# Factors Responsible for Liver Recovery After Successful Treatment of Hepatitis C.

> **NIH NIH K23** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2021 · $199,800

## Abstract

Abstract
Advances in the treatment of hepatitis C virus (HCV) have, for the first time, created a situation in which
patients with very advanced disease can readily achieve virological cure. However, preliminary indications
suggest that as many as one third of those patients will continue to progress despite being “cured” of the virus.
The factors that will determine the outcome, and thus the best management, of patients with post-viral,
advanced liver disease are largely unknown. Chronic HCV infection is associated with insulin resistance and
steatosis, which promote fibrosis progression. We postulate that factors associated with fibrosis progression
during the active disease are inversely associated with clinical recovery and fibrosis regression after the
resolution of the active disease. The central hypothesis of this proposal is that the normalization of insulin
resistance and steatosis is central to clinical recovery and fibrosis regression in patients with HCV
cirrhosis, and genetic variability in insulin responsiveness and steatosis accounts for the
heterogeneous responses after treatment of the primary disease. We will prospectively test our
hypothesis by examining the genetic and metabolic characteristics of a large cohort of patients with
decompensated HCV cirrhosis undergoing antiviral treatment. The specific aims are 1) to determine if the
genetic risk factors for steatosis and diabetes influence clinical recovery in patients with decompensated HCV
cirrhosis after successful treatment with a direct-acting antiviral agents based regimen, and 2) to determine if
phenotypic differences in insulin sensitivity influence clinical recovery. An understanding of the genetic factors
that mediate clinical improvement is important for clinical and translational science. Our results will help target
patients for liver transplant evaluation and lead to future therapeutic approaches that improve outcomes for
patients with poor prognostic factors. A second goal of this proposal is to provide a training program that will
allow Dr. Dunn to attain the skills and experiences necessary to become an independent clinical investigator.
The long-term goal is to use patient genomic and phenotypic data for patient-tailored treatment, more accurate
patient-specific prognosis prediction, and optimal targeting of disease-prevention strategies to populations at
highest risk. Dr. Dunn has assembled a multidisciplinary mentoring team that will oversee a program leading to
a Master’s of Science in Clinical Research and further training in statistical genetics. He will also receive
training in scientific communication and the management of a research group. Completion of this 5-year
research and training plan will prepare Dr. Dunn for an independent career as a Physician-Scientist and
Clinical Researcher in the area of personalized medicine for liver disease.

## Key facts

- **NIH application ID:** 10247069
- **Project number:** 5K23DK109294-05
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** Winston Dunn
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $199,800
- **Award type:** 5
- **Project period:** 2017-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247069

## Citation

> US National Institutes of Health, RePORTER application 10247069, Factors Responsible for Liver Recovery After Successful Treatment of Hepatitis C. (5K23DK109294-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10247069. Licensed CC0.

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