# Targeting Nonalcoholic Fatty Liver Disease during the reproductive period to improve women's health outcomes

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $707,389

## Abstract

Nonalcoholic fatty liver disease (NAFLD), and its progressive form, nonalcoholic steatohepatitis (NASH), is the
leading cause of cirrhosis and liver transplantation in women, yet it is often undiagnosed until overt
complications have developed. Non-invasive tests can now identify “at-risk” NASH, defined as having the
highest risk for liver disease progression. Women of reproductive age commonly engage with healthcare
systems during their pregnancy care, providing a unique opportunity to identify “at-risk” NASH early,
particularly because metabolic changes in pregnancy may initiate and/ or worsen NAFLD progression. As
such, we first conducted a multidisciplinary protocol to screen for NAFLD in pregnant individuals, Fatty Liver in
Pregnancy (FLIP) I, in which we identified 1) a 14% overall prevalence of NAFLD in pregnant individuals, 2)
Hispanic ethnicity and pre-pregnancy weight as key predictors of NAFLD in pregnancy, and 3) in a pilot study
of postpartum assessment, found that 83% of individuals had worsening NAFLD grade post-delivery. Given
that hepatic lipid metabolism dysregulation plays a central role in NAFLD initiation and progression, in a
preliminary lipidomics analysis in FLIP I participants, we identified distinct lipidomic profiles in individuals with
NAFLD in pregnancy (compared to non-pregnant individuals with NAFLD), and clustering of polyunsaturated
fatty acid-derived oxidized fatty acids in individuals with NAFLD, gestational hypertension and preeclampsia,
emphasizing the potential shared role of these lipid pathways in the pathogenesis of NAFLD and these
adverse pregnancy outcomes (APOs). With our findings from FLIP I, we are now poised to study the
longitudinal influence of NAFLD in pregnancy, and associated lipid parameters, on women's health. In the
proposed FLIP II study, we seek to evaluate the evolution of NAFLD in pregnancy and its influence on
pregnancy outcomes, identify predictors for the development of “at-risk” NASH after pregnancy, and evaluate
the NAFLD driven lipid based mechanisms that predict these events. We will prospectively screen 1540
pregnant individuals for NAFLD (by ultrasound and Fibroscan) in early pregnancy and enroll them for
longitudinal follow up for up to one year postpartum. We will administer detailed questionnaires collecting
sociodemographic, dietary, and clinical data and collect and bank serum specimens for analysis. Our specific
aims are 1) To determine the association between NAFLD in pregnancy and APOs; 2) To evaluate antepartum
factors that predispose to “at-risk” NASH post-pregnancy; and 3) To investigate the lipidomics-based
mechanisms underlying NAFLD in pregnancy and its association with post-delivery “at-risk” NASH. By
uncovering novel insights into the natural history of NAFLD/ NASH in women in the pregnancy/ postpartum
period, our study will help stratify risk factors for NASH progression and provide valuable information for future
targeted interventions in this subgroup. Ultimate...

## Key facts

- **NIH application ID:** 10858545
- **Project number:** 1R01DK139189-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Tatyana Kushner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $707,389
- **Award type:** 1
- **Project period:** 2024-08-15 → 2024-11-06

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10858545

## Citation

> US National Institutes of Health, RePORTER application 10858545, Targeting Nonalcoholic Fatty Liver Disease during the reproductive period to improve women's health outcomes (1R01DK139189-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10858545. Licensed CC0.

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