Yongping Yan

Mother-to-infant transmission of hepatitis B virus: a Chinese experience.

Over 90% of infants infected with hepatitis B virus (HBV) caused by mother‐to‐infant transmission will evolve to carrier status, and this cannot be prevented until widespread administration of the HB vaccine and hepatitis B immune globulin (HBIG) is implemented. This prospective study of 214 infants born to HBsAg‐positive mothers was carried out to determine if either perinatal or intrauterine HBV transmission could be effectively prevented with HBIG and the HB vaccine. Peripheral blood was collected from mothers and from newborns before they received HBIG and the HB vaccine, as well as at 0, 1, 7, 24, and 36 months after birth. Infants born with an ratio of signal to noise(S/N) value of >5 for HBsAg (ABBOTT Diagnostic Kit) were defined as mother‐to‐infant transmission cases, those with an S/N between 5 and 50 were classified as perinatal transmission cases, and those with an S/N >50 were considered intrauterine transmission cases. Mother‐to‐infant transmission occurred in approximately 4.7% (10/214) of the infants; the perinatal transmission and intrauterine transmission rates were 3.7% (8/214) and 0.9% (2/214), respectively. The risk of mother‐to‐infant transmission increased along with maternal HBeAg or HBVDNA levels. After 36 months of follow‐up, all perinatal cases became HBsAg‐negative, whereas all intrauterine transmission cases evolved into carrier status. These results indicate that infants infected via intrauterine transmission cannot be effectively protected by HBIG and HB vaccine. J. Med. Virol. 83:791–795, 2011.

Analysis of recombination and natural selection in human enterovirus 71

The development of effective vaccines and antiviral prophylaxis against human enterovirus 71 (EV71) has been hampered by the extensive antigenic diversity of the virus. To gain new insights into the evolutionary processes that create this genetic diversity, the TreeOrder Scan Method and RDP program were employed to detect recombination events in the genome, and then parsimony-based and maximum-likelihood-based methods were used to detect natural selection effects on viral proteins. Recombination analysis provided strong evidence for recombination events in the majority of the sequences analyzed. Recombination events were found to be distributed nonrandomly with the highest frequency at the 3D region. Furthermore, positive selection was only detected at site 145 of VP1 by the maximum likelihood-based method. These results reveal that EV71 proteins are extensively influenced by stabilizing selection. We conclude that recombination may play a more important role than positive selection in the formation of genetic diversity.

Occult Hepatitis B Virus Infection in Anti-HBs-Positive Infants Born to HBsAg-Positive Mothers in China

Objective To investigate the prevalence of occult HBV infection (OBI) among children and to characterize virology of occult HBV, we conducted an epidemiological survey. Methods 186 HB-vaccinated infants born to HBsAg-positive mothers were included in the study. Serological tests for HBV markers were performed using commercial ELISA kits. Real-time quantitative PCR and nested PCR were used to detect HBV DNA. PCR products of the C and pre-S/S regions were sequenced and analyzed. Results 1.61% (3/186) infants were HBsAg positive, and 4.92% (9/183) infants were considered as occult infection. The viral load of mothers was associated with occult infection (P = 0.020). Incomplete three-dose injections of HB vaccine was associated with HBV infection (P = 0.022). Six OBI infants were positive for anti-HBs, but their titers were not greater than 100 mIU/mL. Seven isolated HBV pre-S/S sequences were obtained from nine OBI infants. Three of the sequences were genotype C, and four of the sequences were genotype C/D. Escape mutation S143L was found in the four sequences of genotype C/D. All seven sequences lacked G145R and other escape mutation in S region. Conclusions Occult HBV infection was detected in anti-HBs positive infants born to HBsAg-positive mothers in China. Occult infection was associated with absent anti-HBs or with low anti-HBs level, high maternal viral loads and escape mutations in the S gene.

Association between genomic heterogeneity of hepatitis B virus and intrauterine infection.

Hepatitis B virus (HBV) intrauterine infection remains to be an important cause for a large number of persistent hepatitis B surface antigen (HBsAg) positive carriers in areas with a high HBV prevalence, particularly in China and Southeast Asia. In this study, the possible association between the HBV genomic heterogeneity and intrauterine infection was investigated by comparing the quasi species isolated from eight pairs of HBsAg-positive mothers and their neonates, who were infected intrauterinely with HBV, with clones from eight HBsAg-positive mothers whose neonates were not infected with HBV. The proportion of clones with specific mutations was compared among different subject groups, and phylogenetic analysis was performed to evaluate the significance of specific mutations. It was observed that the core promoter with conserved major functional regions and conserved hepatitis B e antigen (HBeAg) might be beneficial to HBV maternal-fetal transmission. Particularly, A1762T/G1764A mutations seemed to be disadvantageous for fetal infection. It was also shown that amino acid substitutions located in the immune epitopes of HBsAg were strongly associated with intrauterine HBV transmission. The clones with mutations such as amino acid P110S in preS1 region, P36L in preS2 region and C107R in S region might infect fetuses more readily. In addition, positively selected site analysis confirmed the above results.

Epidemiological studies of esophageal cancer in the era of genome-wide association studies

Esophageal cancer (EC) caused about 395000 deaths in 2010. China has the most cases of EC and EC is the fourth leading cause of cancer death in China. Esophageal squamous cell carcinoma (ESCC) is the predominant histologic type (90%-95%), while the incidence of esophageal adenocarcinoma (EAC) remains extremely low in China. Traditional epidemiological studies have revealed that environmental carcinogens are risk factors for EC. Molecular epidemiological studies revealed that susceptibility to EC is influenced by both environmental and genetic risk factors. Of all the risk factors for EC, some are associated with the risk of ESCC and others with the risk of EAC. However, the details and mechanisms of risk factors involved in the process for EC are unclear. The advanced methods and techniques used in human genome studies bring a great opportunity for researchers to explore and identify the details of those risk factors or susceptibility genes involved in the process of EC. Human genome epidemiology is a new branch of epidemiology, which leads the epidemiology study from the molecular epidemiology era to the era of genome wide association studies (GWAS). Here we review the epidemiological studies of EC (especially ESCC) in the era of GWAS, and provide an overview of the general risk factors and those genomic variants (genes, SNPs, miRNAs, proteins) involved in the process of ESCC.

Epidemiology of Hepatitis C Virus Infection in Highly Endemic HBV Areas in China

Background Wuwei City has the highest prevalence of hepatitis B virus (HBV) in China. From 2007 to 2011, the average reported incidence rate of hepatitis B was 634.56/100,000 people. However, studies assessing the epidemic features and risk factors of HCV in the general population of Wuwei City are limited. Methods A total of 7189 people were interviewed and screened for HCV antibodies. HCV RNA and HCV genotypes were analyzed by PCR. Relevant information was obtained from the general population using a standardized questionnaire, and association and logistic regression analyses were conducted. Results The anti-HCV prevalence was 1.64% (118/7189), and HCV-RNA was detected in 37.29% (44/118) of the anti-HCV positive samples. The current HCV infection rate was 0.61% (44/7189) in the Wuwei general population. Hepatitis C infection rate was generally higher in the plains regions (χ2 = 27.54,P<0.05), and the most predominant HCV genotypes were 2a (59.1%) and 1b (34.1%). The concurrent HCV and HBV infection rate was 1.37%, and a history of blood transfusion (OR = 17.9, 95% CI: 6.1 to 52.6, p<0.001) was an independent risk factor for HCV positivity. Conclusions Although Wuwei is a highly endemic area for HBV, the anti-HCV positive rate in the general population is low. More than one-third of HCV-infected people were unaware of their infection; this may become an important risk factor for hepatitis C prevalence in the general population. Maintaining blood safety is important in order to help reduce the burden of HCV infection in developing regions of China.

Risk factors for multiple myeloma: A hospital-based case–control study in Northwest China

BACKGROUND The distinctive racial/ethnic and geographic distribution of multiple myeloma (MM) suggests that both family history and environmental factors may contribute to its development. METHODS A hospital-based case-control study consisting of 220 confirmed MM cases and 220 individually matched patient controls, by sex, age and hospital was carried out at 5 major hospitals in Northwest China. A questionnaire was used to obtain information on demographics, family history, and the frequency of food items consumed. RESULTS Based on multivariate analysis, a significant association between the risk of MM and family history of cancers in first degree relatives was observed (OR=4.03, 95% CI: 2.50-6.52). Fried food, cured/smoked food, black tea, and fish were not significantly associated with the risk of MM. Intake of shallot and garlic (OR=0.60, 95% CI: 0.43-0.85), soy food (OR=0.52, 95% CI: 0.36-0.75) and green tea (OR=0.38, 95% CI: 0.27-0.53) was significantly associated with a reduced risk of MM. In contrast, intake of brined vegetables and pickle was significantly associated with an increased risk (OR=2.03, 95% CI: 1.41-2.93). A more than multiplicative interaction on the decreased risk of MM was found between shallot/garlic and soy food. CONCLUSION Our study in Northwest China found an increased risk of MM with a family history of cancer, a diet characterized by low consumption of garlic, green tea and soy foods, and high consumption of pickled vegetables. The effect of green tea in reducing the risk of MM is an interesting new finding which should be further confirmed.

Maternal hepatitis B virus (HBV) DNA positivity and sexual intercourse are associated with HBV intrauterine transmission in China: A prospective case–control study

Background and Aim:  Hepatitis B virus (HBV) intrauterine transmission from infected mothers contributes significantly to the persistence of the high number of HBV carriers. The aim of this study was to identify potential risk factors for HBV intrauterine transmission.

A Population-Based Study Examining Hepatitis B Virus Infection and Immunization Rates in Northwest China

Background and Aim Current baseline data regarding the prevalence of hepatitis B virus (HBV) infections and the immune status in hyperendemic areas is necessary in evaluating the effectiveness of ongoing HBV prevention and control programs in northwest China. This study aims to determine the prevalence of chronic HBV infections, past exposure rates, and immune response profiles in Wuwei City, northwest China in 2010. Methods Cross-sectional household survey representative of the Wuwei City population. 28,579 participants were interviewed in the seroepidemiological survey ≥1 year of age. House to house screening was conducted using a standard questionnaire. All serum samples were screened by enzyme-linked immunoassays for the presence of hepatitis B surface antigen, antibodies against HBV surface antigen, and antibodies to the hepatitis B core antigen. Results Among individuals ≥1 year of age, 7.2% (95%CI: 6.3–8.1%) had chronic HBV infections, 43.9% (CI: 40.4–47.4%) had been exposed to HBV, and 23.49% (CI: 21.6–25.3%) had vaccine-induced immunity. Multi-factor weighted logistic regression analysis showed that having household contact with HBV carriers (OR = 2.6, 95%CI: 2.3–3.0) and beauty treatments in public places (OR = 1.2, 95%CI: 1.1–1.3) were the risk factors of HBV infection in whole population. Having household contact with HBV carriers (OR = 3.8, 95% CI: 2.2–6.5) and lack of hepatitis vaccination (OR = 2.0, 95% CI: 1.4–3.3) were the risk factors for HBV infection in children aged 1–14 years. Conclusions Hepatitis B infection remains a serious public health problem in northwest China. Having household contact with HBV carriers and beauty treatments in public places represented HBV infection risk factors. Hepatitis B vaccine immunization strategies need further improvement, particularly by targeting the immunization of rural migrant workers.

Establishment and characterization of a spontaneously immortalized trophoblast cell line (HPT-8) and its hepatitis B virus-expressing clone

BACKGROUND Most trophoblast cell lines currently available to study vertical transmission of hepatitis B virus (HBV) are immortalized by viral transformation. Our goal was to establish and characterize a spontaneously immortalized human first-trimester trophoblast cell line and its HBV-expressing clone. METHODS Chorionic villi of Asian human first-trimester placentae were digested with trypsin and collagenase I to obtain the primary trophoblast cell culture. A spontaneously immortalized trophoblast cell line (HPT-8) was analyzed by scanning and transmission electron microscopy, cell cycle analysis, immunohistochemistry and immunofluorescence. HPT-8 cells were stably transfected with the adr subtype of HBV (HPT-8-HBV) and characterized by PCR and enzyme-linked immunosorbent assay. RESULTS We obtained a clonal derivative of a spontaneously immortalized primary cell clone (HPT-8). HPT-8 cells were epithelioid and polygonal, and formed multinucleate, giant cells. They exhibited microvilli, distinct desmosomes between adjacent cells, abundant endoplasm, lipid inclusions and glycogen granules, which are all characteristic of cytotrophoblasts. HPT-8 cells expressed cytokeratin 7, cytokeratin 18, vimentin, cluster of differentiation antigen 9, epidermal growth factor receptor, stromal cell-derived factor 1 and placental alkaline phosphatase. They secreted prolactin, estradiol, progesterone and hCG, and were positive for HLA-G, a marker of extravillous trophoblasts. HPT-8-HBV cells were positive for HBV relaxed-circular, covalently closed circular DNA and pre-S sequence. HPT-8-HBV cells also produced and secreted HBV surface antigen and HBV e antigen. CONCLUSIONS We established a trophoblast cell line, HPT-8 and its HBV-expressing clone which could be valuable in exploring the mechanism of HBV viral integration in human trophoblasts during intrauterine infection.