# Chemoprevention of HCC related to MAFLD

> **NIH NIH P01** · BAYLOR COLLEGE OF MEDICINE · 2022 · $212,172

## Abstract

Metabolic (dysfunction) associated fatty liver disease (MAFLD) is now one of the most important risk factors for
hepatocellular cancer (HCC) in the U.S. Currently, no liver-specific therapies are approved for individuals with
MAFLD. Therapy that may block hepatocarcinogenesis – i.e., chemoprevention – is the only practical solution
to stem the rising tide of MAFLD-related HCC. In this context, three classes of medications (statins, metformin,
and glitazones) hold substantial promise because they act on different metabolic and/or stress-response
pathways important in MAFLD-related hepatocarcinogenesis, are commonly used to treat metabolic disorders,
and widely available. To our knowledge, no study has examined HCC chemoprevention in MAFLD. There is
also limited information about potential harms of these drugs, especially liver related adverse events (AEs)
which may be common in persons with MAFLD. The benefits and harms of chemoprevention are likely different
in different subgroups. Our study will evaluate the benefits and harms of HCC chemoprevention with these
three promising therapies in individuals with MAFLD. To do so, we will use, expand and extend a
previously assembled, well-characterized national cohort of MAFLD patients with extensive longitudinal clinical,
pharmacy, and laboratory data linked to detailed information from cancer registry, death registry and clinician
notes. Using this cohort, and as part of preliminary work, we showed a strong association between MAFLD and
HCC and reported an additive effect of metabolic traits on HCC risk. For Aim 1 (benefits of
chemoprevention), we will perform a series of carefully designed studies to evaluate the chemopreventive
effects of statins (vs. no statins), metformin (vs. no metformin) and pioglitazone (vs. no pioglitazone) in
reducing risk of incident HCC. We will also assess the heterogeneity of chemopreventive effects, with specific
focus on MAFLD patients with and without cirrhosis, those with varying severity of co-existing metabolic traits,
and perform dose-duration analyses to guide tailored chemoprevention. For Aim 2 (harms of
chemoprevention), we will use innovations in machine learning followed by manual review of medical charts
to conduct a comprehensive comparative evaluation of potential drug-related AEs among patients included in
Aim 1 emulated trials. Studies show that genetic factors contribute to differences in response to cancer
chemoprevention. In Aim 3 (genetic determinants of benefits), we will use data from an ongoing prospective
cohort of patients with MAFLD-cirrhosis to examine few suspected genetic markers that may modify the
chemopreventive effects of metformin and/or statins in individuals with MAFLD-cirrhosis. Our research is
significant because it will inform guidelines about who, when and how to recommend chemoprevention in
patients with MAFLD. Besides elucidating a potential chemopreventive effect in the general MAFLD population,
our emphasis on personalized che...

## Key facts

- **NIH application ID:** 10410751
- **Project number:** 1P01CA263025-01A1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** FASIHA KANWAL
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $212,172
- **Award type:** 1
- **Project period:** 2022-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10410751

## Citation

> US National Institutes of Health, RePORTER application 10410751, Chemoprevention of HCC related to MAFLD (1P01CA263025-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10410751. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*