# Epigallocatechin gallate for prevention of lethal cirrhosis complications

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $585,642

## Abstract

Summary
Hepatocellular carcinoma (HCC) is the leading cause of death in patients with cirrhosis, and the fastest rising
cancer mortality in the U.S. Due to the limited efficacy of existing therapies for established HCC tumors,
prognosis for patients remains poor, with five-year survival under 15%. Thus, HCC chemoprevention in cirrhosis
is likely the most impactful strategy to improve survival. However, despite the candidate chemopreventive agents
suggested in experimental studies, it remains an unmet need due to logistical difficulty in conducting clinical trials
that require large sample size and long follow-up time. To overcome the challenge, we identified Prognostic Liver
Secretome signature (PLSec) to quantitatively monitor therapeutic modulation of HCC risk level in cirrhosis
patients, and predict reduction of future incident HCC. PLSec has been used as a surrogate endpoint in our
ongoing and planned HCC chemoprevention clinical trials. Experimental studies in rodent models by us and
others suggested that epigallocatechin gallate (EGCG), a green tea catechin, prevents HCC development
without any adverse events. Our ex vivo organotypic culture of precision-cut liver slice (PCLS) from cirrhosis
patients revealed suppression of high-risk signature by EGCG, supporting its clinical relevance. Based on these
promising findings, the goal of our proposal is to test our hypothesis that EGCG treatment safely suppresses
PLSec in patients with cirrhosis. Aim 1. Evaluate safety and efficacy of EGCG in cirrhosis patients (phase II
double-blinded placebo-controlled clinical trial). We will evaluate 24-week EGCG treatment or placebo in 60
patients (1:1 randomization) with early-stage cirrhosis enriched for elevated HCC risk by a clinical variable-based
score (FIB-4 index) and PLSec. Participants will be monitored monthly for adverse events. Serum samples will
be obtained before, during, and at the end of treatment. Primary endpoint: reduction of risk level as measured
by PLSec (delta-PLSec). Secondary endpoints: safety profile, change in quality of life. Exploratory endpoints:
change in on-treatment PLSec, immunohistochemistry of HCC-risk-related markers for participants consented
for liver biopsy, and incident HCC. Aim 2. Identify factors associated with response to EGCG in cirrhosis patients.
We will evaluate pre-treatment PLSec and clinico-histological variables; on-treatment PLSec modulation and
plasma concentration of EGCG and its metabolites for their association with the primary endpoint. We will also
assess modulation of the FIB-4 index and liver stiffness measurement by acoustic elastography as potential
alternative clinical endpoints to monitor effect of EGCG, We expect to establish novel HCC chemoprevention
with a dietary supplement for subsequent pivotal phase III clinical trial toward clinical translation of this approach,
which will contribute to a transformative improvement in the outcome of patients with HCC by enabling individual-
risk-base...

## Key facts

- **NIH application ID:** 10922759
- **Project number:** 5R01CA282178-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Yujin Hoshida
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $585,642
- **Award type:** 5
- **Project period:** 2023-09-06 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10922759

## Citation

> US National Institutes of Health, RePORTER application 10922759, Epigallocatechin gallate for prevention of lethal cirrhosis complications (5R01CA282178-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10922759. Licensed CC0.

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