# Early Detection of HCC Among Veterans With Liver Cirrhosis

> **NIH VA I01** · SOUTHEAST LOUISIANA VETERANS HEALTH CARE · 2022 · —

## Abstract

Hepatocellular carcinoma (HCC) is a primary malignant cancer of the liver that most often develops in the
background of liver cirrhosis (1,2). Hepatitis C virus (HCV) infection remains the major cause of liver cirrhosis
and HCC among US Veterans (3,4). Recent advances in antiviral treatment have allowed an increasing number
of cirrhotic patients to be cured with interferon (IFN)-free direct-acting antivirals (DAAs) (5,6). In the coming
years, hepatitis C eradication is expected to decrease, but not eliminate, the risk of HCC among cirrhotic patients
(7,8). The risk of HCC remains elevated post HCV clearance among patients with advanced fibrosis or cirrhosis
and is also magnified by other risk factors such as daily alcohol intake, obesity, metabolic syndrome, diabetes,
and race (African Americans or Hispanic) (7-16). HCC detected at an early stage can be effectively treated with
transplantation, resection or even loco-regional therapies, but HCC detected at a late stage has a poor prognosis.
The current HCC surveillance methods include liver ultrasound every six months with option of serum AFP
(AASLD guideline). However, these methods lack the specificity and sensitivity needed to detect HCC at an early
stage. Therefore, the development of a noninvasive, serum-based biomarker will allow early HCC detection and
effective therapeutic intervention. This multicenter grant application proposes to test the performance of liver-
specific serum biomarkers, together with standard-of-care tests including liver ultrasound, alpha-fetoprotein
(AFP) AFP-L3 and DCP for HCC detection to monitor HCC risk among cirrhotic patients. This validation study
will be performed by enrolling 2000 cirrhotic VA patients (HCV and non-HCV) from six different VA medical
centers. Based on the incidence rate of HCC among the cirrhotic population, we anticipate >50 HCC cases will
be detected at an early stage. Our hypothesis is that liver cirrhosis patients who do not resolve the ER-stress
response will remain at an increased risk of HCC and therefore continue secreting HCC-specific exosomes that
are enriched in glypican-3 and HSC70 (heat shock cognate protein 70) into the blood. Since the stress response
depletes miRNA-122 transcription, we postulate that measurement of serum miRNA-122 levels will provide a
powerful organ-specific biomarker for early prediction of cirrhosis regression after HCV cure. This application will
explore the performance of HCC-specific exosome biomarkers, miRNA-122 and their additional benefit to serum
AFP testing and liver ultrasound to improve surveillance of HCC and early detection of HCC. This hypothesis
will be tested using the following Specific Aims: Aim 1 will determine the performance of serum exosomal cargoes
(glypican-3, HSC70 and CD63) along with liver ultrasound, AFP, AFP-L3, DCP as a combined biomarker platform
for the early detection of HCC among Veterans with liver cirrhosis after HCV cure using a longitudinal multicenter
study. Aim 2 will...

## Key facts

- **NIH application ID:** 10477284
- **Project number:** 5I01BX004516-04
- **Recipient organization:** SOUTHEAST LOUISIANA VETERANS HEALTH CARE
- **Principal Investigator:** Srikanta Dash
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10477284

## Citation

> US National Institutes of Health, RePORTER application 10477284, Early Detection of HCC Among Veterans With Liver Cirrhosis (5I01BX004516-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10477284. Licensed CC0.

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