# HCV and co-morbid alcohol use disorders: a translational investigation of antiviral therapy outcomes on CNS function

> **NIH VA I01** · PORTLAND VA MEDICAL CENTER · 2020 · —

## Abstract

Chronic hepatitis C virus (HCV) infection is often associated with extrahepatic manifestations, including
central nervous system (CNS) damage and neuropsychiatric impairments that can be exacerbated by
alcohol abuse. More than half of patients with chronic HCV infection complain of “brain fog” (impaired
cognition, fatigue). The introduction of direct-acting antiviral (DAA) therapies has revolutionized HCV
treatment, with sustained viral response (SVR) rates of ~90%. The VA is now offering DAA therapy to all
Veterans with HCV treated within VA health care systems, including those with alcohol use disorders
(AUDs)—a common co-morbidity among Veterans with HCV. Despite this progress and expansion in
HCV treatment efforts, there are insufficient data on brain function outcomes (e.g., outcomes that affect
daily life such as cognitive abilities, fatigue, and substance abuse behavior) following DAA therapy.
There are also limited data on the effects of viral clearance on inflammatory factors that putatively
influence neuropsychiatric function. This Merit Review project plans to conduct a longitudinal study of
adults (with and without AUDs) undergoing antiviral therapy for the treatment of HCV. Demographically-
matched comparison groups of Veterans without HCV (with and without AUD) will also be evaluated to
determine the relative contribution of HCV to outcomes that are affected by alcohol abuse. It is
hypothesized that adults with HCV and co-morbid AUDs may be at increased risk of persistent brain
dysfunction following DAA therapy. By comparing neuropsychiatric functioning, cortical activity, white
matter integrity, and immune response among Veterans with and without active AUD before and after
DAA therapy, results from this study are expected to determine the extent of improvement in brain
function (e.g., neural connectivity and cognitive abilities) and reduction in inflammation that is achieved
by successful completion of DAA therapy. Two specific aims are proposed. Aim 1 will evaluate the
impact of DAA therapy on CNS function in Veterans with HCV and will test the hypotheses that following
DAA therapy and obtaining an SVR, participants will show: i) improved neuropsychiatric outcomes (e.g.,
cognitive function, fatigue, mood), as compared to baseline (pre-DAA therapy), ii) restored functional
connectivity and disintegrity within white matter tracks that had detectable deficits at baseline, and iii)
normalization of immune activation profiles (e.g., decreased expression of inflammatory cytokines and
restored T cell phenotypes), as compared to baseline. Aim 2 will use general linear models to assess
whether change in the response (e.g., CNS functional outcomes) between post- and pre-DAA therapy
differs among the four groups—either due to AUD, HCV, or the potential interaction of these factors—to
determine the impact of an active AUD on neuropsychiatric, neuroimaging, and immunological outcomes.
Participants will be assessed at baseline and 12 weeks pos...

## Key facts

- **NIH application ID:** 9815311
- **Project number:** 5I01BX002061-06
- **Recipient organization:** PORTLAND VA MEDICAL CENTER
- **Principal Investigator:** JENNIFER M LOFTIS
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2013-10-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9815311

## Citation

> US National Institutes of Health, RePORTER application 9815311, HCV and co-morbid alcohol use disorders: a translational investigation of antiviral therapy outcomes on CNS function (5I01BX002061-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9815311. Licensed CC0.

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