hepatitis C virus infection, and we were looking to see whether there was any new association that we could find with fatty liver disease. To do that, we looked at the association between ICP and fatty liver disease, as well as the association between ICP and the metabolic risk for fatty liver disease.

GASTRO CON: Do you receive any common questions about your study or its results?

TK: One of the most common questions we have received is how we established a diagnosis of ICP. Oftentimes, women come in for a visit late during pregnancy, which is a dangerous condition for the baby, because they are normally delivered at this time. So, sometimes ICP is not officially diagnosed by the provider because it is such a rushed process. We have had questions about whether we had to go back and reclassify certain women as having ICP in pregnancy. And our answer to that is yes, sometimes we have had to do that. If the bile acid levels are elevated but the patients did not receive an official diagnosis of ICP, then we would mark them as having ICP in pregnancy, especially if it was written in the notes by the provider that there was a high suspicion for ICP.

Erica Monrose: Another question that has been asked is whether the women share risk factors for fatty liver disease and ICP, and that connection of NAFLD with ICP is a result of underlying metabolic risk (rather than association with NAFLD itself). We had a high number of Hispanic women in the ICP cohort, and it is known that Hispanic women have a high prevalence of certain genes that predispose them to fatty liver disease. Additionally, the hospital where we conducted the study had a large Hispanic patient population in general, and there was no difference in the prevalence of Hispanic patients in the ICP group vs control group. The patients’ body mass indexes (BMI) were very similar, so we did not have more women with obesity in the ICP cohort, which would lead to higher rates of fatty liver disease. The median BMIs in both groups were very similar. Thus, although metabolic risks were similar between groups, there was still a higher risk of ICP with NAFLD compared with those without NAFLD.

GASTRO CON: What is the main takeaway from your study?

EM: The major takeaway is for people to start thinking about ICP not just as a unique condition in pregnancy that does not have other implications, but that there may be associations with chronic liver disease, specifically fatty liver disease. It is important to know that fatty liver disease should not be dismissed during pregnancy, because that can have significant implications on pregnancy outcomes.

GASTRO CON: How do you hope this study impacts clinical practice?

EM: Patients with ICP rarely see a liver specialist. Also, there are no guidelines for follow-up of these women after pregnancy. Clinically speaking, most of the time, we see them during pregnancy, the baby is delivered, and then we never see them again. So, there is a need to evaluate the patients for underlying liver disease—especially if they have elevated liver test results in association with ICP—to make sure they do not have a chronic liver disease. We should also remember that it is not uncommon for obstetricians to perform ultrasonography of the abdomen for one reason or another during pregnancy; if they see steatosis on the ultrasonogram, I think the study findings reinforce the idea that this should raise their suspicion for the possibility of ICP development later on. They should have a lower threshold to check liver tests velocity in these women, evaluate them for liver disease, and counsel women. If patients develop classic symptoms of ICP such as pruritus, the health care provider should counsel their patients ahead of time and let them know they need to report when other symptoms arise so that the health care provider can diagnose ICP and prevent negative pregnancy outcomes.

GASTRO CON: How important is a multidisciplinary approach in ICP management?

EM: At Mount Sinai, we recently started a women’s liver clinic where a liver specialist sees women in the Department of Obstetrics and Gynecology who have liver-related issues, including ICP. I think this is a very important type of model, because if all the providers are right there, you can work in a much more interdisciplinary way to diagnose liver disease and link women to care for their underlying chronic liver disease after pregnancy.

Reference:

1. Monrose E, Ramirez Zamudio A, Aristide A, et al. Intrahepatic cholestasis of pregnancy (ICP) is associated with higher prevalence of NAFLD: a case-control study. Gastroenterology. 2019;156(6 suppl 1):S-1235–S-1236. doi:10.1016/S0016-5085(19)40085-1.