# Hepatitis C virus infection and mechanism of liver disease progression

> **NIH NIH R01** · SAINT LOUIS UNIVERSITY · 2020 · $340,875

## Abstract

Abstract
Hepatitis C virus (HCV) often causes persistent infection, and is an increasingly important factor in the
etiology of hepatocellular carcinoma (HCC). There is no preventive or therapeutic hepatitis C vaccine
available. Direct antiviral agents have significantly improved outcome of HCV infection, although it does not
prevent reinfection. Further, the treatment is costly and already faces new issues, such as viral mutation.
Recent studies suggested that some patients still progress to liver failure and/or cancer despite being cured
of infection after therapy. Therefore, studies are extremely urgent to understand the underlying mechanisms
of HCV associated liver pathogenesis. We and others have shown transcriptional regulatory activities of
hepatitis C proteins on a number of cellular genes, which may form the genetic basis for malignant
transformation of infected hepatocytes. Since hepatitis C causes silent disease initially, we do not know when
infected cells transform and who the players are along with viral proteins. Thus, our overall goal in this grant
application is to delineate the mechanisms of hepatitis C mediated HCC. We observed that hepatitis C
modulates microRNAs (miRNA) that can influence hepatocyte growth. We recently observed that hepatitis C
infection of primary human hepatocytes induces phenotypic changes by enhancing epithelial mesenchymal
transition (EMT) related gene expression, and generates tumor initiating stem-like cells (TISCs). Based on
the novel information, we hypothesize that hepatitis C modulates miRNAs and signaling pathways
concurrently to promote hepatocyte growth, leading to HCC progression. We will validate our key
observations using liver biopsy specimens from hepatitis C infected patients to maintain human relevance.
Examining essential steps for inhibition will open up new avenues for developing effective treatment
strategies against this highly prevalent disease.

## Key facts

- **NIH application ID:** 9891052
- **Project number:** 5R01DK113645-04
- **Recipient organization:** SAINT LOUIS UNIVERSITY
- **Principal Investigator:** Ranjit Ray
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $340,875
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9891052

## Citation

> US National Institutes of Health, RePORTER application 9891052, Hepatitis C virus infection and mechanism of liver disease progression (5R01DK113645-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9891052. Licensed CC0.

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