Chronic carriers of hepatitis B virus (HBV) are at increased risk for hepatocellular carcinoma (HCC). Worldwide, however, the risk of HCC and other adverse outcomes varies substantially both between and within populations of HBV carriers. The reasons for these differences in the natural history of infection are not known. Our analysis of cohort studies in three endemic populations have suggested that the long term maintenance of high-titer viremia (i.e., equal to or > 1 pg/ml) is an important predictor of HCC. The mechanism behind the maintenance of viremia is, however, not well understood although it is clear that the host immune response plays a key role. In this application, we focus on molecular variants of the virus itself and polymorphisms of human immunoregulatory genes as potential predictive or explanatory factors in maintenance of viremia. We will draw upon established prospective cohorts of chronic HBV carriers in China, West Africa, and Asian- Americans. Our preliminary data support a relationship between deletions in the C ORF of HBV and clearance of active viral replication. In the proposed project we will test this hypothesis and extend our studies of molecular variation of HBV by application of novel statistical methods to sequence data. We will also test the hypothesis that maintenance of HBV viremia is associated with polymorphisms of the vitamin D receptor (VDR) and tumor necrosis factor alpha (TNFalpha) promoter. Allele frequencies for polymorphisms of lesser-studied immunomodulatory genes in our cohorts will be estimated in order to develop hypotheses about their relationship to maintenance of viremia in HBV carriers.
| Chen, Gang; Lin, Wenyao; Shen, Fumin et al. (2006) Past HBV viral load as predictor of mortality and morbidity from HCC and chronic liver disease in a prospective study. Am J Gastroenterol 101:1797-803 |
| Chen, Gang; Lin, Wenyao; Shen, Fumin et al. (2005) Chronic hepatitis B virus infection and mortality from non-liver causes: results from the Haimen City cohort study. Int J Epidemiol 34:132-7 |
| Tang, Baiqing; Kruger, Warren D; Chen, Gang et al. (2004) Hepatitis B viremia is associated with increased risk of hepatocellular carcinoma in chronic carriers. J Med Virol 72:35-40 |
| Harris, Rebecca A; Chen, Gang; Lin, Wen Yao et al. (2003) Spontaneous clearance of high-titer serum HBV DNA and risk of hepatocellular carcinoma in a Chinese population. Cancer Causes Control 14:995-1000 |
