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Study finds link between intrahepatic cholestasis of pregnancy and risk of NAFLD



Patients with intrahepatic cholestasis of pregnancy (ICP) were nearly six times more likely to have a diagnosis of nonalcoholic fatty liver disease (NAFLD) than were controls, results from a retrospective, single-center study demonstrated.

Dr. Tatyana Kushner, assistant professor of medicine in the division of liver diseases at the Icahn School of Medicine at Mount Sinai, New York.

Dr. Tatyana Kushner

“If this connection is confirmed with future studies, intrahepatic cholestasis of pregnancy may prove a novel model through which to investigate bile acid metabolism in patients with fatty liver disease,” one of the study authors, Tatyana Kushner, MD, MSCE, said during a media briefing in advance of the annual Digestive Disease Week. “This could have implications for future management of fatty liver disease. Additionally, these findings suggest that ICP patients should be seen by a liver specialist because they may go on to develop chronic liver disease or may already have already existing underlying liver disease.”

ICP is characterized by a build-up of bile acids during pregnancy and is associated with an increased risk of negative fetal outcomes and fetal death if left untreated, said Dr. Kushner, of the division of liver diseases at the Icahn School of Medicine at Mount Sinai, New York. The most notable symptom during pregnancy is severe pruritus. In what is believed to be the first study of its kind, Dr. Kushner and colleagues set out to evaluate the association between ICP and NAFLD and associated metabolic risk factors, including obesity, dyslipidemia, hypertension, and diabetes. Between January and December of 2017, they drew from the electronic medical records of a New York City health system to identify 149 pregnancies complicated by ICP and compared them to a control group of 200 pregnancies without an ICP diagnosis. The researchers used Pearson’s chi-square or Fisher’s exact test and Wilcoxon rank-sum tests to evaluate association of ICP with categorical variables and continuous variables, respectively, and unadjusted odds ratios to compare the ICP and control groups for clinically significant outcomes.

The median age of the study population was 30 years, their mean body mass index was 27.5 kg/m2, and there was a higher proportion of Hispanic women in the ICP group, compared with the control group (75% vs. 62%, respectively). Dr. Kushner and colleagues found that Hispanic women were nearly twice as likely to be diagnosed with ICP than non-Hispanic women (OR, 1.90; 95% confidence interval, 1.87-3.03). However, patients in both the ICP and control groups were similar for median age (OR, 1.02; 95% CI, 0.99-1.06), nulliparity (OR, 0.79; 95% CI, 0.48-1.30), and prevalence of hepatitis C (OR, 1.35; 95% CI, 0.08-21.67). The two groups were also similar for certain metabolic risk factors, including prevalence of obesity (OR, 1.01; 95% CI, 0.62-1.61), hypertension (OR, 0.69; 95% CI, 0.31-1.52), hemoglobin A1c greater than 5.5% (OR, 0.80; 95% CI, 0.34-1.9), and total cholesterol above 200 mg/dL (OR, 4.15; 95% CI, 0.83-20.84). Median bile acid levels were 30.6 micromoles (interquartile range, 11.6, 32.7) in the ICP group.

Compared with patients in the control group, those in the ICP group had higher median levels of alanine aminotransferase (ALT) (32 vs. 16 U/L; P less than .0001), alkaline phosphatase (181 vs. 128 U/L; P less than .0001), and total bilirubin (0.5 vs. 0.35 mg/dL; P less than .0001). ICP patients were also more likely than their counterparts to have ALT levels above 50 U/L (two times the upper limit of normal; OR, 3.22; 95% CI, 1.48-7.03), a history of biliary disease (OR, 3.29; 95% CI, 1.39-7.80), and to have evidence of steatosis on liver imaging (OR, 4.69; 95% CI, 1.68-13.12). When the researchers evaluated a diagnosis of NAFLD based on ICD-10 codes or evidence of steatosis on liver imaging, ICP patients were significantly more likely to have a diagnosis of NAFLD than controls (OR, 5.7; 95% CI, 2.08-15.65).

“We recommend additional research to look at differences in NAFLD progression in women who had NAFLD and were later diagnosed with ICP, compared to women with NAFLD who did not go on to develop ICP, because that may be a reflection of the role that bile acid metabolism plays in these particular patients,” Dr. Kushner said.

Digestive Disease Week is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).

The study’s primary author was Erica Monrose, MD. The researchers reported having no financial disclosures.

SOURCE: Monrose E et al. DDW 2019, Abstract Sa1562.

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