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 therapeutic effects of entecavir (ETV) and interferon- (IFN-) treatments for 48 weeks for chronic hepatitis B (CHB) in patients with different baseline alanine aminotransferase (ALT) levels. METHODS: We retrospectively analyzed the data of 369 CHB patients receiving ETV and IFN- treatments for 48 weeks. We compared the virological response rates, HBsAg clearance, and HBsAg reduction between the patients receiving ETV and IFN- treatments with different baseline ALT levels[≤ 5×upper limits of normal (ULN) level (subgroup 1), 5-10×ULN (subgroup 2), and > 10× ULN (subgroup 3)]. RESULTS: In patients receiving ETV treatment, the virological response rate was 83.3% in subgroup 1, 91.4% in subgroup 2, and 95.5% in subgroup 3, as compared with 19.7%, 40%, and 42.9% in the 3 subgroups with IFN- treatment, respectively, showing significantly differences both among different subgroups with the same treatment and between the same subgroup with different treatments ( < 0.05). HBeAg clearance rates in the 3 subgroups were 8.3%, 16.7% and 35.5% in patients with ETV treatment and were 1.8%, 41.9%, and 38.1% in patients with IFN- treatment, respectively, showing significant differences among the 3 subgroups with the same treatment ( < 0.05); in the same subgroups with different treatments, the rates differed significantly only between subgroups 2 ( < 0.05). In ETV group, the rate of HBsAg reduction to below 200 IU/ml was 2.5% in subgroup 1 and 13.8% in subgroup 2, showing no significant difference between the two subgroups; in IFN- group, the rates were also similar between subgroups 1 and 2 (30.6% 33.3%, > 0.05); but the rates differed significantly between the same subgroups with different treatments ( < 0.05). CONCLUSIONS In all the subgroups with different baseline ALT levels, ETV treatment for 48 weeks results in significantly higher virological response rates than IFN- treatment in patients with CHB. In patients with a baseline ALT of 5-10 ×ULN, IFN- can result in a higher HBeAg clearance rate than ETV. In patients with comparable baseline ALT level, IFN- more effectively reduces HBsAg level than ETV. The patients with a relatively high baseline ALT level (> 5 × ULN) show better responses to both ETV and IFN- treatment than those with ALT level below 5×ULN. We thus recommend IFN- for patients with a baseline ALT of 5-10×ULN and ETV for patients with a baseline ALT either below 5 × ULN or beyond 10×ULN.
Alanine Transaminase ; blood ; Antiviral Agents ; therapeutic use ; DNA, Viral ; Guanine ; analogs & derivatives ; therapeutic use ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; immunology ; Hepatitis B, Chronic ; drug therapy ; enzymology ; immunology ; virology ; Humans ; Interferon-alpha ; therapeutic use ; Retrospective Studies ; Time Factors ; Treatment Outcome ; Viral Load ; drug effects

Background: Cytokines play an important role in occurrence and recovery of hepatitis B virus (HBV) infection. The aim of this study was to investigate the changes of cytokines concentration and its correlation to alanine aminotransferase (ALT), HBV deoxyribonucleic acid (HBV-DNA), hepatitis B envelope antigen (HBeAg), and HBV surface antigen (HBsAg) in the development of chronic hepatitis B (CHB). Methods: Thirteen healthy individuals (HI), 30 chronic HBV-infected patients in immune tolerant (IT) phase, and 55 CHB patients were enrolled between August 2015 and May 2017. The peripheral blood samples were collected from all individuals. The levels of interferon (IFN)-α2, interleukin (IL)-10, transforming growth factor (TGF)-β1, HBV-DNA, HBsAg, and HBeAg and liver function were measured. The quantitative determinations of cytokines levels, including IFN-α2, IL-10, and TGF-β1 were performed using Luminex multiplex technology. The correlation of cytokines to ALT, HBV-DNA, HBsAg, and HBeAg was analyzed by linear regression analysis. Results: IFN-α2 levels were similar between HI and IT groups (15.35 [5.70, 67.65] pg/ml vs. 15.24 [4.07, 30.73] pg/ml, Z = -0.610, P = 0.542), while it elevated significantly in CHB group (35.29 [15.94, 70.15] pg/ml vs. 15.24 [4.07, 30.73] pg/ml; Z = -2.522, P = 0.012). Compared with HI group (3.73 [2.98, 11.92] pg/ml), IL-10 concentrations in IT group (5.02 [2.98, 10.11] pg/ml), and CHB group (7.48 [3.10, 18.00] pg/ml) slightly increased (χ = 2.015, P = 0.365), and there was no significant difference between IT and CHB group (Z = -1.419, P = 0.156). The TGF-β1 levels among HI (3.59 ± 0.20 pg/ml), IT (3.62 ± 0.55 pg/ml), and CHB groups (3.64 ± 0.30 pg/ml) were similar (χ = 2.739, P = 0.254). In all chronic HBV-infected patients (including patients in IT and CHB groups), the elevation of IFN-α2 level was significantly associated with ALT level (β= 0.389, t = 2.423, P = 0.018), and was also negatively correlated to HBV-DNA load (β = -0.358, t = -2.308, P = 0.024), HBsAg (β = -0.359, t = -2.288, P = 0.025), and HBeAg contents (β = -0.355, t = -2.258, P = 0.027). However, when both ALT level and cytokines were included as independent variable, HBV-DNA load, HBsAg, and HBeAg contents were only correlated to ALT level (β = -0.459, t = -4.225, P = 0.000; β = -0.616, t = -6.334, P = 0.000; and β = -0.290, t = -2.433, P = 0.018; respectively). Conclusions IFN-α2 elevation was associated with ALT level in patients with chronic HBV infection. However, in CHB patients, only ALT level was correlated to HBV-DNA, HBsAg and HBeAg contents.
Adult ; Alanine Transaminase ; blood ; Antigens, Surface ; Case-Control Studies ; Cytokines ; blood ; DNA, Viral ; Female ; Hepatitis B ; Hepatitis B Surface Antigens ; analysis ; Hepatitis B e Antigens ; Hepatitis B virus ; Hepatitis B, Chronic ; blood ; immunology ; Humans ; Male ; Young Adult

<b>INTRODUCTIONb>In 2006, Singapore adopted the universal hepatitis B immunoglobulin (HBIg) policy. Since then, all infants of hepatitis B surface antigen (HBsAg)-positive mothers receive HBIg, irrespective of maternal hepatitis B e antigen (HBeAg) status. However, the benefits of HBIg for infants of HBeAg-negative mothers are unclear. We compared the vertical transmission rates among children of HBeAg-negative mothers who were given HBIg versus a retrospective cohort who were not given HBIg, to determine its protective effect.

<b>METHODSb>This observational study involved pregnant HBsAg-positive women seen at National University Hospital, Singapore, between June 2009 and December 2013. If the infants of these mothers completed the recommended vaccination schedule, they were recruited into the study, along with their older siblings. Serological testing for the children was performed three months after completion of the last dose of vaccine, and hepatitis B virus (HBV) surface gene sequencing was carried out if HBV DNA was detected.

<b>RESULTSb>A total of 111 infants and 47 siblings were recruited. 2 (1.5%) children were found to have vertical transmission despite receiving HBIg, while no incidences of vertical transmission were found among the historical controls who did not receive HBIg (p = 1.00).

<b>CONCLUSIONb>The overall effectiveness of the hepatitis B vaccination programme for children of HBsAg-positive mothers was high, regardless of HBIg administration. The addition of HBIg did not appear to confer additional benefits, in terms of vertical transmission rate, among infants born to HBeAg-negative mothers.

Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Hepatitis B ; immunology ; prevention & control ; Hepatitis B Surface Antigens ; blood ; Hepatitis B Vaccines ; administration & dosage ; Hepatitis B virus ; Humans ; Immunoglobulins ; immunology ; Infant ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; prevention & control ; Male ; Mutation ; Pregnancy ; Pregnancy Complications, Infectious ; virology ; Retrospective Studies ; Siblings

<b>OBJECTIVEb>To examine the influence of three-booster-doses hepatitis B vaccines on children with normal and high antibody response to primary vaccination.

<b>METHODSb>Antibody against hepatitis B surface antigen (anti-HBs) were detected after primary vaccination and children with normal or high response to hepatitis B primary vaccination at infancy, were identified. Children who were given three booster doses were selected to form the booster group and who were given no booster dose were 1∶1 matched with the same gender and residence to form the control group. Blood samples were obtained from all the participants and tested for anti-HBs and anti-HBc, 5 years after the primary vaccination.

<b>RESULTSb>The positive rates of anti-HBs response to primary vaccination were 97.39% (224/230, 95% CI: 94.41%-99.04%) in the booster group and 53.91% (124/230, 95% CI: 47.24%-60.48%) in the control group (P<0.05), 5 years after the primary vaccination. Geometric mean concentration (GMC) of anti-HBs were 1 140.02 (887.46-1 464.46) mIU/ml in the booster group and 11.53 (8.73-15.23) mIU/ml in the control group (P<0.05). The prevalence rates of breakthrough HBV infection were 0.87% (2/230) in the booster group and 2.17%(5/230) in the control group (P>0.05). RESULTS from the multivariable analysis showed that the booster doses (OR=38.75, 95%CI: 16.23-92.54) and the level of anti-HBs after the primary vaccination (OR =3.06, 95%CI:1.51-6.17) were independently associated with the positive rates of anti-HBs, 5 years after the primary vaccination (P<0.05).

<b>CONCLUSIONb>Programs with three booster doses to children that showing normal and high antibody response to primary vaccination could improve the persistence of anti-HBs but possibly would not be able to prevent the HBV infection.

Antibody Formation ; Case-Control Studies ; Child ; Hepatitis B ; prevention & control ; Hepatitis B Antibodies ; blood ; immunology ; Hepatitis B Surface Antigens ; immunology ; Hepatitis B Vaccines ; administration & dosage ; immunology ; Hepatitis B virus ; Humans ; Immunization, Secondary ; Infant ; Prevalence ; Treatment Outcome ; Vaccination

<b>OBJECTIVEb>To analyze the characteristics of lymphocyte phenotypes in hepatitis B virus (HBV) transgenic mice and the effect of exogenous interferon-α on virological profiles and lymphocytes phenotypes of the mice.

<b>METHODSb>HBV transgenic mice and wild-type (WT) mice were examined for serum levels of HBsAg, HBcAb, IL-21, and IL-6 using ELISA. The frequencies of CD4(+)T and CD19(+)B cells separated from the liver, spleen, and peripheral blood were detected by flow cytometry. Nine HBV transgenic mice were injected subcutaneously with recombinant mouse interferon alpha (rmIFN-α) and another 9 transgenic mice were injected with PBS, and their HBsAg, HBV DNA, IL-6, and IL-21 levels and frequencies of peripheral blood CD4(+)T and CD19(+)B cells were detected.

<b>RESULTSb>HBV transgenic mice showed a high level of HBsAg with a detectable level of HBcAb and significantly increased serum levels of IL-21 and IL-6 as compared with WT mice (P<0.05). The transgenic mice had a significantly lower frequency of CD4(+) T cells in the peripheral blood, liver and spleen (P<0.05) but a significantly higher frequency of CD19(+) B cells in the liver (P<0.05). An inverse correlation between intrahepatic CD4(+) T cell frequency and serum HBsAg level while a positive correlation between intrahepatic CD19(+) B cell frequency and HBcAb level were found in HBV transgenic mice. Administration of rmIFN-α significantly increased the frequencies of CD4(+) T and CD19(+) B cells in the peripheral blood and the serum level of IL-6 in HBV transgenic mice (P<0.05).

<b>CONCLUSIONb>HBV transgenic mice have lymphocyte subset dysregulation and exogenous interferon-α can modulate the immune function of the mice by regulating the frequencies of lymphocyte subsets.

Animals ; Antiviral Agents ; pharmacology ; B-Lymphocytes ; drug effects ; DNA, Viral ; blood ; Hepatitis B ; drug therapy ; immunology ; Hepatitis B Antibodies ; blood ; Hepatitis B Surface Antigens ; blood ; Hepatitis B virus ; Interferon-alpha ; pharmacology ; Interleukin-6 ; blood ; Interleukins ; blood ; Liver ; immunology ; Lymphocyte Subsets ; cytology ; drug effects ; Mice ; Mice, Transgenic ; Phenotype ; T-Lymphocytes ; drug effects

<b>OBJECTIVEb>To analyze the development of liver damage and reactivation of hepatitis B virus (HBV) during the treatment of extremely severe burn injury in HBsAg positive patients, in order to provide reference for prevention and treatment of liver damage in patients with HBV infection after extremely severe burn.

<b>METHODSb>Medical records of 54 HBsAg positive patients after extremely severe burn injury admitted from January 2004 to December 2014 were retrospectively analyzed. Development of liver damage and HBV reactivation of these patients during the treatment were analyzed according to the classification of their gender, results of hepatitis B e antigen (HBeAg) and HBV DNA examinations on admission, and development of sepsis in the process of treatment. Data were processed with chi-square test.

<b>RESULTSb>(1) The incidence of liver damage in the process of treatment of these patients was 85.2% (46/54). Among all the patients, the proportion of liver damage was 35/38 in male, which was significantly higher than that in female (11/16, χ² = 4.867, P<0.05). Liver damage was found in all of 26 patients who were HBeAg positive on admission, 34 patients who were HBV DNA positive on admission, and 36 patients who developed sepsis in the process of treatment; the proportions were significantly higher than those in patients who were HBeAg negative on admission (20/28), patients who were HBV DNA negative on admission (12/20), and patients who did not develop sepsis in the process of treatment (10/18), with χ² values respectively 11.801, 18.384, and 20.574, P values below 0.01. (2) The incidence of HBV reactivation in these patients was 29.6% (16/54). Among all the patients, the proportion of HBV reactivation was 13/38 in male and 3/16 in female, with no statistically significant difference between them (χ² = 0.656, P>0.05). The proportions of HBV reactivation in patients who were HBeAg positive on admission, patients who were HBV DNA positive on admission, and patients who developed sepsis in the process of treatment were respectively 13/26, 16/34, and 15/36, and they were significantly higher than those in patients who were HBeAg negative on admission (3/28), patients who were HBV DNA negative on admission (0/20), and patients who did not develop sepsis in the process of treatment (1/18), with χ² values respectively 9.979, 18.615, and 5.873, P<0.05 or P<0.01.

<b>CONCLUSIONSb>Patients who are HBsAg positive, HBeAg positive, HBV DNA positive on admission, and develop sepsis in the process of treatment of extremely severe burn injury are more likely to develop liver damage and HBV reactivation. It is necessary to dynamically monitor the changes in HBV DNA and liver function, in order to identity the reactivation of virus.

Alanine Transaminase ; blood ; Burns ; complications ; drug therapy ; Chemical and Drug Induced Liver Injury ; DNA, Viral ; Female ; Hepatitis Antibodies ; blood ; Hepatitis B ; drug therapy ; epidemiology ; virology ; Hepatitis B Surface Antigens ; blood ; immunology ; Hepatitis B virus ; drug effects ; immunology ; isolation & purification ; Hepatitis B, Chronic ; blood ; pathology ; virology ; Humans ; Incidence ; Liver ; pathology ; Male ; Retrospective Studies

BACKGROUND/AIMS: Quantification of hepatitis B surface antigen (HBsAg) is an emerging serologic test and may be useful for identifying treatment strategies for chronic hepatitis B (CHB). This study aimed to evaluate HBsAg titers during the natural course of CHB and identify correlations between HBsAg titers and hepatitis B virus (HBV) DNA concentrations across different CHB phases measured using an immunoradiometric assay (IRMA). METHODS: CHB phases were defined on the basis of HBV DNA concentrations, the presence of hepatitis B e antigen/antibody (HBeAg/Ab) and serum alanine aminotransferase levels. Serum HBsAg titers and paired HBV DNA concentrations in the different phases of CHB were compared using 627 serum samples. RESULTS: Mean HBsAg titers were significantly higher in the immunotolerant (IT) phase and immunoreactive (IR) HBeAg-positive phase than in the low-replicative (LR) and HBeAg-negative CHB (ENH) states. The correlation between HBsAg titers and HBV DNA concentrations was modest in the IT (n=36, r=0.804, p<0.001) and IR (n=48, r=0.773, p<0.001) phases, and it was poor in the LR state (n=116, r=0.289, p=0.002); however, no significant correlation was observed in the ENH state (n=67, r=0.146, p=0.237) or in the oral nucleos(t)ide analogue-treated group (n=267). CONCLUSIONS: HBsAg quantification using IRMA might be useful for discriminating different CHB phases and different stages of chronic liver disease.
Adult ; Alanine Transaminase/blood ; Biomarkers/blood ; DNA, Viral/*blood ; Disease Progression ; Female ; Hepatitis B Surface Antigens/*blood ; Hepatitis B e Antigens/blood ; Hepatitis B virus/*genetics/immunology ; Hepatitis B, Chronic/*immunology ; Humans ; *Immunoradiometric Assay ; Male ; Middle Aged ; Seoul ; Viral Load ; Virus Replication

<b>OBJECTIVEb>To access the antibody persistence 24-month after revaccination with 3-dose of hepatitis B vaccine (HepB) among non-response adults.

<b>METHODSb>A total of 24 237 healthy adults who had no histories of hepatitis B infection and hepatitis B vaccination, resided in the local area for more than six months and were aged 18-49 years were selected from 79 villages of Zhangqiu county, Shandong province, China in 2009. Blood samples were obtained and hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected using ELISA method. A total of 11 590 persons who were negative for all of these indicators were divided into four groups by cluster sampling methods. Each group was vaccinated with one of the following four types of HepB at 0-, 1-, 6-months schedule: 20 µg HepB derived in Saccharomyces Cerevisiae (HepB-SC), 20 µg HepB derived in Chinese hamster ovary cell (HepB-CHO), 10 µg HepB-SC and 10 µg HepB derived in Hansenula Polymorpha (HepB-HP). Blood samples were collected one month after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). The non-responders were revaccinated with three doses of HepB at 0-, 1-, 6-months schedule and the type of HepB was the same as which was used for primary immunization. Blood samples were collected one month (T1) and two years (T24) after revaccination and anti-HBs, antibody against hepatitis B core antigen (anti-HBc) and hepatitis B surface angtigen (HBsAg) (if anti-HBs < 10 mU/ml) were detected by CMIA. χ(2) test was used to compared age, gender and body mass index (BMI) between different groups and the anti-HBs positive rate at T1 and T24; analysis of variance (ANOVA) was used to compare the geometric mean concentration (GMC) of anti-HBs between difference groups. The risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple logistic regression analysis and multifactor linear regression model analysis respectively.

<b>RESULTSb>A total of 900 non-responders were identified and 71.7% (645/900) of them completed three-dose revaccination and blood collection after revaccination. 467 (72.4%) non-responsive adults were followed up at T24. The anti-HBs positive rate decreased from 85.65% (95% CI: 82.14%-88.71%) at T1 to 60.60% (95% CI: 56.01%-65.06%) at T24 and the corresponding GMC decreased from 175.62 (95% CI: 139.03-221.84) mU/ml to 21.43 (95% CI: 17.62-26.06) mU/ml. Multivariate analysis showed that positive rate of anti-HBs at T24 was associated with gender, HepB type for revaccination and anti-HBs level at T1, but only anti-HBs level at T1 was associated with the anti-HBs titer at T24. No subject showed HBsAg seroconversion and anti-HBc conversion rate was 3.64% (17/467) at T24.

<b>CONCLUSIONb>Anti-HBs titer decreases rapidly two years after HepB revaccination among non-responsive adults, but more than half non-responderd still kept anti-HBs above protective level. The immunity durability after revaccination was associated with gender, HepB type for revaccination and anti-HBs titer one month after revaccination.

Adolescent ; Adult ; Animals ; Body Mass Index ; CHO Cells ; China ; Cricetinae ; Cricetulus ; Enzyme-Linked Immunosorbent Assay ; Female ; Follow-Up Studies ; Hepatitis B ; prevention & control ; Hepatitis B Antibodies ; blood ; Hepatitis B Core Antigens ; immunology ; Hepatitis B Surface Antigens ; immunology ; Hepatitis B Vaccines ; administration & dosage ; classification ; Humans ; Immunization, Secondary ; Male ; Middle Aged ; Multivariate Analysis ; Pichia ; Risk Factors ; Saccharomyces cerevisiae ; Seroconversion ; Vaccination ; Young Adult