OBJECTIVE: To analyze the relationship between miR451a and occult hepatitis B virus infection (OBI) in voluntary blood donors, and to provide ideas for the identification of OBI. METHODS: A total of 125 003 blood samples were collected from voluntary blood donors in our center from January 2022 to June 2023, and OBI infection was detected by blood screening. At the same time, 40 HBsAg double reagent reactive samples (S/CO>3.0) were selected as the positive control group, and 40 healthy blood donors were selected as the negative control group (normal group). The plasma miR451a level was detected, and the serum indexes of total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST). The relationship between miR451a and OBI were analyzed. RESULTS: 54 out of 125 003 blood samples were diagnosed as OBI, and the OBI infection rate was 0.043% (54/125 003). Compared with the normal group, the relative expression of plasma miR451a in the OBI group and the positive control group was down-regulated (P < 0.05), but there was no significant difference in the relative expression of plasma miR451a between the OBI group and the positive control group (P >0.05). The HBV DNA load, TBil, ALT and AST levels in the positive control group were higher than those in the OBI group and the normal group (P < 0.05). There was no significant difference in plasma TBil, ALT and AST levels between OBI group and normal group (P >0.05). Logistic regression analysis and receiver operating curve (ROC) showed that plasma miR451a could distinguish OBI group from healthy group, and the area under the curve (AUC) was 0.904 (95%CI : 0.829-0.978). However, plasma miR451a was difficult to distinguish between OBI and HBsAg responders. CONCLUSION Plasma miR451a can be used as a potential biomarker for HBV infection, and can be used to identify OBI in HBsAg non-reactive blood donors.
Humans ; MicroRNAs/blood* ; Blood Donors ; Hepatitis B/blood* ; Hepatitis B virus ; Alanine Transaminase/blood* ; Aspartate Aminotransferases/blood* ; Female ; Male ; Adult ; Hepatitis B Surface Antigens/blood*

OBJECTIVE: To investigate the pattern of hepatitis B virus (HBV) infection and the prevalence of hepatitis D virus (HDV) infection among voluntary blood donors who tested reactive for HBV in Wuhan, and to provide data support for the prevention and treatment of HBV and HDV infections. METHODS: Electrochemiluminescence (ECL) method was used to detect hepatitis B serological markers in the samples with HBsAg and/or HBV DNA reactivity, and the HBV infection in different groups was statistically analyzed. The HDV IgM and IgG antibodies were screened by ELISA, and the prevalence of HDV infection in the retained samples was analyzed. RESULTS: In 351 ELISA and/or nucleic acid test (NAT) reactive samples, the serological tests for hepatitis B revealed that 4 cases (1.1%) were positive for HBsAg, HBeAg, and anti-HBc, 182 cases (51.9%) were positive for HBsAg, anti-HBe, and anti-HBc, and 55 cases (15.7%) were negative for HBsAg but positive for anti-HBc. Among them, the HBsAg ELISA dual reagent reactive group (HBsAg R&R group) and the HBsAg ELISA single reagent reactive/HBV DNA reactive group (HBsAg R&NR/HBV DNA R group) had the highest rates of HBsAg(+), anti-HBe(+), and anti-HBc(+), accounting for more than 90% and 65%, respectively, followed by low activity of HBV acute infection or chronic carriers, accounting for about 5% and 20%, respectively. In the HBsAg R&NR/HBV DNA NR group, the combined proportion of individuals with anti-HBs single positive and all hepatitis B serological markers negative accounted for 78%, and those who were HBsAg negative but anti-HBc positive accounted for approximately 20%. In the HBsAg NR&NR/HBV DNA R group, there was nearly 9% of HBsAg(+), anti-HBe(+), and anti-HBc(+), the remaining were all HBsAg negative but anti-HBc positive, with a 100% anti-HBc positivity rate in this group. No HDV IgM or IgG antibodies were detected in the retained samples. CONCLUSION Blood donors with HBV-reactive results in blood screening exhibit multiple patterns of infection indicators. The prevalence rate of HDV infection among blood donors in Wuhan is extremely low. However, the risk of asymptomatic occult hepatitis B infection (OBI) blood donors being co-infected with HDV should not be overlooked in areas with high prevalence of HBV.
Humans ; Blood Donors ; Hepatitis B/blood* ; China/epidemiology* ; Adult ; Male ; Female ; Hepatitis D/epidemiology* ; Middle Aged ; Hepatitis B virus/immunology* ; Hepatitis B Antibodies/blood* ; Young Adult ; DNA, Viral/blood* ; Hepatitis B Surface Antigens/blood* ; Prevalence ; Adolescent

Hepatitis B is a global public health concern. Inducing hepatitis B surface antibody (HBsAb) through vaccination is a crucial preventive strategy. However, individuals show varying immune responses to the hepatitis B vaccine. Based on HBsAb levels, individuals can be categorized as high responders, low responders, or non-responders. T cells and their subsets play critical roles in modulating this response, and the composition of the T cell receptor (TCR) repertoire also influences immune responsiveness. Investigating the characteristics of T cells, their subsets, and TCR repertoires in individuals with differential responses post-vaccination may provide theoretical guidance for optimizing vaccine design and immunization strategies.
Humans ; Hepatitis B Vaccines/immunology* ; Hepatitis B/immunology* ; Vaccination ; Hepatitis B Antibodies/blood* ; T-Lymphocytes/immunology* ; Receptors, Antigen, T-Cell/immunology* ; Hepatitis B Surface Antigens/immunology* ; T-Lymphocyte Subsets/immunology*

OBJECTIVE: To evaluate the risk of reentry in HBV reactive blood donors and feasibility of HBV reentry strategy. METHODS: HBsAg⁺ or HBV DNA⁺ donors who had been quarantined for more than 6 months in Jiangsu Province could propose for reentry application. Blood samples were routinely screened by dual-ELISA for HBsAg, anti-HCV, HIV Ab/Ag, and anti- Treponema pallidum and those non-reactive ones were tested by minipool nucleic acid testing (NAT) for three times. To identify occult HBV donors, samples of NAT non-reactive were further tested by electrochemiluminescence immunoassay (ECLIA) for HBV seromarkers (including HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb). Donors of only 4 ECLIA patterns were accepted to reentry, including all 5 HBV seromarkers negative, anti-HBs only but having history of hepatitis B vaccine injection, HBcAb only, HBsAb⁺ / HBcAb⁺ with HBsAb more than 200 IU/L. Additionally, the detection rate of HBV infection was compared between routine screening mode and ECLIA, as well as the reentry qualified rate of HBsAg⁺ and HBV DNA⁺ blood donors. RESULTS: From Oct. 2016 to Aug. 2019, a total of 737 HBV reactive donors had applied for reentry, including 667 HBsAg⁺ reactive and 70 HBV DNA⁺ reactive donors. Among 3 screening methods, the highest HBV detection rate (43.15%, 318/737) was observed on ECLIA, while only 4.75% (35/737) on ELISA and 3.12% (23/737) on NAT, respectively. Among 4 qualified patterns of HBV serological markers, the highest proportion was found in the all negative group (22.90%, 155/677), followed by the group with HBsAb⁺ only and history of hepatitis B vaccine injection (19.35%, 131/677), and the median concentration of HBsAb was 237.7 IU/L. The unqualified rate of HBV DNA⁺ donors was 82.86%, which was significantly higher than 47.98% of HBsAg⁺ donors. CONCLUSION Routine screening tests merely based on ELISA and NAT could miss occult HBV donors and may not be sufficient for blood safety. HBsAb concentration and vaccine injection history should be included in the evaluation of HBV reactive donors who intend to apply for reentry. There is a relatively larger residual risk of occult HBV infection in blood donors quarantined for HBV DNA reactive.
Blood Donors ; DNA, Viral ; Hepatitis B ; Hepatitis B Surface Antigens ; Hepatitis B virus/genetics* ; Humans

OBJECTIVE: To investigate the status of transfusion-transmissible infection (TTI) among voluntary blood donors in Nanjing in recent five years, in order to provide data support for the recruitment of blood donors and formulation and updating of blood screening strategies. METHODS: HIV/HBV/HCV/TP serological markers were detected by ELISA in 487 120 blood donors in Nanjing from 2016 to 2020. Confirmatory assay was applied in anti-HIV positive samples by Nanjing Municipal Center for Disease Control and Prevention. The prevalence of TTI was calculated and the trend of disease was analyzed under different demographic groups. RESULTS: The total positive rate of TTI in blood donors was 0.49% (2 411/487 120), in which the overall seroprevalence rate of HBsAg, anti-HCV, anti-HIV and anti-TP was 0.23%, 0.09%, 0.01% and 0.16%, respectively. The overall prevalence of HIV and TP remained relatively steady (P>0.05), whereas HBV and HCV decreased year by year (P<0.05). The prevalence of TTI was higher among people with lower education level, high age group and first-time blood donation. CONCLUSION The prevalence of TTI among voluntary blood donors in Nanjing is at a low level from 2016 to 2020, but the risk still exists. The recruitment of regular donors and the improvement of blood screening technology can effectively reduce the risk of TTI.
Blood Donors ; HIV Infections/epidemiology* ; Hepatitis B Surface Antigens ; Humans ; Prevalence ; Seroepidemiologic Studies ; Syphilis ; Volunteers

Hepatitis B virus core protein can self-assemble into icosahedral symmetrical viral-like particles (VLPs) in vitro, and display exogenous sequences repeatedly and densely on the surface. VLPs also have strong immunogenicity and biological activity. When the nanoparticles enter the body, they quickly induce specific humoral and cellular immune responses to exogenous antigens. In this study, we designed an HBc-VLPs that can be coupled with antigens at specific sites, and developed a set of efficient methods to prepare HBc-VLPs. Through site-specific mutation technology, the 80th amino acid of peptide was changed from Ala to Cys, a specific cross-linking site was inserted into the main immunodominant region of HBc-VLPs, and the prokaryotic expression vector pET28a(+)-hbc was constructed. After expression and purification, high purity HBc(A80C) monomer protein was assembled into HBc-VLPs nanoparticles in Phosphate Buffer. The results of particle size analysis show that the average particle size of nanoparticles was 29.8 nm. Transmission electron microscopy (TEM) showed that HBc-VLPs formed spherical particles with a particle size of about 30 nm, and its morphology was similar to that of natural HBV particles. The influenza virus antigen M2e peptide as model antigen was connected to Cys residue of HBc-VLPs by Sulfo-SMCC, an amino sulfhydryl bifunctional cross-linking agent, and M2e-HBc-VLPs model vaccine was prepared. The integrity of HBc-VLPs structure and the correct cross-linking of M2e were verified by cell fluorescence tracing. Animal immune experiments showed that the vaccine can effectively stimulate the production of antigen-specific IgG antibody in mice, which verified the effectiveness of the vaccine carrier HBc-VLPs. This study lays a foundation for the research of HBc-VLPs as vaccine vector, and help to promote the development of HBc-VLPs vaccine and the application of HBc-VLPs in other fields.
Animals ; Hepatitis B Core Antigens ; genetics ; immunology ; Immunity, Cellular ; immunology ; Immunoglobulin G ; blood ; Mice ; Mice, Inbred BALB C ; Vaccines, Virus-Like Particle ; genetics ; immunology

OBJECTIVE: To analyze the reentry situation of HBsAg single reagent reactive blood donors in Anhui province, and to verify the rationality and effectiveness of reentry strategy of blood donors in Anhui province. METHODS: Shielded blood donors who were HBsAg single reagent reactive might voluntarily apply for returning to the team of blood donors after the shield of 6 months. Blood bankstaff that shielded those donors should draw blood and conduct screening tests. Samples from donors who were HBsAg negative should be delivered to Anhui Blood Center to conduct the reentry detections. Shielded blood donors were allowed to return to the team if the results of HBsAg test, neutralization test, HBcAb test and nucleic acid test were negative. RESULTS: 109 person-portions of samples for returning to team from September 2013 to December 2016 were delivered to Anhui Blood Center. After reentry tests, 60 of them were negative, 8 cases were positive, while 41 cases were undetermined, and the qualified rate was 55.05%.25 negative donors were from Hefei, 20 of them donated blood again and were negative. CONCLUSION The shielding and reentry strategy of blood donors with HBsAg single reagent reactive in Anhui province is rational and effective. However, there are still some deficiencies in trace of donors and information transmission, which needs to be further improved.
Blood Donors ; DNA, Viral ; Hepatitis B ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Humans

OBJECTIVE: To explore the reasons causing the false positive of HBsAg single-ELISA-reactive in blood donors of Jiangsu province so as to provide reference data for the return of blood donors. METHODS: Serological test: HBsAg ELISA parallel detection was performed on 319 444 samples of blood donors from 2014 to 2017; the ECLIA was employed to confirm the single-ELISA-reactive (S/CO≥0.5) samples, the nucleic acid test was used to detect the HBV DNA on the all single-ELISA-reactive samples in 6/8 people mixed/single. Reagent evaluation: the Receiver-Operating-Characteristic curve (ROCC) was drawn by the ECLIA/NAT results as the gold standard, and the diagnostic performance of reagents A and B under different cut-off was evaluated. RESULTS: A total of 227 (0.71‰) single-ELISA-reactive samples were detected among 319 444 blood donors, including 39 cases (17.2%) of positive HBsAg and 12 cases (5.3%) of positive HBV DNA; Under the maximum YI, the COI (1.0) employed by the manufacturer recommendation has a better diagnostic value than laboratory COI (0.5), and the capability of reagent A was better than that of reagent B (AUC: 0.661 vs 0.632; Youden: 0.329 vs 0.297), but the specificity of both reagents was restricted (＜60%). Under the maximum YI, the best cut-off value of reagents A and B were 2.4 and 1.4 COI, respectively. Compared with the cut-off value of manufacturer, the sensitivity of reagents A decreased by 33% and the false positive rate decreased by 60% while the sensitivity of reagent B increased by 140% and the false positive rate increased by 36%, respectively. CONCLUSION The false positive of HBsAg single-ELISA-reactive in blood donors is caused by the limited specificity of ELISA reagent and the setting of COI values. According to ROCC maximum YI method, the COI can be set as 2.4 COI and (0.5-1.4) COI for reagent A and B to reduce false positive rate.
Blood Donors ; DNA, Viral ; Enzyme-Linked Immunosorbent Assay ; Hepatitis B ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Humans ; Sensitivity and Specificity

To evaluate the efficacy and safety of Gantaishu Capsules in the treatment of viral B hepatitis. The randomized controlled trials( RCT) retrieved from Cochrane Library,PubMed,Sino Med,CNKI,Wan Fang and VIP were enrolled. The methodology quality of the included studies was evaluated,and a Meta-analysis was performed using Rev Man 5. 3 software. A total of six randomized controlled trials were included. Meta-analysis results showed that the similarities in the negative conversion rate of HBe Ag( RR = 2. 09,95%CI[0. 90,4. 85],P = 0. 09,I2= 0%),the HBV-DNA negative rate( RR = 1. 49,95% CI[0. 56,3. 95],P = 0. 43,I2= 0%) and the changes in ALT levels before and after treatment( RR =-6. 28,95%CI[-72. 83,60. 27],P = 0. 85,I2= 99%),with no statistical difference. In terms of quality of life,Gantaishu Capsules can significantly alleviate the symptoms of hepatitis B patients,with less adverse reactions. Gantaishu Capsules and Dongbao Gantai Tablets were similar in antiviral effect. In this term,Gantaishu Capsules was superior to Dangfei Liganning Capsules. It can significantly alleviate the symptoms of chronic hepatitis B patients,with a good clinical safety.Therefore,it can be applied in the case of syndrome differentiation and treatment. In view of the low quality of the included studies,more high-quality clinical trials were required to confirm its efficacy.
Antiviral Agents ; therapeutic use ; Capsules ; DNA, Viral ; blood ; Drugs, Chinese Herbal ; therapeutic use ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; drug therapy ; Humans ; Quality of Life

OBJECTIVE: To investigate the relationship between maternal peripheral blood mononuclear cells (PBMC) hepatitis B virus (HBV) covalenty closed circular deoxyribonucleic acid (cccDNA) and other HBV serological markers and its effects on HBV intrauterine transmission. METHODS: We enrolled 290 newborns and their hepatitis B surface antigen (HBsAg) positive mothers. HBV cccDNA in PBMC and HBV DNA in serum were detected by a real-time PCR-TaqMan probe while HBV serological markers were detected with an electrochemiluminescence immunoassay. RESULTS: There was a positive correlation between the levels of PBMC HBV cccDNA and serum HBV DNA and HBeAg (r = 0.436 and 0.403, P < 0.001). The detection rate of pattern A ['HBsAg (+), HBeAg (+), and anti-HBc (+)'] was significantly higher in the PBMC HBV cccDNA positive group than in the control group (χ2 = 48.48, P < 0.001). There was a significant association between HBV intrauterine transmission and PBMC HBV cccDNA (χ2 = 9.28, P = 0.002). In the presence of serum HBV DNA, HBeAg, and PBMC HBV cccDNA, the risk of HBV intrauterine transmission was three times higher (OR = 3.69, 95% CI: 1.30-10.42) than that observed in their absence. The risk of HBV intrauterine transmission was the greatest (OR = 5.89, 95% CI: 2.35-14.72) when both PBMC HBV cccDNA and pattern A were present. A Bayesian network model showed that maternal PBMC HBV cccDNA was directly related to HBV intrauterine transmission. CONCLUSION PBMC HBV cccDNA may be a direct risk factor for HBV intrauterine transmission. Our study suggests that serological markers could be combined with PBMC-related markers in prenatal testing.
Adolescent ; Adult ; DNA, Viral ; blood ; Disease Transmission, Infectious ; Female ; Hepatitis B ; congenital ; transmission ; Hepatitis B e Antigens ; blood ; Humans ; Infant, Newborn ; Leukocytes, Mononuclear ; virology ; Male ; Middle Aged ; Young Adult