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ARRA Investments in Hepatitis


Public Health Burden
Hepatitis, or inflammation of the liver, is most often caused by infection of a diverse group of viruses that include hepatitis A, B, C, D, E, G and GB viruses. Some of these viruses, like hepatitis A and E, are transmitted through contaminated food and water. Others, such as hepatitis B and C, are blood-borne and can cause chronic inflammation that may progress to cirrhosis and hepatic cancers. These three viruses continue to afflict more than half a billion people worldwide and result in more than a million deaths each year.

Basic Research
With the development of animal models, cell culture systems, and new reagents, scientists have valuable tools that can be used to advance our basic understanding of hepatitis viruses and the human response to hepatitis infections. ARRA-funded grants contributing to progress in this area include projects aimed at:
  • Developing a system in mice to explore how hepatitis C virus (HCV) replicates in the cells of the liver and how it interacts with the host’s immune system. This research will help to evaluate the efficacy of HCV therapeutics.1
  • Testing how the activity of specific cell-types in the immune system contributes to the development of autoimmune hepatitis. 2
  • Introducing a novel cell culture system to study the replication of HCV; this system can be used to develop more effective interventions. 3
  • Improving the growth of HCV in cell culture and developing a convenient method for measuring infectious HCV particles. 4
  • Designing novel proteins that help the immune system eliminate HCV and other viral infections like HIV. 5
Treatment
ARRA-supported projects are focusing on developing new vaccines and therapies to prevent and combat acute and chronic hepatitis infections, including research projects that aim to:
  • Provide insights into the mechanism of immune-cell dysfunction in chronic hepatitis and the underlying causes of persistence of HCV infection. Findings from this research may advance efforts to develop treatments for HCV infection. 6
  • Improve our understanding of how HCV interferes with the normal regulation of immune cells, potentially leading to virus-induced autoimmunity and malignancy. 7
  • Explore a novel approach to develop a therapeutic vaccine for HCV. 8
  • Develop a novel drug discovery system that identifies compounds that inhibit the formation of a specific DNA structure that is essential for the life cycle of hepatitis B virus (HBV). 9
  • Investigate how two key enzymes—hepatic lipase and lipoprotein lipase – affect HCV infection and contribute to fat accumulation in the liver (an effect associated with chronic HCV infection). 10
  • Determine if the heightened oxidative stress associated with HCV infection contributes to liver fibrosis, cirrhosis, and ultimately liver cancer. 11
Co-infection with HIV
Nearly one third of individuals infected with HIV are co-infected with HCV, and hepatitis-related liver disease is one of the leading causes of death in co-infected individuals. ARRA-funded projects support research exploring hepatitis virus/ HIV co-infections. Some examples include studies that:
  • Examine the effectiveness of combination therapies used to treat patients co-infected with HIV and HBV by measuring HBV levels in blood samples from co-infected patients who participated in longitudinal HIV clinical trials. 12
  • Determine the role of HBV genotype in HIV/HBV treatment outcomes in a resource-limited setting with the hope of improving future diagnostic and therapeutic strategies in HIV/HBV co-infection. 13
  • Seek to improve the understanding of how co-infection with the hepatitis GB virus prolongs the lives of individuals infected with HIV. 14
  • Investigate how co-infection with HIV affects the replication and pathogenesis of the HCV in a mouse model which will assist in identifying novel treatment strategies in controlling HCV diseases. 15



  1. 1R21AI068999-01A2 -- Directed Evolution of a Murine Model of Hepatitis C Virus Replication -- Yang, Priscilla Li-Ning (MA)
  2. 1R21AI078195-01A1S1 -- Chemokines in Autoimmune Hepatitis -- Gorham, James D (NH)
  3. 1F31AI081530-01A -- Novel Culture System for Hepatitis C Virus -- Klepper, Arielle (NY)
  4. 3R21AI065535-02S1 -- Developing an In Vitro System for HCV propagation -- Ray, Ratna B (MO)
  5. 1R21AI081065-01A1 -- Structure and Design of Cytokine and Chemokine Binding Proteins -- Walter, Mark R (AL)
  6. 2R01AI047519-11 -- Cellular Immunity and the Outcome of Hepatitis C Virus Infection -- Chang, Kyong-Mi (PA)
  7. 3K08AI075031-02S1 -- The Pathogenesis of Autoimmunity in Hepatitis C Virus Infection -- Charles, Edgar D (NY)
  8. 1R21AI082349-01 -- Targeting pDCs for the Generation of Effective Anti-HCV CD8+ T-Cell Immunity -- Connolly, John E (TX)
  9. 3R56AI066024-01A2S1 -- Screen for an Unexploited Step in the HBV Life Cycle -- Cuconati, Andrea (PA)
  10. 1R21AI083389-01 -- Hepatic Lipase and HCV Infection -- Wang, Tianyi (PA)
  11. 1R21AI078532-01A2 -- Hepatitis C Virus and Liver Fibrogenesis -- Waris, Gulam (IL)
  12. 1R21AI083106-01 -- Virologic and Serologic Outcomes of Persons with HIV and HBV co-infection on Mono -- Aberg, Judith Ann (NY)
  13. 3K23AI066983-02S1 -- HIV and Hepatitis B Coinfection: Hepatitis B Genotype, Resistance and Outcomes -- Bhattacharya, Debika (CA)
  14. 2R01AI058740-06A1 -- GBV-C Effects on CD4 Activation and Expansion -- Stapleton, Jack T (IA)
  15. 1R21AI076142-01A1 -- Pathogenesis of HCV in a Novel Mouse Model -- Su, Lishan (NC)


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Page Last Updated on June 30, 2018 NIH...Turning Discovery Into Health®