# Estimating the Contribution of Alcohol and Metabolic Risk to Liver Disease Progression to Inform Personalized Interventions

> **NIH NIH K23** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2022 · $192,888

## Abstract

PROJECT SUMMARY/ABSTRACT
Alcohol- (ALD) and non-alcoholic fatty (NAFLD) liver disease are the two leading etiologies of liver disease,
accounting for more than 50% of liver-related mortality, and both rapidly rising in incidence. ALD and NAFLD
are histologically indistinguishable, but clinically stratified by distinct alcohol thresholds—yet, alcohol use and
metabolic risk often co-exist in individuals. Despite the frequent intersection of these risks, the longitudinal
effects of alcohol use and metabolic risk over time on liver disease progression are understudied. An improved
understanding of these interactions, particularly among different individual profiles (i.e. age, sex, race), can
inform personalized algorithms for fibrosis assessment and surveillance, and individualized thresholds for
alcohol use interventions. Investigation of novel biomarkers (e.g. proprotein convertase subtilisin kexin type 9
[PCSK9]) may lead to precision-interventions to prevent and treat liver disease. To address these knowledge
gaps, we will leverage CARDIA (a large biracial cohort with 35 years of prospective alcohol and metabolic
data) amplified by serial Enhanced Liver Fibrosis (ELF) testing of previously banked serum samples. The
scientific aims are to: (i) identify trajectories and thresholds of alcohol use and obesity, associated with
presence and progression of liver fibrosis (Aim 1); (ii) develop sex- and race-specific models to identify
individuals at highest risk of liver disease, by demographic, metabolic, and alcohol profiles (Aim 1a); (iii) assess
the role of null PCSK9 alleles on liver fibrosis by demographic, metabolic, and alcohol profiles (Aim 2). The
training goals, which will be achieved through formal courses, workshops, didactics, hands-on experience and
structured mentorship, are to: (i) develop expertise in metabolic risks and inter-relatedness with alcohol; (ii)
learn advanced biostatistical methods in multi-level interactions and longitudinal analyses (e.g. trajectory and
JoinPoint); (iii) acquire knowledge in translational biomarkers and genetic epidemiology, focused on clinical
interventions. These scientific aims and training goals are made possible by a rich scientific environment at
University of Southern California, access to a unique prospective community-based cohort (CARDIA), and a
strong multidisciplinary mentorship team consisting of Dr. Terrault (chronic liver diseases, clinical and
translational studies, clinical trials expert), Dr. Mack (advanced biostatistics, genetic epidemiology, clinical trials
expert), and Dr. Leventhal (alcohol and addiction, longitudinal studies expert). All mentors have significant
experience with K to R-mentorship, and will ensure Dr. Lee’s achievement in milestones that will lead to his
position as a productive independent investigator. This research will set the stage for future NIH R-funded
studies focused on personalized approaches to the screening and prognostication within the ALD/NAFLD
intersec...

## Key facts

- **NIH application ID:** 10352120
- **Project number:** 1K23AA029752-01
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Brian Pei Lim Lee
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $192,888
- **Award type:** 1
- **Project period:** 2022-07-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10352120

## Citation

> US National Institutes of Health, RePORTER application 10352120, Estimating the Contribution of Alcohol and Metabolic Risk to Liver Disease Progression to Inform Personalized Interventions (1K23AA029752-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10352120. Licensed CC0.

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