Estimation on disease burden related to hepatitis B virus infection in Shandong province of China [山东省乙型肝炎病毒感染所致相关疾病的疾病负担研究]

Objective: To comprehensively measure the burden of hepatitis B, liver cirrhosis and liver cancer in Shandong province, using disability-adjusted life years (DALYs) to estimate the disease burden attribute to hepatitis B virus (HBV)infection. Methods: Based on the mortality data of hepatitis B, liver cirrhosis and liver cancer derived from the third National Sampling Retrospective Survey for Causes of Death during 2004 and 2005, the incidence data of hepatitis B and the prevalence and the disability weights of liver cancer gained from the Shandong Cancer Prevalence Sampling Survey in 2007, we calculated the years of life lost (YLLs), years lived with disability (YLDs) and DALYs of three diseases following the procedures developed for the global burden of disease (GBD) study to ensure the comparability. Results: The total burden for hepatitis B, liver cirrhosis and liver cancer were 211 616 (39 377 YLLs and 172 239 YLDs), 16 783 (13 497 YLLs and 3286 YLDs) and 247 795 (240 236 YLLs and 7559 YLDs) DALYs in 2005 respectively, and men were 2.19, 2.36 and 3.16 times as that for women, respectively in Shandong province. The burden for hepatitis B was mainly because of disability (81.39%). However, most burden on liver cirrhosis and liver cancer were due to premature death (80.42% and 96.95%). The burden of each patient related to hepatitis B, liver cirrhosis and liver cancer were 4.8, 13.73 and 11.11 respectively. Conclusion: Hepatitis B, liver cirrhosis and liver cancer caused considerable burden to the people living in Shandong province, indicating that the control of hepatitis B virus infection would bring huge potential benefits.

Detection of hepatitis B virus markers using a biosensor based on imaging ellipsometry

A biosensor based on imaging ellipsometry (BIE) has been developed and validated in 169 patients for detecting five markers of hepatitis B virus (HBV) infection. The methodology has been established to pave the way for clinical diagnosis, including ligand screening, determination of the sensitivity, set-up of cut-off values (CoVs) and comparison with other clinical methods. A matrix assay method was established for ligand screening. The CoVs of HBV markers were derived with the help of receiver operating characteristic curves. Enzyme-linked immunosorbent assay (ELISA) was the reference method. Ligands with high bioactivity were selected and sensitivities of 1 ng/mL and 1 IU/mL for hepatitis B surface antigen (HBsAg) and surface antibody (anti-HBs) were obtained respectively. The CoVs of HBsAg, anti-HBs, hepatitis B e antigen, hepatitis B e antibody and core antibody were as follows: 15%, 18%, 15%, 20% and 15%, respectively, which were the percentages over the values of corresponding ligand controls. BIE can simultaneously detect up to five markers within 1 h with results in acceptable agreement with ELISA, and thus shows a potential for diagnosing hepatitis B with high throughput.

Stability and molecular modeling of triplex DNA inhibiting DNA binding protein binding to the core promoter of hepatitis B virus.

Two three-dimensional structure models of the 21nt oligodeoxyribonucleotides, CPI (G3TG-2TGT2G5TG2TGT) and CP3 (TGTG2TGST2GTG2TG3), were constructed by InsightII (MSI) software in IRIS Indigo2 (SGI) workstation using the crystal structure of TAT tripler formation as the template. The initial structures subsequently were minimized by molecular mechanics. The final structures were believed as the dominant conformation. The results showed that the energy of CP1 is lower than that of CP3, and the former is more stable than the latter. Moreover, the results further proved that the 21nt oligodeoxyribo-nucleotide CP1 stably combines with the core promoter (Cp) fragment of hepatitis B virus (HBV) to form a tripler DNA, and CP1 specifically inhibits a specific cellular factor (DNA binding protein) binding to Cp fragment. These results indicated that specific repression of gene transcription of HBV DNA might be possible by tripler-formation DNA.

TP53 R249S Mutations, Exposure to Aflatoxin, and Occurrence of Hepatocellular Carcinoma in a Cohort of Chronic Hepatitis B Virus Carriers from Qidong, China

Hepatocellular carcinoma (HCC) has a high mortality in East Asia and Sub-Saharan Africa, two regions where the main etiologic factors are chronic infections with hepatitis B vir-us and dietary exposure to aflatoxin. A single base substitution at the third nucleotide of codon 249 of TP53 (R249S) is common in HCC in these regions and has been associated with aflatoxin-DNA adducts. To determine whether R249S may be detected in plasma DNA before HCC diagnosis, we conducted a case-control study nested in a cohort of adult chronic hepatitis B virus carriers from Qidong County, People's Republic of China. Of the 234 plasma specimens that yielded adequate DNA, only 2 (0.9%) were positive for R249S by restriction fragment length polymorphisms, and both of them were controls. Of the 249 subjects tested for aflatoxin-albumin adducts, 168 (67%) were positive, with equal distribution between cases and controls. Aflatoxin-albumin adduct levels were low in the study, suggesting an overall low ongoing exposure to aflatoxin in this cohort. The R249S mutation was detected in 11 of 18 (61%) available tumor tissues. To assess whether low levels of mutant DNA were detectable in pre-diagnosis plasma, 14 plasma specimens from these patients were analyzed by short oligonucleotide mass analysis. Nine of them (64%) were found to be positive. Overall, these results suggest that HCC containing R249S can occur in the absence of significant recent exposure to aflatoxins. The use of short oligonucleotide mass analysis in the context of low ongoing aflatoxin exposure may allow the detection of R249S in plasma several months ahead of clinical diagnosis. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1638-43)

Hepatocellular carcinoma and polymorphisms in carcinogen-metabolizing and DNA repair enzymes in a population with aflatoxin exposure and hepatitis B virus endemicity

High rates of hepatocellular carcinoma (HCC) in The Gambia, West Africa, are primarily due to a high prevalence of chronic hepatitis B virus infection and heavy aflatoxin exposure via groundnut consumption. We investigated genetic polymorphisms in carcinogen-metabolizing (GSTM1, GSTT1, HYL1*2) and DNA repair (XRCC1) enzymes in a hospital-based case-control study. Incident HCC cases (n = 216) were compared with frequency-matched controls (n = 408) with no clinically apparent liver disease. Although the prevalence of variant genotypes was generally low, in multivariable analysis (adjusting for demographic factors, hepatitis B virus, hepatitis C virus, and TP53 status), the GSTM1-null genotype [odds ratio (OR), 2.45; 95% confidence interval (95% CI), 1.21-4.95] and the heterozygote XRCC1-399 AG genotype (OR, 3.18; 95% CI, 1.35-7.51) were significantly associated with HCC. A weak association of the HYL1*2 polymorphism with HCC was observed but did not reach statistical significance. GSTT1 was not associated with HCC. The risk for HCC with null GSTM1 was most prominent among those with the highest groundnut consumption (OR, 4.67; 95% CI, 1.45-15.1) and was not evident among those with less than the mean groundnut intake (OR, 0.64; 95% Cl, 0.20-2.02). Among participants who had all three suspected aflatoxin-related high-risk genotypes [GSTM1 null, HLY1*2 (HY/HH), and XRCC1 (AG/GG)], a significant 15-fold increased risk of HCC was observed albeit with imprecise estimates (OR, 14.7; 95% CI, 1.27-169). Our findings suggest that genetic modulation of carcinogen metabolism and DNA repair can alter susceptibility to HCC and that these effects may be modified by environmental factors.

Hepatitis B Virus transmission and hepatocarcinogenesis: a 9 year retropective cohort of 13676 relatives with hepatocellular carcinoma

<b>Background/Aims b><br />Familial clustering of hepatitis B virus (HBV) infection is related to perinatal transmission, and is the main cause of familial-type hepatocellular carcinoma (HCC). The route of HBV transmission differs between the children and siblings of patients with HCC. This study examined the differences in HBV carrier rates and HCC-related mortality between two generations in HCC families.<br /><b>Methods b><br />From 1992 to 1997, relatives of individuals with HCC were screened prospectively with ultrasonography, alpha-fetoprotein, liver biochemistry tests and viral markers. Total HCC-related deaths during a 9-year period were compared between the generations of index patients and their children.<br /><b>Results b><br />The study included a total of 13 676 relatives in two generations. More HCC-related deaths occurred in the index patient generation than in the child generation. Furthermore, children of female index patients had higher rates of liver cancer related mortality than children of male index patients. The same was true when the analysis was limited to male HBV carriers. The prevalence of HBsAg in the offspring of HBsAg positive mothers was 66% in the child generation and 72% in the index patient generation. These high prevalences indicated high maternal HBV replication status.<br /><b>Conclusions b><br />Perinatal transmission and maternal viral load are important risk factors in hepatocarcinogenesis.<br />

The current pattern of hepatitis B virus infectiion in Australia

Summary. There is little recent data of the seroprevalence of hepatitis B in Australia. We have surveyed a large cohort of endoscopy patients attending a teaching hospital in central Sydney, and related the presence of hepatitis B virus (HBV) markers with putative risk factors for exposure using the SAS statistical package. Of the 2115 patients tested: 2.1% (45/2115) were HBV surface antigen positive, 0.75% (14/2115) viraemic, 9.5% (200/2115) anti-HBs and anti-HBc positive, 20.1% (430/2115) vaccinated (anti-HBs only) and the remaining 70% were susceptible. The adjusted OR of HBV infection was significantly increased in patients who had been diagnosed with human immunodeficiency virus (36.3-fold), born in Asia or Pacific islands (12.4-fold), born in North Africa, Middle East & Mediterranean countries (6-fold) or born abroad elsewhere in the world (2.7-fold), had household contact with someone diagnosed with hepatitis between 1980 and 1990 (3.9-fold), injected drugs between 1980 and 1990 (4.4-fold), resided in a military establishment for 3 months (2.3-fold) or in a hospital for 3 months (2.2-fold), never been vaccinated for hepatitis B (2.8-fold), received blood transfusion due to an accident and/or a haemorrhage (1.92-fold) and finally been a male gender (1.59-fold). The prevalence of HBV in this hospital population was higher than predicted on the basis of notifications to the passive surveillance scheme. Most HBV patients had multiple risk factors for infection, but the hierarchy of odds ratios provides a rational basis for targeted programmes to identify asymptomatic HBV carriers who might benefit from treatment.

Targeting hepatitis B virus and human papillomavirus induced carcinogenesis : novel patented therapeutics

Viral infections leading to carcinogenesis tops the risk factors list for the development of human cancer. The decades of research has provided ample scientific evidence that directly links 10-15% of the worldwide incidence of human cancers to the infections with seven human viruses. Moreover, the insights gained into the molecular pathogenetic and immune mechanisms of hepatitis B virus (HBV) and human papillomavirus (HPV) viral transmission to tumour progression, and the identification of their viral surface antigens as well as oncoproteins have provided the scientific community with opportunities to target these virus infections through the development of prophylactic vaccines and antiviral therapeutics. The preventive vaccination programmes targeting HBV and high risk HPV infections, linked to hepatocellular carcinoma (HCC) and cervical cancer respectively have been recently reported to alter age-old cancer patterns on an international scale. In this review, with an emphasis on HBV and HPV mediated carcinogenesis because of the similarities and differences in their global incidence patterns, viral transmission, mortality, molecular pathogenesis and prevention, we focus on the development of recently identified HBV and HPV targeting innovative strategies resulting in several patents and patent applications.<br />

Transgenic lettuce seedlings carrying hepatitis B virus antigen HBsAg

The obtainment of transgenic edible plants carrying recombinant antigens is a desired issue in search for economic alternatives viewing vaccine production. Here we report a strategy for genetic transformation of lettuce plants (Lactuca sativa L.) using the surface antigen HBsAg of hepatitis B virus. Transgenic lettuce seedlings were obtained through the application of a regulated balance of plant growth regulators. Genetic transformation process was acquired by cocultivation of cotyledons with Agrobacterium tumefaciens harboring the recombinant plasmid. It is the first description of a lettuce Brazilian variety Vitória de Verão genetically modified.

Serologic profile in hepatitis B virus and hepatitis C virus in a Brazilian liver transplant waiting list

Chronic viral hepatitis is currently the most common indication for liver transplantation (OLT). Knowing the serological profile of patients on the liver transplant waiting list (LTWL) is essential to manage prophylactic and therapeutic strategies pre- and post-OLT. The aim of this study was to determine the hepatitis B virus (HBV) and hepatitis C virus (HCV) serological profile on the LTWL.Methods. Serological data were collected from 44 candidates included on, the LTWL from May 2003 to November 2004. HBV and HCV serological profiles were performed by microenzyme immunoassay.Results. Twenty-eight patients (66.7%) lacked H13V serological markers. Anti-HBs was detected in 9.5% and was positive for HBsAg, anti-HBc, IgM anti-HBc, or HbeAg in 4.8% of patients, probably related to reactivation of chronic infection. In 7.1% of patients, the markers demonstrated serological cure of infection. In HCV patients, 41.5% were positive. There was H13V and HCV co-infection in 12.2% of patients.Conclusion. HBV infection in 21.4% of the patients corroborates the need to use more efficient protocols for prophylactic and therapeutic management pre- and post-OLT. The high prevalence of HCV infection reinforces the need to follow adequate protocols to avoid related complications and guarantee rational and universal use of more efficient drugs.

Liver HLA-G expression is associated with multiple clinical and histopathological forms of chronic hepatitis B virus infection

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

A possible correlation between the host genetic background in the epidemiology of Hepatitis B virus in the Amazon region of Brazil

ABSTRACT: The Amazon region of Brazil is an area of great interest because of the large distribution of hepatitis B virus in specific Western areas. Seven urban communities and 24 Indian groups were visited in a total of 4,244 persons. Each individual was interviewed in order to obtain demographic and familial information. Whole blood was collected for serology and genetic determinations. Eleven genetic markers and three HBV markers were tested. Among the most relevant results it was possible to show that (i) there was a large variation of previous exposure to HBV in both urban and non-urban groups ranging from 0 to 59.2%; (ii) there was a different pattern of epidemiological distribution of HBV that was present even among a same linguistic Indian group, with mixed patterns of correlation between HBsAg and anti-HBs and (iii) the prevalence of HBV markers (HBsAg and anti-HBs) were significantly higher (P=0.0001) among the Indian population (18.8%) than the urban groups (12.5%). Its possible that the host genetic background could influence and modulate the replication of the virus in order to generate HB carrier state.

Prevalence of hepatitis B virus infection and carriage after nineteen years of vaccination program in the Western Brazilian Amazon

Introduction: Reductions in the prevalence of hepatitis B virus (HBV) infection and carriage, decreases in liver cancer incidence, and changes in patterns of liver dysfunctions are described after hepatitis B vaccination. Methods: We conducted a population-based seroprevalence study aimed at estimating the HBV prevalence and risk of infection in the rural area of Labrea following nineteen years of HBV vaccination. Results: Half of the subjects showed total anti-HBc of 52.1% (95% CI 49.6-54.7). The HBsAg prevalence was 6.2% (95% CI 5.1-7.6). Multivariate analysis showed an inverse association between HBV infection and vaccination (OR 0.62; 95% CI 0.44-0.87). HBsAg remained independently associated with past hepatitis (OR 2.44; 95% CI 1.52-3.89) and inversely to vaccination (OR 0.43; 95% CI 0.27-0.69). The prevalence of HBeAg among HBsAg-positive individuals was 20.4% (95% CI 12.8-30.1), with the positive subjects having a median age of 11 years (1-46) p=0.0003. Conclusions: We demonstrate that HBV infection is still an important public health issue and that HBV vaccination could have had better impact on HBV epidemiology. If we extrapolate these findings to other rural areas in the Brazilian Amazon, we can predict that the sources of chronic infected patients remain a challenge. Future studies are needed regarding clinical aspects, molecular epidemiology, surveillance of acute cases, and risk groups.

Hepatitis B virus genotypes from European origin explains the high endemicity found in some areas from southern Brazil

Southern Brazil is considered an area of low Hepatitis B endemicity, but some areas of higher endemicity have been described in the Southwest of Parana and Santa Catarina states. The aim of this study was to evaluate viral genotypes circulating throughout Parana state. PCR amplification and partial sequencing of the S gene was carried out in 228 samples from HBsAg positive candidate blood donors. Samples have been collected in seven different counties (Cascavel, Curitiba, Foz do Iguacu, Francisco Beltrao, Matinga Londrina and Paranagua). The most common HBV genotype in Parana state was D (82.9%; 189/228), followed by A (14.1%; 32/228). Genotypes F (1.3%; 3/228), C (1.3%; 3/228) and H (0.4%; 1/228) were also found. Distribution of genotypes was different in the studied counties, but genotype D was the most frequent in all of them. In Francisco Beltrao, all studied samples belonged to genotype D. The high prevalence of HBV genotype Din South of Brazil is explained by the intense migration of settlers from Europeans countries. Subgenotypes A1 and A2 were identified circulating in all cities where HBV/A was found. As observed in other areas of Brazil, HBV/A1 is more frequent than the HBV/A2 in Parana state and its presence was significantly larger in black and mulatto individuals. Genotype C was found only in individuals with Asian ancestry from Londrina and Maringa. Most HBV/F sequences identified in this study were classified as subgenotype F2a that was previously described in Brazil. The sole case of subgenotype F4 was from Foz do Iguacu city, near to Northern Argentina, where F4 is highly prevalent. The single genotype H sample was from Curitiba. This is the first case of this genotype described in Brazil. Further studies should be carried out to determine if more genotype H samples can be found in other populations from Brazil. (C) 2012 Elsevier B.V. All rights reserved.