# Project 3: Non-invasive assessment of liver fibrosis stage and progression in obesity and diabetes: a Hispanic population study

> **NIH NIH P50** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2021 · $671,469

## Abstract

PROJECT 3 – SUMMARY/ASTRACT
HCC incidence and mortality rates are rapidly increasing in the United States, in part due to the epidemics of
obesity and diabetes. The greatest increase has been seen in Hispanics in South Texas. Our studies in the
Cameron County Hispanic Cohort (CCHC) established from a community with high rates of obesity (52%) and
diabetes (28%), showed that chronic liver disease is also common (42%). Non-alcoholic fatty liver disease
(NAFLD), the most common liver manifestation of obesity and diabetes, ranges from simple steatosis to non-
alcoholic steatohepatitis (NASH). Advanced fibrosis is the main risk factor for HCC in NAFLD patients. We first
reported a 3.5% prevalence of advanced fibrosis in CCHC, with a remarkable population attributable fraction of
65% for central obesity. We then implemented liver fibrosis screening in CCHC, using vibration-controlled
transient elastography (VCTE), and reported a 14% prevalence of clinically significant fibrosis (stage ≥F2). The
prevalence of significant liver fibrosis reached 28% in obese and diabetic subjects. Strong associations
between gut microbiota changes and progression of NAFLD to NASH and HCC, have been reported and bile
acids are important mediators in this gut-liver cross-talk. Furthermore, we identified fatty acids as non-invasive
markers of NAFLD activitiy and liver fibrosis in patients with NAFLD. Our long-term translational goal is to
determine the contributing factors and molecular drivers of liver fibrosis in obese and diabetic Hispanics in
South Texas, the community in the United States with the highest rate of HCC, and identify those at risk of
progression to advanced fibrosis and therefore HCC, so preventive interventions can be implemented. We
hypothesize that demographic, clinical, and molecular (microbiome features, bile acids, fatty acids)
parameters are associated with liver fibrosis stages in obese Hispanics with diabetes. We hypothesize further
that a model based on these parameters will predict fast fibrosis progression and thus increased risk for HCC
development in these subjects. We will enroll 900 obese and diabetic CCHC subjects and 500 obese and
diabetic Hispanic patients scheduled for liver biopsy at participating liver clinics. All study participants will be
screened for liver fibrosis with VCTE and plasma bile acids, plasma fatty acids and gut microbiome features
will be measured. Study participants identified with fibrosis ≥F2 will be followed prospectively and liver fibrosis
will be again assessed by VCTE and/or liver biopsy at 36 months. In Aim 1, we will determine the performance
of VCTE against liver fibrosis for fibrosis staging in the study population. We will also determine the prevalence
and risk factors associated with liver fibrosis in obese and diabetic Hispanics in South Texas. In Aim 2, we will
identify the molecular markers among those measured that are associated with liver fibrosis stages. In Aim 3,
we will identify a model incorpora...

## Key facts

- **NIH application ID:** 10246499
- **Project number:** 5P50CA217674-03
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** LAURA BERETTA
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $671,469
- **Award type:** 5
- **Project period:** 2019-09-25 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246499

## Citation

> US National Institutes of Health, RePORTER application 10246499, Project 3: Non-invasive assessment of liver fibrosis stage and progression in obesity and diabetes: a Hispanic population study (5P50CA217674-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10246499. Licensed CC0.

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