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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA087982-04
Application #
6783348
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Patel, Appasaheb1 R
Project Start
2001-08-01
Project End
2006-07-31
Budget Start
2004-08-01
Budget End
2005-07-31
Support Year
4
Fiscal Year
2004
Total Cost
$593,122
Indirect Cost
Name
Harvard University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02115
Oda, Kohei; Uto, Hirofumi; Kumagai, Kotaro et al. (2014) 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. J Med Virol 86:1877-85
Tsubouchi, Naoko; Uto, Hirofumi; Kumagai, Kotaro et al. (2013) 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. Hepatol Res 43:1130-8
Imakiire, Kazuyuki; Uto, Hirofumi; Sato, Yuko et al. (2012) Difference in serum complement component C4a levels between hepatitis C virus carriers with persistently normal alanine aminotransferase levels or chronic hepatitis C. Mol Med Report 6:259-64
Uto, Hirofumi; Stuver, Sherri O; Hayashi, Katsuhiro et al. (2009) Increased rate of death related to presence of viremia among hepatitis C virus antibody-positive subjects in a community-based cohort study. Hepatology 50:393-9
Takahama, Yuka; Uto, Hirofumi; Kanmura, Shuji et al. (2008) 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. J Gastroenterol 43:942-50
Uto, Hirofumi; Kurogi, Joji; Takahama, Yuka et al. (2007) Alanine aminotransferase flare-up in hepatitis C virus carriers with persistently normal alanine aminotransferase levels in a hyperendemic area of Japan. J Gastroenterol 42:673-80
Kanmura, Shuji; Uto, Hirofumi; Kusumoto, Kazunori et al. (2007) Early diagnostic potential for hepatocellular carcinoma using the SELDI ProteinChip system. Hepatology 45:948-56
Suruki, Robert Y; Mueller, Nancy; Hayashi, Katsuhiro et al. (2006) Host immune status and incidence of hepatocellular carcinoma among subjects infected with hepatitis C virus: a nested case-control study in Japan. Cancer Epidemiol Biomarkers Prev 15:2521-5
Suruki, Robert; Hayashi, Katsuhiro; Kusumoto, Kazunori et al. (2006) Alanine aminotransferase level as a predictor of hepatitis C virus-associated hepatocellular carcinoma incidence in a community-based population in Japan. Int J Cancer 119:192-5
Kusumoto, Kazunori; Uto, Hirofumi; Hayashi, Katsuhiro et al. (2006) Interleukin-10 or tumor necrosis factor-alpha polymorphisms and the natural course of hepatitis C virus infection in a hyperendemic area of Japan. Cytokine 34:24-31

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