# Applying an 'omics' approach to predict hepatic decompensation events and hepatocellular carcinoma in veterans after HCV cure with direct acting antiviral therapy

> **NIH VA I01** · DURHAM VA MEDICAL CENTER · 2022 · —

## Abstract

The Department of Veterans Affairs is the single largest hepatitis C virus infection health care provider in the
United States. Since the introduction of direct acting antivirals for the treatment of HCV infection in 2014, VA has
cured over 100,000 Veterans. Due to the high rate of comorbidities in the veteran population, including HIV co-
infection, alcohol use, and obesity and metabolic syndrome, rates of severe liver fibrosis prior to DAA therapy
are high and likely to persist despite cure. While sustained virologic response (SVR), a virologic surrogate of
HCV cure, is associated with decreased risk of hepatic decompensation (i.e., ascites, spontaneous bacterial
peritonitis (SBP), hepatic encephalopathy (HE), esophageal variceal bleed), hepatocellular carcinoma (HCC),
and liver-related mortality, Veterans with severe liver fibrosis prior to cure remain at high risk for such events and
all-cause mortality. To date there are no reliable laboratory tests or biomarkers to differentiate patients with the
greatest risk of post-SVR decompensation events, HCC, and liver-related death. We have discovered a group
of lipid and lipid-related metabolites that accurately predict risk of liver-related complications in people with HIV
and HCV co-infection, approximately 2 years prior to the incident event. We propose to validate this biomarker
in a cohort of patients who have achieved HCV cure. Once validated, we propose to test the biomarker in a real-
world Veteran cohort to ensure generalizability. Successful validation of the metabolite profile will support
translational investigations to gain an understanding of the fundamental biology associated with the metabolites
and potential pathways for therapeutic targets of fibrosis and HCC. For Aim 1 we will validate a biosignature of
circulating lipid and lipid-related metabolites that is predictive of incident hepatic decompensation events and
HCC in patients with cirrhosis who achieve HCV cure with DAA therapy. We will conduct a nested case-control
study, leveraging a pre-existing cohort of patients with HCV and cirrhosis who achieved cure with DAA therapies
and are followed prospectively for liver-related complications. We will perform comprehensive targeted
metabolomic profiling to validate a prognostic metabolic profile. For Aim 2 we will develop integrated “clinico-
metabolic” models incorporating clinical variables and metabolite biomarkers that identify Veterans at greatest
risk of hepatic decompensation events and HCC after achieving HCV cure with DAA therapy. We will enroll
Veterans with severe liver disease into a prospective, observational study, conducted at two VA sites, after DAA-
induced HCV cure. Using a nested case-control design we will complete comprehensive targeted metabolite
profiling to develop optimized models to predict liver-related events. For Aim 3 we will use an integrated high-
dimensional biology approach of peripheral blood and liver tissue to optimize blood-based predictive mo...

## Key facts

- **NIH application ID:** 10260234
- **Project number:** 1I01CX002147-01A2
- **Recipient organization:** DURHAM VA MEDICAL CENTER
- **Principal Investigator:** Cynthia A Moylan
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2021-10-01 → 2025-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10260234

## Citation

> US National Institutes of Health, RePORTER application 10260234, Applying an 'omics' approach to predict hepatic decompensation events and hepatocellular carcinoma in veterans after HCV cure with direct acting antiviral therapy (1I01CX002147-01A2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10260234. Licensed CC0.

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