# Sex hormones and HCV-related liver disease progression

> **NIH VA I01** · MICHAEL E DEBAKEY VA MEDICAL CENTER · 2021 · —

## Abstract

Over 260,000 male veterans accessing VA healthcare between 2000 and 2014 had a laboratory confirmed
diagnosis of hepatitis C virus (HCV) infection. Chronic HCV infection (HCV+) is the leading cause of liver
disease progression to cirrhosis, liver transplant and liver cancer. HCV+ males have much higher rates of liver
disease progression than HCV+ females. One factor that may contribute to this difference is large and gender-
defining biological differences in the levels of circulating sex hormones like testosterone. However, the role
normal variability in these major sex hormones plays in risk of liver disease progression among HCV+
individuals of the same gender is not known. The long-term effects of medications that substantially alter sex
hormone levels like testosterone therapy on risk of disease progression in HCV+ males are also unknown.
We previously recruited baseline cohort of 1072 male veterans with chronic HCV infection seen for routine care
at single VA. All completed a lifetime risk factor survey and had a blood sample taken to obtain DNA and to
store for biomarker testing in approved future research studies. We propose to measure circulating
levels of major sex hormones at baseline using stored blood samples for this cohort of 1,072
HCV+ male veterans. We will also perform DNA tests to assess specific variations in several genes related
to sex hormone function. We will prospectively follow all cohort members for liver disease progression with
outcomes determined using electronic medical record review and VA database searches and expert physician
consensus review. We will examine the association between baseline levels of sex hormones after
accounting for sex hormone gene variants on risk of liver disease progression including to
cirrhosis and liver cancer in our baseline HCV+ male cohort from 1-9 years later.
We propose to measure use of commonly prescribed medications that alter levels of androgen
sex hormones like testosterone in the >267,000 males with laboratory confirmed HCV and seen
at the VA between 2000 and 2014. We will extract extensive information about each individual at
baseline to account for their likelihood to ever receive these medications and calculate medication propensity
scores. We will account for these propensity scores in our assessment of the association
between use of these hormone altering medications and risk of HCV-related liver disease
progression from 1-18 years later.
In addition to uncovering new potential therapeutic targets for HCV-related liver disease progression, this
study has rapid and important potential impact on clinical practice in terms of better criteria to risk stratify
veterans and help prioritize them for early access to costly new anti-HCV medications and may alter practice
for prescribing sex hormone altering medications in aging HCV-infected males.

## Key facts

- **NIH application ID:** 9979785
- **Project number:** 5I01CX001430-04
- **Recipient organization:** MICHAEL E DEBAKEY VA MEDICAL CENTER
- **Principal Investigator:** Donna Lorraine White
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-07-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979785

## Citation

> US National Institutes of Health, RePORTER application 9979785, Sex hormones and HCV-related liver disease progression (5I01CX001430-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9979785. Licensed CC0.

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