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Chronic hepatitis B virus (HBV) carriers with high-titer viremia (>10(5) virions/ml) are at increased risk for hepatocellular carcinoma (HCC). The aim of this study was to determine the relationship between clearance of high-titer viremia and subsequent risk of HCC. The study population was a prospective cohort of 114 adults from Haimen City, China, all HBV DNA(+) at study entry and followed for 797.8 person-years in total. During follow-up, 54 (47.4%) subjects spontaneously cleared high-titer viremia at least once. Of these, 27 were considered to have undergone stable seroconversion, 16 were considered unstable (12 reversions to HBV DNA positivity and 4 multiple clearances), and 11 did not have sufficient follow-up to determine stability. Of the 114 persons, 26 (22.8%) died during follow-up, 21 (18.4%) from HCC. Using Cox proportional hazards models, the RR of HCC death associated with seroconversion was 2.8 (95% CI = 1.1-7.4), controlling for age, sex, family HCC history, history of acute hepatitis, alcohol use and cigarette smoking. In conclusion, fluctuations of high-titer viremia may indicate increased hepatocellular damage and at least short-term increases in HCC risk. Long-term longitudinal studies are needed to clarify this relationship and its potential usefulness as a prognostic marker in chronic HBV infection. [ABSTRACT FROM AUTHOR]

Abstract: Fumonisin B1 (FB1), a mycotoxin that contaminates corn in certain climates, has been demonstrated to cause hepatocellular cancer (HCC) in animal models. Whether a relationship between FB1 and HCC exists in humans is not known. To examine the hypothesis, we conducted case-control studies nested within two large cohorts in China; the Haimen City Cohort and the General Population Study of the Nutritional Intervention Trials cohort in Linxian. In the Haimen City Cohort, nail FB1 levels were determined in 271 HCC cases and 280 controls. In the General Population Nutritional Intervention Trial, nail FB1 levels were determined in 72 HCC cases and 147 controls. In each population, odds ratios and 95% confidence intervals (95%CI) from logistic regression models estimated the association between measurable FB1 and HCC, adjusting for hepatitis B virus infection and other factors. A meta-analysis that included both populations was also conducted. The analysis revealed no statistically significant association between FB1 and HCC in either Haimen City (OR=1.10, 95%CI=0.64–1.89) or in Linxian (OR=1.47, 95%CI=0.70–3.07). Similarly, the pooled meta-analysis showed no statistically significant association between FB1 exposure and HCC (OR=1.22, 95%CI=0.79–1.89). These findings, although somewhat preliminary, do not support an associated between FB1 and HCC. [Copyright &y& Elsevier]

Background: Studies in experimental animals suggest that low folate levels may play a role in liver damage and hepatocarcinogenesis. To examine this association in humans, folate levels in blood and risk for subsequent liver damage and hepatocellular carcinoma (HCC) were assessed in a population at high risk of liver cancer in China., Methods: Four hundred fifteen hepatitis B surface antigen-positive participants of the Haimen City Cohort were prospectively followed between 1998 and 2002. Serum and RBC folate levels were determined at baseline. Alanine aminotransferase (ALT) and hepatitis B virus DNA levels were measured semiannually. Logistic regression modeling was used to examine the presence of hepatitis B virus DNA and HCC, whereas linear regression with a log-link function was used to examine ALT levels., Results: There was a statistically significant inverse association between serum folate level and ALT level. ALT levels decreased with each quartile increase in serum folate (adjusted odds ratio, 0.86; 95% confidence interval, 0.76-0.97 for the highest compared with the lowest quartile; Ptrend = 0.002). After exclusion of three persons with prevalent HCC, 20 (4.9%) of the 412 study participants developed HCC during follow-up, with a median time between enrollment and HCC diagnosis of 2.66 years (interquartile range, 1.8-4.1). When comparing persons in the lowest quartile RBC folate to persons in all other quartiles, the analysis found that higher RBC folate levels were associated with reduced risk of hepatocarcinogenesis (odds ratio, 0.33, 95% confidence interval, 0.13-0.86; P(trend) = 0.02)., Conclusions: This study suggests that increased folate levels in humans may be inversely associated with the development of liver damage and HCC.

Background: Studies of chronic hepatitis B virus (HBV) infection in endemic populations have rarely documented causes of mortality other than liver disease and hepatocellular carcinoma (HCC)., Methods: We analysed all-cause mortality related to HBV infection, focusing on the deaths not related to liver disease in a prospective cohort of adults living in Haimen City, China, who were followed from 1992 to 2002. Death certificate data from 4590 deaths among 83 794 individuals were analysed. At cohort entry, 15.0% of the 58 454 male subjects and 10.7% of 25 340 female subjects were hepatitis B surface antigen positive [HbsAg(+)]. HCC and chronic liver disease were the major causes of death in both men and women in this population. The analysis focused on non-liver causes of death., Results: When liver-related causes of death were excluded, there was still a significantly higher age-adjusted death rate among HBsAg(+) individuals. The relative risks (RRs) and 95% confidence intervals (CIs) for all non-liver deaths among HBsAg(+) subjects were 1.2 (1.1-1.3) in men and 1.4 (1.1-1.7) in women. Non-liver causes were further subdivided into cancer and non-cancer groups. For all non-liver cancers, the RR was 1.2 (1.0-1.4) for males and 1.7 (1.2-2.3) for females. Non-liver, non-cancer deaths had RRs of 1.2 (1.1-1.4) and 1.2 (0.9-1.6) in males and females, respectively., Conclusions: HBV-infected individuals may be at increased mortality risk from non-liver causes. Possible reasons include a direct effect of HBV infection, changes in the host immune system as a cause or effect of chronic infection, and behavioural factors associated with HBV infection. Further studies are needed to confirm this finding.

In an 8-year follow-up of a prospective cohort study in Haimen City, China, we sought to identify hepatocellular carcinoma (HCC) risk factors in addition to hepatitis B virus (HBV) infection. Two cohorts of adults between ages 25 and 64 years at study entry were followed from 1992-1993 to 2000. The male cohort included 58,545 men, 15.0% of whom were HBV carriers. The female cohort included 25,340 women, 10.7% of whom were HBV carriers. 434,718 person-years of follow-up were accumulated, and 1092 deaths from HCC occurred. The relationship of potential risk factors measured at study entry to HCC mortality was analyzed using Cox proportional hazards models. For males, HCC mortality was significantly associated with HBV infection [relative risk (RR) 18.8; 95% confidence interval (CI), 15.7-22.5], history of acute hepatitis (RR, 2.3; 95% CI, 2.0-2.7), family history of HCC (RR, 2.3; 95% CI, 1.9-2.7), and occupation as a peasant (RR, 1.5; 95% CI, 1.3-1.8). For females, HCC mortality was significantly associated with HBV infection (RR, 33.5; 95% CI, 17.1-65.5) and acute hepatitis history (RR, 4.7; 95% CI, 3.0-7.5). HCC risk was not significantly associated with alcohol consumption, water source, or staple foods in either sex. There was no association with smoking in males, but there was a positive association for females. Environmental and genetic risk factors besides HBV infection play a significant role in HCC mortality in this extremely high-risk population. Gender differences in HCC mortality and known risk factors are substantial and warrant further study. Identification of risk factors amenable to intervention should be a high priority in the prevention of HCC.