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Grant Details

Grant Number: 5R01CA087982-05 Interpret this number
Primary Investigator: Stuver, Sherri
Organization: Harvard School Of Public Health
Project Title: Hcv Infection-Risk Factors for Progression
Fiscal Year: 2005
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Abstract

DESCRIPTION (provided by applicant): For individuals who are infected with hepatitis C virus (HCV), knowledge of co-factors affecting the occurrence of liver disease is crucial. However, the mechanisms of HCV-associated pathogenesis, particularly with regard to the role of the virus and the host immune response, remain unclear. The primary goal of the proposal is to elucidate the natural history of HCV infection with respect to progression to hepatocellular carcinoma (HCC) and other health outcomes in a Japanese community-based population in which infection with HCV is highly endemic. As part of an annual ultrasonographic tomography screening program in this population, nearly 1,000 adult residents with HCV have been under surveillance for liver cancer since 1994. The proposed study will extend the observation of this cohort, with the additional collection and analysis of virologic, epidemiologic, and clinical data. The specific aims of the research are: to determine the predictive value of markers of HCV infection in the development of liver damage and HCC; to estimate the effect of host-related factors, including heavy alcohol consumption, cigarette smoking, and diet, on HCV-induced liver disease progression and hepatocarcinogenesis; to examine the role of co-infection with hepatitis B virus and human T-lymphotropic virus type I in the natural history of HCV; to characterize the function of host immune status and response in the persistence of HCV infection as well as in the progression of liver disease and HCC among HCV carriers; to evaluate the utility of serologic markers of liver damage in predicting the development of HCC in individuals infected with HCV; to identify predictors of extrahepatic morbidity and mortality among HCV carriers. The uniqueness of the study population and the richness of the data parameters combined with the extensive experience of the assembled multi-disciplinary team provide an important opportunity to increase our understanding of the natural history of HCV and to contribute to our ability to identify and potentially treat those carriers who are at increased risk of an adverse outcome related to their HCV infection.

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Publications

Impact of a single nucleotide polymorphism upstream of the IL28B gene in patients positive for anti-HCV antibody in an HCV hyperendemic area in Japan.
Authors: Oda K. , Uto H. , Kumagai K. , Ido A. , Kusumoto K. , Shimoda K. , Hayashi K. , Stuver S.O. , Tanaka Y. , Nishida N. , et al. .
Source: Journal of medical virology, 2014 Nov; 86(11), p. 1877-85.
EPub date: 2014-08-07.
PMID: 25100136
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Impact of antibody to hepatitis B core antigen on the clinical course of hepatitis C virus carriers in a hyperendemic area in Japan: A community-based cohort study.
Authors: Tsubouchi N. , Uto H. , Kumagai K. , Sasaki F. , Kanmura S. , Numata M. , Moriuchi A. , Oketani M. , Ido A. , Hayashi K. , et al. .
Source: Hepatology research : the official journal of the Japan Society of Hepatology, 2013 Nov; 43(11), p. 1130-8.
EPub date: 2013-02-18.
PMID: 23413835
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Difference in serum complement component C4a levels between hepatitis C virus carriers with persistently normal alanine aminotransferase levels or chronic hepatitis C.
Authors: Imakiire K. , Uto H. , Sato Y. , Sasaki F. , Mawatari S. , Ido A. , Shimoda K. , Hayashi K. , Stuver S.O. , Ito Y. , et al. .
Source: Molecular medicine reports, 2012 Aug; 6(2), p. 259-64.
EPub date: 2012-05-21.
PMID: 22614103
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Increased rate of death related to presence of viremia among hepatitis C virus antibody-positive subjects in a community-based cohort study.
Authors: Uto H. , Stuver S.O. , Hayashi K. , Kumagai K. , Sasaki F. , Kanmura S. , Numata M. , Moriuchi A. , Hasegawa S. , Oketani M. , et al. .
Source: Hepatology (Baltimore, Md.), 2009 Aug; 50(2), p. 393-9.
PMID: 19585614
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Association of a genetic polymorphism in ectonucleotide pyrophosphatase/phosphodiesterase 1 with hepatitis C virus infection and hepatitis C virus core antigen levels in subjects in a hyperendemic area of Japan.
Authors: Takahama Y. , Uto H. , Kanmura S. , Oketani M. , Ido A. , Kusumoto K. , Hasuike S. , Nagata K. , Hayashi K. , Stuver S. , et al. .
Source: Journal of gastroenterology, 2008; 43(12), p. 942-50.
EPub date: 2008-12-24.
PMID: 19107338
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Alanine aminotransferase flare-up in hepatitis C virus carriers with persistently normal alanine aminotransferase levels in a hyperendemic area of Japan.
Authors: Uto H. , Kurogi J. , Takahama Y. , Kusumoto K. , Hayashi K. , Ido A. , Kohara M. , Stuver S.O. , Moriuchi A. , Hasegawa S. , et al. .
Source: Journal of gastroenterology, 2007 Aug; 42(8), p. 673-80.
EPub date: 2007-08-24.
PMID: 17701131
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Early diagnostic potential for hepatocellular carcinoma using the SELDI ProteinChip system.
Authors: Kanmura S. , Uto H. , Kusumoto K. , Ishida Y. , Hasuike S. , Nagata K. , Hayashi K. , Ido A. , Stuver S.O. , Tsubouchi H. .
Source: Hepatology (Baltimore, Md.), 2007 Apr; 45(4), p. 948-56.
PMID: 17393466
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Host immune status and incidence of hepatocellular carcinoma among subjects infected with hepatitis C virus: a nested case-control study in Japan.
Authors: Suruki R.Y. , Mueller N. , Hayashi K. , Harn D. , DeGruttola V. , Raker C.A. , Tsubouchi H. , Stuver S.O. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2006 Dec; 15(12), p. 2521-5.
PMID: 17164379
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Alanine aminotransferase level as a predictor of hepatitis C virus-associated hepatocellular carcinoma incidence in a community-based population in Japan.
Authors: Suruki R. , Hayashi K. , Kusumoto K. , Uto H. , Ido A. , Tsubouchi H. , Stuver S.O. .
Source: International journal of cancer, 2006-07-01; 119(1), p. 192-5.
PMID: 16432841
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Interleukin-10 or tumor necrosis factor-alpha polymorphisms and the natural course of hepatitis C virus infection in a hyperendemic area of Japan.
Authors: Kusumoto K. , Uto H. , Hayashi K. , Takahama Y. , Nakao H. , Suruki R. , Stuver S.O. , Ido A. , Tsubouchi H. .
Source: Cytokine, 2006 Apr; 34(1-2), p. 24-31.
EPub date: 2006-05-15.
PMID: 16698276
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Usefulness of a new immuno-radiometric assay to detect hepatitis C core antigen in a community-based population.
Authors: Hayashi K. , Hasuike S. , Kusumoto K. , Ido A. , Uto H. , Kenji N. , Kohara M. , Stuver S.O. , Tsubouchi H. .
Source: Journal of viral hepatitis, 2005 Jan; 12(1), p. 106-10.
PMID: 15655057
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