We followed 145 men with chronic hepatitis B virus (HBV) hepatitis for 10 years to determine whether exposure to aflatoxin, or concomitant exposure to hepatitis C virus (HCV), or family history of hepatocellular carcinoma (HCC) increased the risk of developing HCC. We collected 8 monthly urine samples before beginning follow-up and pooled them to detect aflatoxin metabolite M1 (AFM1). AFM1 was detected in 78 (54%) of the subjects. The risk of HCC was increased 3.3-fold (with a 95% confidence interval of 1.2-8.7) in those with detectable AFM1 (above 3.6 ng/L). This relative risk was adjusted for age and for HCV status. Hepatocellular carcinoma (HCC) is the second most common cause of death from cancer in China, where the mortality rate was 18 per 100,000 person-years in 1990 through 1992. 1 Infection with hepatitis B virus (HBV) and exposure to aflatoxin are both important risk factors for HCC. Ross et al. 2 studied 18,244 men aged 45 to 64 who lived in Shanghai between 1986 and 1989. In a sample of 140 controls who were age-matched to HCC cases, it was found that 15 (11%) were hepatitis B surface antigen (HBsAg)-positive, and 53 (38%) had detectable urinary aflatoxin metabolites or DNAadducts. A later analysis of 50 HCC cases and 267 agematched controls from this study 3 showed that compared with men without HBsAg or urinary aflatoxin biomarkers, relative risks were 7.3 with 95% a confidence interval (2.2, 24) for those only with HBsAg, 3.4 (1.1, 10) for those only with aflatoxin biomarkers, and 59 (17, 212) for those with both. Based on such data, Ross et al. 2 and Qian et al. 3 suggested that reduction of exposure to aflatoxin might prevent a considerable fraction of the HCC in this population.The previous cohort represented the general male population of Shanghai. We chose instead to follow prospectively a representative group of 145 carriers of HBsAg with a history of chronic hepatitis. These men were being cared for at the Medical Oncology Department of the Qidong Liver Cancer Institute/Hospital, Qidong, Jiangsu Province, China. HCC rates are very high in Qidong. The purpose of the study was to determine whether exposure to aflatoxin increased the risk of HCC or of fatal cirrhosis over a 10-year period in patients with HBV hepatitis. A positive finding would suggest that measures to reduce exposure to aflatoxin might also be beneficial to men with chronic HBV hepatitis and could be evaluated in treatment protocols. Because we collected monthly urine samples for 8 months before beginning follow-up, we were able to pool the samples to obtain estimates of long-term average urinary aflatoxin M1 (AFM1) concentrations, and the assay could detect concentrations of AFM1 as low as 3.6 ng/L. These data also give information on the added risks of HCC in men with chronic HBV hepatitis from exposure to hepatitis C virus (HCV) and from a family history of HCC. PATIENTS AND METHODSPopulation-based sampling was used to obtain a representative study cohort. In an earlier study of the prevalence of HBV infection sponsored by...

No abstract

Qidong City, China, has had high liver cancer incidence from endemic hepatitis B virus (HBV) infection and dietary exposure to aflatoxin. Based on etiologic studies, we began interventions in 1980 to reduce dietary aflatoxin and initiate neonatal HBV vaccination. We studied trends in liver cancer incidence rates in the 1.1 million inhabitants of Qidong and examined trends in aflatoxin exposure, staple food consumption, HBV infection markers and annual income. Aflatoxin exposure declined greatly in association with economic reform, increased earnings and educational programs to shift staple food consumption in the total population from moldy corn to fresh rice. A controlled neonatal HBV vaccination trial began in 1983 and ended in November, 1990, when vaccination was expanded to all newborns. Liver cancer incidence fell dramatically in young adults. Compared with 1980-83, the age-specific liver cancer incidence rates in 2005-08 significantly decreased 14-fold at ages 20-24, 9-fold at ages 25-29, 4-fold at ages 30-34, 1.5-fold at ages 35-39, 1.2-fold at ages 40-44 and 1.4-fold at ages 45-49, but increased at older ages. The 14-fold reduction at ages 20-24 might reflect the combined effects of reduced aflatoxin exposure and partial neonatal HBV vaccination. Decrease incidence in age groups >25 years could mainly be attributable to rapid aflatoxin reduction. Compared with 1980-83, liver cancer incidence in 1990-93 significantly decreased 3.4-fold at ages 20-24, and 1.9-fold at ages 25-29 when the first vaccinees were <11 years old.

The dementia of Alzheimer's type and brain ischemia are known to increase at comparable rates with age. Recent advances suggest that cerebral ischemia may contribute to the pathogenesis of Alzheimer's disease (AD), however, the neuropathological relationship between these two disorders is largely unclear. It has been demonstrated that axonopathy, mainly manifesting as impairment of axonal transport and swelling of the axon and varicosity, is a prominent feature in AD and may play an important role in the neuropathological mechanisms in AD. In this study, we investigated the early and chronic changes of the axons of neurons in the different brain areas (cortex, hippocampus and striatum) using in vivo tracing technique and grading analysis method in a rat model of transient focal cerebral ischemia/reperfusion (middle cerebral artery occlusion, MCAO). In addition, the relationship between the changes of axons and the expression of β-amyloid 42 (Aβ42) and hyperphosphorylated Tau, which have been considered as the key neuropathological processes of AD, was analyzed by combining tracing technique with immunohistochemistry or western blotting. Subsequently, we found that transient cerebral ischemia/reperfusion produced obvious swelling of the axons and varicosities, from 6 hours after transient cerebral ischemia/reperfusion even up to 4 weeks. We could not observe Aβ plaques or overexpression of Aβ42 in the ischemic brain areas, however, the site-specific hyperphosphorylated Tau could be detected in the ischemic cortex. These results suggest that transient cerebral ischemia/reperfusion induce early and chronic axonal changes, which may be an important mechanism affecting the clinical outcome and possibly contributing to the development of AD after stroke.