Abstract

Up to 3% of the world population is infected with hepatitis C virus (HCV), a hepatotropic RNA virus that causes acute and chronic hepatitis as well as cirrhosis and hepatocellular carcinoma. HCV infection results in chronicity in most cases (85%) despite detectable antiviral immune response, and recent studies suggest that virus-specific T cells play an important role in the outcome of HCV infection. Interestingly, HCV infection is up to 7 fold more prevalent in alcoholic individuals than in the general population, and chronic alcohol use in HCV-infected patients is associated with accelerated liver disease progression and development of liver cancer. While alcohol is known to suppress cellular immune response, little is known about the effect of alcohol on HCV-specific T cell response in HCV-infected patients. Therefore, the primary aim of this application is to determine if chronic alcohol use results in a pathogenetic HCV-specific T cell response that promotes further liver damage than virus control. In addition, we will determine the extent to which this may be reversed upon alcohol cessation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA012849-02
Application #
6371838
Study Section
Special Emphasis Panel (ZAA1-DD (01))
Program Officer
Lucas, Diane
Project Start
2000-09-28
Project End
2005-07-31
Budget Start
2001-08-01
Budget End
2002-07-31
Support Year
2
Fiscal Year
2001
Total Cost
$370,433
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Ojiro, Keisuke; Qu, Xiaowang; Cho, Hyosun et al. (2017) Modulation of Hepatitis C Virus-Specific CD8 Effector T-Cell Function with Antiviral Effect in Infectious Hepatitis C Virus Coculture Model. J Virol 91:
Bunchorntavakul, Chalermrat; Jones, Lisa M; Kikuchi, Masahiro et al. (2015) Distinct features in natural history and outcomes of acute hepatitis C. J Clin Gastroenterol 49:e31-40
Cho, Hyosun; Kikuchi, Masahiro; Li, Yun et al. (2014) Induction of Multiple Immune Regulatory Pathways with Differential Impact in HCV/HIV Coinfection. Front Immunol 5:265
Doi, Hiroyoshi; Iyer, Tara K; Carpenter, Erica et al. (2012) Dysfunctional B-cell activation in cirrhosis resulting from hepatitis C infection associated with disappearance of CD27-positive B-cell population. Hepatology 55:709-19
Kaplan, David E; Ikeda, Fusao; Li, Yun et al. (2008) Peripheral virus-specific T-cell interleukin-10 responses develop early in acute hepatitis C infection and become dominant in chronic hepatitis. J Hepatol 48:903-13
Harris, Rebecca A; Sugimoto, Kazushi; Kaplan, David E et al. (2008) Human leukocyte antigen class II associations with hepatitis C virus clearance and virus-specific CD4 T cell response among Caucasians and African Americans. Hepatology 48:70-9
Ebinuma, Hirotoshi; Nakamoto, Nobuhiro; Li, Yun et al. (2008) Identification and in vitro expansion of functional antigen-specific CD25+ FoxP3+ regulatory T cells in hepatitis C virus infection. J Virol 82:5043-53
Nakamoto, Nobuhiro; Kaplan, David E; Coleclough, Jennifer et al. (2008) Functional restoration of HCV-specific CD8 T cells by PD-1 blockade is defined by PD-1 expression and compartmentalization. Gastroenterology 134:1927-37, 1937.e1-2
Kaplan, David E; Sugimoto, Kazushi; Newton, Kimberly et al. (2007) Discordant role of CD4 T-cell response relative to neutralizing antibody and CD8 T-cell responses in acute hepatitis C. Gastroenterology 132:654-66
Merriman, Nathan A; Porter, Steven B; Brensinger, Colleen M et al. (2006) Racial difference in mortality among U.S. veterans with HCV/HIV coinfection. Am J Gastroenterol 101:760-7

Showing the most recent 10 out of 18 publications