Decreased placental TLR3 is associated with hepatitis B virus vaccine responsiveness in infants born to HBsAg-positive mothers.

Background: Although hepatitis B vaccination has a significant impact on the reduction hepatitis B virus (HBV) infection, babies born to hepatitis B surface antigen (HBsAg) positive mothers bear a high risk of being poor responsive to the vaccine with unilluminated mechanism. Toll-like receptor 3 (TLR3) plays a vital role in placental immunity, which affects the immune response of these babies. This study investigated the role of placental TLR3 in the immune responses of babies born to HBsAg-positive mothers to the HBV vaccine. Methods: One hundred pairs of HBsAg-positive mothers and their newborns were recruited. Maternal blood samples were collected before delivery, and placental tissues were collected after delivery. Newborns were administered standard passive and active immunoprophylaxis and followed up until the age of 1. Infant blood samples were collected at 1 year of age. Mothers and infants were tested for HBV serological markers and HBV DNA by electrochemiluminescence immunoassay and fluorescence quantitative polymerase chain reaction. respectively. Placental TLR3 was detected by immunohistochemistry and score in a semi-quantitative fashion, circulating cytokines in infants were detected by enzyme-linked immunosorbent assay. Infants with anti-HBs ≥100 and <100 mIU/mL were classified into the high-responsiveness group and the non- or hypo-responsiveness group. Results: The TLR3 protein was expressed in all placentas. Compared with the high-responsiveness group, the expression of TLR3 in the non- or hypo-responsiveness group was significantly decreased (χ2=10.39, P=0.001). A non-conditional logistic regression model showed that the increased expression of placental TLR3 protein decreased the odds of HBV vaccine non- or hypo-responsiveness in the babies of HBsAg-positive mothers [OR =0.25 (95% CI: 0.11-0.58)], and this association remained significant after accounting for maternal factors, such as HBeAg and HBV DNA, as well as infant cytokines, including IL-6, IL-12, TNF-α, IFN-α, and IFN-γ [OR =0.15 (95% CI: 0.05-0.44)]. Conclusions: Decreased placental TLR3 expression is associated with impaired responsiveness to HBV vaccination in babies born to HBsAg-positive mothers.

A cross-sectional survey on the rate of awareness of hepatitis B virus (HBV) infection and the prevention of mother-to-child transmission among hepatitis B surface antigen (HBsAg)-positive pregnant women.

Background: Mother-to-child transmission (MTCT) remains the main transmission route of hepatitis B virus (HBV) in China. Hepatitis B surface antigen (HBsAg) positive pregnant women were the main participants in MTCT of HBV. Nevertheless, little was known about their knowledge and awareness of HBV infection and MTCT. We intended to evaluate their knowledge of HBV infection and MTCT prevention, and to clarify the emphasis of health education to improve the control of MTCT of HBV. Methods: We invited 164 HBsAg-positive pregnant women, who were aged ≥18 years old, had basic literacy skills and visited the Outpatient Clinic of Infectious Disease of the Sun Yat-Sen Memorial Hospital from May 2019 to January 2020, to independently and anonymously complete a self-administered survey regarding their knowledge of HBV infection and MTCT prevention. The correct rate of the questions was calculated and analyzed. A multivariate regression was conducted to identify predictors of HBV and MTCT knowledge and awareness. Results: The average awareness rate of the 164 respondents was 52.56%, among which the awareness rates of basic knowledge and the transmission route of HBV were 80.49% and 53.29%, respectively. The awareness rates of knowledge about the interruption measures of MTCT during pregnancy, delivery, and postpartum were 43.78%, 49.75%, and 31.25%, respectively. The respondents who had a college education level or above, were employed, and had visited the outpatient Department of Infectious Disease before pregnancy had a significantly higher awareness rate. Previous visits to the Department of Infectious Disease were the only influencing factor for the higher awareness rate (OR =3.108, P=0.049). Conclusions: A lack of knowledge about the transmission route and interruption measures of MTCT of HBV is still common among HBsAg-positive pregnant women. Health education should be directed toward HBsAg-positive mothers to further improve the control of HBV infection.

Hepatitis D (DELTA).

The hepatitis D virus (HDV) is unique in animal virology. It is the smallest of human pathogens, re- quires the HBsAg capsid of the hepatitis B virus (HBV) to assembly into infectious virions, and parasitizes the transcriptional machinery of the host. Hepatitis D is ubiquitous but prevalence varies throughout the world. It is the most severe form of chronic viral liver disorder. Vaccination against the HBV has decreased the circulation of HDV in industrialized countries but Hepatitis D remains a significant medical issue in many areas of the developing world.

Impact of hepatitis B surface antigen positive grafts on liver transplantation in patients with benign and malignant liver disease.

Hepatitis B surface antigen (HBsAg) persists after liver transplantation in almost all patients receiving HBsAg-positive grafts. Chronic hepatitis B virus (HBV) infection is one of the main causes of hepatocellular carcinoma (HCC). We aimed to investigate possible interactions between HBsAg-positive donors, HCC, HBV-related transplant indication, and long-term outcomes. This retrospective study enrolled 1176 patients from two centers between January 2015 and May 2019, of which 135 (11.5%) were HBsAg-positive and 1041 (88.5%) were HBsAg-negative donors. Cox regression models were fitted to study the association between variables and patient and graft survival. In univariate and multivariate analyses, the donor HBsAg status was not significantly associated with patient and graft survival in the entire cohort, but there was a significant interaction between HBsAg-positive donors and HCC, independent of HBV-related transplant indication. The cumulative incidence of patient and graft survival was significantly lower in the subgroup of HCC recipients receiving HBsAg-positive grafts, but no significant difference was found in recipients with benign liver disease. In a subgroup analysis of HCC recipients, HBsAg-positive donors were significantly associated with an increased risk of HCC recurrence (hazard ratio: 1.73; 95% confidence interval: 1.20-2.48; p = 0.003) and similar results were obtained after propensity score matching analysis. We showed excellent outcomes of using HBsAg-positive grafts in patients with benign liver disease, regardless of HBV-related transplant indications. However, positive grafts should be used with caution in recipients with HCC, which are associated with an increased risk of HCC recurrence.

Utilization of hepatitis B virus surface antigen positive grafts in liver transplantation: A matched study based on a national registry cohort.

BACKGROUND AND AIM: Donor shortage has become worldwide limitation in liver transplantation (LT). Use of hepatitis B virus surface antigen positive (HBsAg+) donors could be an alternative source of donor organs. This study aims to investigate the safety and efficacy of LT using HBsAg+ liver grafts and associated long-term outcome. METHODS: This was a retrospective study of adults LT registered in the database of the China Liver Transplant Registry between January 2015 and September 2018. By propensity score matching (1:1), 503 eligible patients who received HBsAg+ liver grafts were compared with 503 matched patients who received HBsAg- liver grafts. RESULTS: The 1-, 3-, and 5-year patient survival rates were 81.52%, 72.04%, and 66.65% in HBsAg+ donor group, which were comparable with 83.93%, 77.27%, and 65.73% in HBsAg- donor group (P = 0.222). The 1-, 3-, and 5-year graft survival rates were also comparable between the two groups (81.49%, 71.45%, and 67.26% vs 83.62%, 77.11%, and 65.81%, respectively, P = 0.243). Most main complications were not increased in HBsAg+ donor group except for the retaining of HBsAg positivity after LT. Furthermore, transplanting HBsAg+ liver grafts did not result in inferior outcomes either in HBsAg+ or HBsAg- recipients. The risk of tumor recurrence after LT was not increased in hepatocellular carcinoma patients. CONCLUSIONS: The outcomes of using HBsAg+ liver grafts were comparable with those of HBsAg- liver grafts. Our study provided strong evidence for the safe use of HBsAg+ grafts in LT to expand the donor liver pool.

Effectiveness of prophylactic antiviral therapy in reducing HBV reactivation for HBsAg-positive recipients following allogeneic hematopoietic stem cell transplantation: a multi-institutional experience from an HBV endemic area.

Hepatitis B virus reactivation (HBVr) is not uncommon in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Hepatitis B surface antigen (HBsAg)-positive patients receiving allo-HSCT have a very high risk of HBVr. However, the validity of prophylactic antiviral treatment in HBsAg-positive allo-HSCT recipients has not been well studied. We aimed to add experience in dealing with HBsAg-positive patients following allo-HSCT. We conducted a cohort study that included 11 years of data of HBsAg-positive allo-HSCT patients in multiple centers. The cumulative incidence of HBVr with antiviral prophylaxis at 60 months following transplantation was 8.9%. Both lamivudine (LAM) and entecavir (ETV) effectively reduced the incidence of HBVr. Patients with absent-mild cGVHD had a lower HBVr rate than that of patients with moderate-severe cGVHD (HR = 0.201, P = 0.020). The incidence of HBsAg seroclearance at 60 months following transplantation was 34.3%. Recipients accepting from anti-HBs-negative donors were associated with a lower HBsAg seroclearance rate than that of those accepting from anti-HBs-positive donors (HR=0.255, P < 0.001). The peripheral blood stem cell (PBSC) donor source had a higher HBsAg seroclearance rates than that of the PBSC plus bone marrow stem cell source (HR = 4.700, P = 0.047). The prophylactic antiviral treatment effectively reduced HBVr in HBsAg-positive recipients receiving allo-HSCT. HBsAg-positive recipients accept anti-HBs-positive PBSC donor sources may facilitate the acquisition of HBsAg seroclearance after transplantation.

Serological and molecular characterization of HBV infection with HBsAg reactive and HBV DNA non-reactive / 中国输血杂志

【Objective】 To investigate the serological and molecular characteristics of HBsAg+ /HBV DNA non-reactive (NR) infections. 【Methods】 Samples tested as HBsAg+ and HBV DNA NR were confirmed by individual NAT repeat testing, viral particle concentration by PEG precipitation combined with in-house nested PCR and real-time quantitative PCR, anti-HBc testing, and HBsAg quantification. HBV sequences were compared with those from donors with chronic and occult infection as controls. 【Results】 A total of 792 195 samples were screened between January 2011 and December 2020, of which 53 (1: 14 947) were confirmed HBsAg+ /HBV DNA NR. HBV DNA was detected further in five (9.4%) samples; three S sequences and four Pre Core/Core sequences were obtained. Unique amino acid substitutions (P130T, P135Q/S, R151Q, G153S and S155F) were found in the Core protein that may affect virus packaging and replication. 【Conclusion】 Extremely low HBV DNA level was detected in plasmas of HBsAg+ /HBV DNA NR donors. Barely detectable HBV DNA might be associated with unusual mutations in the Pre Core/Core protein affecting viral replication. More sensitive HBV DNA and/or HBsAg assays may be considered to further reduce the potential HBV transfusion-transmission residual risk.

The optimal interval for post-vaccination serological test in infants born to mothers with positive hepatitis B surface antigen.

Postvaccination serologic testing (PVST) is utilized to monitor the success or failure of vaccination against hepatitis B virus (HBV) infection in infants of hepatitis B surface antigen (HBsAg) positive mothers. This secondary analysis of 1255 infants of HBsAg-positive mothers at 7-14 months age included in two prospective studies aimed to determine the optimal interval for PVST after three hepatitis B vaccine doses. HBsAg and anti-HBs were quantitatively tested with microparticle enzyme immunoassay. The average PVST interval was 3.8 ± 2.2 months. Overall, 1.7% (21/1255) infants had anti-HBs <10 mIU/mL. The non-response rates were 1.6%, 1.1%, 0.9%, 0.7%, 1.1%, 0.7%, and 5.7% when PVST was performed at an interval of 1, 2, 3, 4, 5, 6, and 7-8 months after the third vaccine dose, respectively. Compared with 1 month of PVST interval, the non-response rate in infants who underwent PVST 7-8 months was significantly higher (χ2 = 4.616, P = .032). Anti-HBs titers were significantly declined in infants with medium responses when PVST was performed with longer intervals (χ2 = 27.592, P < .001), actually declined from interval of 6, and 7-8 months (Z = -3.177, P = .001 and Z = -3.715, P < .001), respectively. These results indicate that PVST may be performed at the age of 7-12 months for infants vaccinated on 0, 1, and 6-month schedule. To identify non-responders as early as possible, we suggest that PVST is performed at 7 months age or 1 month after the final vaccine dose.

Prophylactic antiviral therapy for hepatitis B virus surface antigen-positive patients with diffuse large B-cell lymphoma treated with rituximab-containing chemotherapy.

We conducted a nationwide retrospective analysis of 116 hepatitis B virus (HBV) surface antigen (HBsAg)-positive patients with diffuse large B-cell lymphoma (DLBCL) and 278 HBsAg-negative patients with DLBCL, as a control cohort, who received rituximab-containing regimens as an induction chemotherapy at 30 Japanese medical centers between January 2004 and December 2014. Hepatitis was defined as an absolute serum alanine aminotransferase (ALT) level of ≥100 U/L. HBV reactivation-related hepatitis was defined as hepatitis with an absolute serum HBV DNA level of ≥3.3 log IU/mL or an absolute increase of ≥2 log compared with the baseline value. HBsAg-positive patients were divided into three groups based on anti-HBV prophylactic therapy: no nucleos(t)ide analogue (non-NA, n = 9), lamivudine (LAM, n = 20), and entecavir (ETV, n = 87). The 4-year cumulative incidence (CI) of hepatitis in HBsAg-positive and HBsAg-negative patients was 21.1% and 14.6% (P = .081), respectively. The 4-year CI of HBV reactivation-related hepatitis was higher in HBsAg-positive patients than in HBsAg-negative patients (8.0% vs 0.4%; P < .001). Among HBsAg-positive patients, the 4-year CI of HBV reactivation-related hepatitis was the highest in the non-NA group (33.3%), followed by the LAM (15.0%) and ETV (3.8%) groups (P < .001). Of note, 3 non-NA patients (33%) and 1 LAM patient (5%) (but no ETV patients) died due to HBV hepatitis. Based on Cox multivariate analysis, HBsAg positivity was not associated with poor overall survival. Prophylactic use of ETV would reduce the occurrence of HBV reactivation-related hepatitis and mortality in HBsAg-positive DLBCL patients receiving rituximab-containing chemotherapy.

Kidney Transplantation From Hepatitis B Surface Antigen (HBsAg)-Positive Living Donors to HBsAg-Negative Recipients: Clinical Outcomes at a High-Volume Center in China.

BACKGROUND: Data on kidney transplantation (KTx) from hepatitis B surface antigen (HBsAg)-positive (HBsAg+) donors to HBsAg-negative (HBsAg-) recipients [D(HBsAg+)/R(HBsAg-)] are limited. We aimed to report the outcomes of D(HBsAg+)/R(HBsAg-) KTx in recipients with or without hepatitis B surface antibody (HBsAb). METHODS: Eighty-three D(HBsAg+)/R(HBsAg-) living KTx cases were retrospectively identified. The 384 cases of KTx from hepatitis B core antibody-positive (HBcAb+) living donors to HBcAb-negative (HBcAb-) recipients [D(HBcAb+)/R(HBcAb-)] were used as the control group. The primary endpoint was posttransplant HBsAg status change from negative to postive (-- →+). RESULTS: Before KTx, 24 donors (28.9%) in the D(HBsAg+)/R(HBsAg-) group were hepatitis B virus (HBV) DNA positive, and 20 recipients were HBsAb-. All 83 D(HBsAg+)/R(HBsAg-) recipients received HBV prophylaxis, while no D(HBcAb+)/R(HBcAb-) recipients received prophylaxis. After a median follow-up of 36 months (range, 6-106) and 36 months (range, 4-107) for the D(HBsAg+)/R(HBsAg-) and D(HBcAb+)/R(HBcAb-) groups, respectively, 2 of 83 (2.41%) D(HBsAg+)/R(HBsAg-) recipients and 1 of 384 (0.26%) D(HBcAb+)/R(HBcAb-) became HBsAg+, accompanied by HBV DNA-positive (P = .083). The 3 recipients with HBsAg-→+ were exclusively HBsAb-/HBcAb- before KTx. Recipient deaths were more frequent in the D(HBsAg+)/R(HBsAg-) group (6.02% vs 1.04%, P = .011), while liver and graft function, rejection, infection, and graft loss were not significantly different. In univariate analyses, pretransplant HBsAb-/HBcAb- combination in the D(HBsAg+)/R(HBsAg-) recipients carried a significantly higher risk of HBsAg-→+, HBV DNA-→+, and death. CONCLUSIONS: Living D(HBsAg+)/R(HBsAg-) KTx in HBsAb+ recipients provides excellent graft and patient survivals without HBV transmission. HBV transmission risks should be more balanced with respect to benefits of D(HBsAg+)/R(HBsAg-) KTx in HBsAb-/HBcAb- candidates.

A Novel Strategy for the Prevention of Hepatitis B Virus-Related Hepatitis Following Allogeneic Hematopoietic Stem Cell Transplantation from Hepatitis B Surface Antigen-Positive Donors.

Hematopoietic stem cell transplantation (HSCT) is increasingly being applied globally. Cases in which healthy HSCT donors are chronically infected with hepatitis B virus (HBV) are relatively common in areas where HBV is endemic. Recipients of stem cells from such hepatitis B surface antigen (HBsAg)-positive donors are at risk of viral infection, and thus may develop HBV-related hepatitis. Given the lack of standardized approach to minimizing the risk of such infections from HBsAg+ donors during HSCT, we conducted this study with the aim of developing an efficient strategy to address this challenge. A strategy comprising antiviral treatment for detectable HBV-DNA in HBsAg+ donors, hepatitis B immune globulin (HBIG) administration in HBsAg- recipients with passive immunity, and prophylactic antiviral treatment for HBsAg+ recipients was developed. The strategy was validated using a case-control study of 40 recipients who received stem cells from HBsAg+ donors (group A) and 40 pair-matched controls who received stem cells from HBsAg- donors (group B). The cumulative incidence of HBV-related hepatitis was relatively similar in the 2 groups (group A: 8.5%; 95% confidence interval [CI], -.9% to 17.9%; group B: 7.9%; 95% CI, -.9% to 16.7%; P = .939). In HBsAg- recipients who received passive immunity from HBIG treatment, a significant negative linear correlation was observed between HBsAb titer in vivo and time in the first year after allo-HSCT (R2 = .23; P < .001). This method was cost-effective, with a median cost of all HBV management of USD 332.1 (range, 172.7 to 1985.3), compared with USD 1464.9 (range 409.9 to 1985.3) for conventional strategies (P < .001). The novel strategy presented in here is robust in preventing HBV-related hepatitis after allo-HSCT with stem cells from HBsAg+ donors. This is important for the effective application of allo-HSCT in HBV-endemic areas without precluding the use of HBsAg+ donors.

Optimal timing of antiviral therapy for patients with malignant tumor who presented with hepatitis B reactivation during chemotherapy and/or immunosuppressive therapy.

Background: Hepatitis B virus (HBV) reactivation may occur with chemotherapy and/or immunotherapy. Antiviral prophylaxis is recommended for all patients who are hepatitis B surface antigen (HBsAg)-positive during chemotherapy and/or immunosuppressive therapy. However, the optimal timing of antiviral therapy before chemotherapy and/or immunosuppressive therapy is not fully elucidated. Patients and methods: We retrospectively evaluated 446 HBsAg-positive patients who underwent chemotherapy and/or immunosuppressive therapy. The cumulative rates of HBV reactivation were evaluated using the Kaplan-Meier method and were compared using the log-rank test. The risk factors of HBV reactivation were examined via univariate and multivariate analyses using the Cox proportional hazards model. Results: The cumulative HBV reactivation rates of patients who received antiviral therapy before chemotherapy and/or immunosuppressive therapy were significantly lower than those of patients who received antiviral therapy after chemotherapy and/or immunosuppressive therapy (P = 0.002). The incidence of HBV reactivation was significantly different between patients who received antiviral therapy at least 1 day before chemotherapy and/or immunosuppressive therapy and those who did not (P = 0.006). No significant difference was observed in the HBV reactivation rates between patients who received antiviral therapy at least 2 days (P = 0.310), 3 days (P = 0.494), and 1 week (P = 0.655) before chemotherapy and/or immunosuppressive therapy and those who did not. The multivariate Cox proportional hazards model showed that women had a lower risk of developing HBV reactivation than men (P = 0.025). The use of the prophylactic antiviral agent entecavir, compared with lamivudine and telbivudine, was associated with the decreased risk of developing HBV reactivation (P = 0.002). Conclusion: HBsAg-positive patients who received preemptive antiviral therapy after chemotherapy and/or immunosuppressive therapy had a high risk of developing HBV reactivation. However, it is not necessary for patients to receive antiviral therapy at least 1 week before chemotherapy and/or immunosuppressive therapy.

Rituximab increases the risk of hepatitis B virus reactivation in non-Hodgkin lymphoma patients who are hepatitis B surface antigen-positive or have resolved hepatitis B virus infection in a real-world setting: a retrospective study.

BACKGROUND: Hepatitis B virus (HBV) reactivation with a hepatitis flare is a common complication in lymphoma patients treated with immunotherapy and/or chemotherapy. Anti-HBV prophylaxis is suggested for non-Hodgkin lymphoma (NHL) patients undergoing rituximab therapy, even those with resolved HBV infection. Since anti-HBV prophylaxis for patients with resolved HBV infection is not covered by national health insurance in Taiwan, a proportion of these patients receive no prophylaxis. In addition, late HBV reactivation has emerged as a new issue in recent reports, and no consensus has been reached for the optimal duration of antiviral prophylaxis. Thus, the aim of our study was to investigate the incidence and outcomes of HBV reactivation in NHL patients in a real-world setting and to study the frequency of late HBV reactivation. MATERIALS: Non-Hodgkin lymphoma patients who received rituximab and/or chemotherapy at our institute between January 2011 and December 2015 and who were hepatitis B surface antigen (HBsAg)- or hepatitis B core antibody (HBcAb)-positive were reviewed retrospectively. RESULTS: A total of 388 patients were screened between January 2011 and December 2015. In total, 196 patients were excluded because HBsAg was not assessed, HBcAb was negative or not assessed, or they were not treated with immunosuppressive therapy. Finally, the retrospective study included 62 HBsAg-positive NHL patients and 130 NHL patients with resolved HBV infection (HBsAg-negative and HBcAb-positive). During a median 30.5-month follow-up period, seven patients experienced HBV reactivation, five of whom had a hepatitis flare. The incidence of HBV reactivation did not significantly differ between the HBsAg-positive patients and the resolved HBV infection population without anti-HBV prophylaxis (4.8% vs. 3.1%, P = 0.683). All patients with HBV reactivation were exposed to rituximab. Notably, late HBV reactivation was not uncommon (two of seven patients with HBV reactivation events, 28.6%). Hepatitis B virus reactivation did not influence the patients' overall survival. An age ≥65 years and an advanced disease stage were independent risk factors for poorer overall survival. CONCLUSION: The incidence of HBV reactivation was similar between the HBsAg-positive patients with antiviral prophylaxis and the resolved HBV infection population without anti-HBV prophylaxis. All HBV reactivation events occurred in NHL patients exposed to rituximab. Late reactivation was not uncommon. The duration of regular liver function monitoring for more than 1 year after immunosuppressive therapy or after withdrawal of prophylactic antiviral therapy should be prolonged. Determining the exact optimal duration of anti-HBV prophylaxis is warranted in a future prospective study for NHL patients treated with rituximab-containing therapy.

A prospective cohort study on the risk of HBV infection in preschool children without immune response to hepatitis B vaccine / 中华疾病控制杂志

@# Objective To evaluate the risk of hepatitis B virus(HBV) infection among preschool children who were the non-responders to hepatitis B vaccine in future. Methods A prospective cohort study was conducted. Children aged 2 to 5 years were selected from 64 kindergartens.These children were inoculated three doses of hepatitis b vaccine at 0, 1 and 6 months after birth. Hepatitis B surface antigen (HBsAg)and Hepatitis B surface antibody (anti-HBs)were detected during the period from March to May 2015. The children who were HBsAg negative were enrolled in the study. The subjects were divided into exposure group (anti-HBs negative) and control group (anti-HBs positive) . The follow-up began on June 1, 2015 and ended on June 1, 2016. Serum HBsAg of children in the cohort was then collected and detected from June 1 to 30, 2016. At the end of the study, the HBsAg positive rates between two groups were compared. Results 83 children who received hepatitis B vaccine again during the follow-up period were excluded from 1 907 non-responders. The actual number in non-responders group was 1 824. 151 children were lost at the end of the study. The actual number of follow-up was 1 673 and 5 children were found to be positive for HBsAg and the infection rate was 0.30% (5/1673). In the respondent goup, 2 054 were enrolled and followed. Finally, 140 children were lost and none of the remaining 1 914 people were HBsAg positive at the end of the study. HBsAg positive rate was higher in the non-responder group than in the responder group (P=0.023). Conclusion There is a risk of HBV infection in the children who are non-responders to hepatitis B vaccine in future.

[Relationship between the HBsAg-positive infection status of mothers and the non/low-response to hepatitis B vaccine of their infants].

Objective: To explore the relationship between the status of HBsAg-positive infection of mothers and the non/low-response to hepatitis B vaccine of their infants. Methods: A total of 225 pairs of mothers and their infants were recruited in our cohort from June 2011 to July 2013. Infants were given three doses of hepatitis B vaccine at hour 24, first month and month 6(t)h respectively and were followed up for one year after birth. HBV serological markers and HBV DNA in the peripheral blood of both mothers and infants were detected by Electro-chemiluminescence immunoassay and fluorescence quantitative Polymerase Chain Reaction. Results: Six HBV infection models were detected in HBsAg-positive mothers, and "HBsAg (+), HBeAg (+), anti-HBc (+)" (model one) and "HBsAg (+), anti-HBe (+), anti-HBc (+)" (model two) accounted for 92.5%(208/225) of all the models. Rate of non/low-response to hepatitis B vaccine in infants born to mothers in model one was lower than those in model two, the differences are statistically significant (χ(2)=4.80, P=0.029). The rate of non/low-response to hepatitis B vaccine in infants showed a downward trend with the rising of HBeAg level in their mothers (χ(2)=4.86, P=0.028). Results from the unconditional logistic regression analysis showed that the HBeAg of the HBsAg-positive mothers was significantly correlated with the low risk of non/low-response to hepatitis B vaccine in infants (OR=0.598, 95%CI: 0.378-0.947). The positive rate of serum HBV DNA in HBsAg-positive mothers was 54.2%, while the rate of non/low-response to hepatitis B vaccine in infants born to HBV DNA positive mothers was similar to those infants born to HBV DNA negative mothers (χ(2)=0.22, P=0.640). Conclusions: "HBsAg (+), HBeAg (+), anti-HBc (+)" and "HBsAg (+), anti-HBe(+), anti-HBc (+)" were the common models seen in HBsAg-positive mothers, and the rate of non/low-response to hepatitis B vaccine was different between the two models. HBeAg of HBsAg-positive mothers might have positive effects on the immune response to hepatitis B vaccine in infants but the mechanisms remained not clear. HBV DNA of the HBsAg-positive mothers did not seem to be correlated with the immune response to hepatitis B vaccine in infants.

Discontinuation of antiviral prophylaxis increased the risk of hepatitis B virus reactivation in glomerulonephritis patients under immunotherapy: a real-life observation.

PURPOSE: Antiviral prophylaxis is proved to be effective in reducing the risk of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-positive patients under immunotherapy. But outcomes referring to discontinuation of antiviral prophylaxis in these patients are lacking. METHODS: We performed a retrospective study of 105 HBsAg-positive patients under immunotherapy for glomerulonephritis and evaluated the incidence and risk factors for HBV reactivation. RESULTS: Among 105 patients, 55.24% completed antiviral prophylaxis, while 20.00% discontinued and 24.76% rejected antiviral prophylaxis. HBV reactivation was significantly different among completion, discontinuation, and rejection of antiviral prophylaxis: 5.17% versus 38.10% versus 15.38% in the incidence of HBV reactivation (P = 0.001), 3.45% versus 23.81% versus 11.54% in HBV DNA ≥ 5 Log copies/ml (P = 0.023), and 0 versus 14.29% versus 3.85% in hepatitis B e antigen seroconversion from negative to positive (P = 0.014). Survival curve showed the median occurrence time of HBV reactivation in discontinuation group was 32 months (95% CI 24-39 months), earlier than 69 months (95% CI 65-72 months) of completion group and 43 months (95% CI 37-49 months) of rejection group (χ2 = 13.780, P = 0.001). Univariate and multivariate analysis identified two independent risk factors for HBV reactivation: baseline HBV DNA detectable (OR 5.009, 95% CI 1.717-16.335, P = 0.012) and discontinuation of antiviral prophylaxis (OR 5.213, 95% CI 1.688-18.105, P = 0.011). CONCLUSIONS: Discontinuation of antiviral prophylaxis increased the risk of HBV reactivation in HBsAg-positive patients under immunotherapy for glomerulonephritis.

Analysis of clinical features and pathology of serum HBsAg positive glomerulonephritis.

To analyze the relationship between the factors related to the occurrence of HBV-GN and serum HBsAg-positive glomerulonephritis. A total of 56 patients were enrolled in the present study. All enrolled cases were divided into two groups according to whether HBsAg and/or HBcAg was present in renal kidney tissue: patients with Hepatitis B virus-associated nephritis (HBV-GN group, 30 cases) and patients with hepatitis B virus-combined nephritis (HBV-CG group, 26 cases). We sought to analyze the differences in clinical features and pathological characteristics in both groups. The rate of HBeAg positivity in the HBV-GN group was considerably increased in the HBV-CG group (P < 0.05), and the number of patients with HBsAg+HBeAg+HBcAb+ in the HBV-GN group was considerably increased in the HBV-CG group (21 cases vs 10 cases) (P < 0.05). Moreover, the number of MCD patients diagnosed by renal biopsy in the HBV-GN group was reduced compared with the HBV-CG group (1 case vs 7 cases) (P < 0.05). HBV infection and high-virus proliferation status were closely related with HBV-GN.

Relationship between the HBsAg-positive infection status of mothers and the non/low-response to hepatitis B vaccine of their infants / 中华流行病学杂志

Objective To explore the relationship between the status of HBsAg-positive infection of mothers and the non/low-response to hepatitis B vaccine of their infants.Methods A total of 225 pairs of mothers and their infants were recruited in our cohort from June 2011 to July 2013.Infants were given three doses of hepatitis B vaccine at hour 24,first month and month 6th respectively and were followed up for one year after birth.HBV serological markers and HBV DNA in the peripheral blood of both mothers and infants were detected by Electro-chemiluminescence immunoassay and fluorescence quantitative Polymerase Chain Reaction.Results Six HBV infection models were detected in HBsAg-positive mothers,and "HBsAg (+),HBeAg (+),anti-HBc (+)" (model one) and "HBsAg (+),anti-HBe (+),anti-HBc (+)" (model two) accounted for 92.5％ (208/225) of all the models.Rate of non/low-response to hepatitis B vaccine in infants born to mothers in model one was lower than those in model two,the differences are statistically significant (x2=4.80,P=0.029).The rate of non/low-response to hepatitis B vaccine in infants showed a downward trend with the rising of HBeAg level in their mothers (x2=4.86,P=0.028).Results from the unconditional logistic regression analysis showed that the HBeAg of the HBsAg-positive mothers was significantly correlated with the low risk of non/low-response to hepatitis B vaccine in infants (OR=0.598,95％CI:0.378-0.947).The positive rate of serum HBV DNA in HBsAg-positive mothers was 54.2％,while the rate of non/low-response to hepatitis B vaccine in infants born to HBV DNA positive mothers was similar to those infants born to HBV DNA negative mothers (X2=0.22,P=0.640).Conclusions "HBsAg (+),HBeAg (+),anti-HBc (+)" and "HBsAg (+),anti-HBe(+),anti-HBc (+)" were the common models seen in HBsAg-positive mothers,and the rate of non/low-response to hepatitis B vaccine was different between the two models.HBeAg of HBsAg-positive mothers might have positive effects on the immune response to hepatitis B vaccine in infants but the mechanisms remained not clear.HBV DNA of the HBsAg-positive mothers did not seem to be correlated with the immune response to hepatitis B vaccine in infants.

Relationship between the HBsAg-positive infection status of mothers and the non/low-response to hepatitis B vaccine of their infants / 中华流行病学杂志

Objective To explore the relationship between the status of HBsAg-positive infection of mothers and the non/low-response to hepatitis B vaccine of their infants.Methods A total of 225 pairs of mothers and their infants were recruited in our cohort from June 2011 to July 2013.Infants were given three doses of hepatitis B vaccine at hour 24,first month and month 6th respectively and were followed up for one year after birth.HBV serological markers and HBV DNA in the peripheral blood of both mothers and infants were detected by Electro-chemiluminescence immunoassay and fluorescence quantitative Polymerase Chain Reaction.Results Six HBV infection models were detected in HBsAg-positive mothers,and "HBsAg (+),HBeAg (+),anti-HBc (+)" (model one) and "HBsAg (+),anti-HBe (+),anti-HBc (+)" (model two) accounted for 92.5％ (208/225) of all the models.Rate of non/low-response to hepatitis B vaccine in infants born to mothers in model one was lower than those in model two,the differences are statistically significant (x2=4.80,P=0.029).The rate of non/low-response to hepatitis B vaccine in infants showed a downward trend with the rising of HBeAg level in their mothers (x2=4.86,P=0.028).Results from the unconditional logistic regression analysis showed that the HBeAg of the HBsAg-positive mothers was significantly correlated with the low risk of non/low-response to hepatitis B vaccine in infants (OR=0.598,95％CI:0.378-0.947).The positive rate of serum HBV DNA in HBsAg-positive mothers was 54.2％,while the rate of non/low-response to hepatitis B vaccine in infants born to HBV DNA positive mothers was similar to those infants born to HBV DNA negative mothers (X2=0.22,P=0.640).Conclusions "HBsAg (+),HBeAg (+),anti-HBc (+)" and "HBsAg (+),anti-HBe(+),anti-HBc (+)" were the common models seen in HBsAg-positive mothers,and the rate of non/low-response to hepatitis B vaccine was different between the two models.HBeAg of HBsAg-positive mothers might have positive effects on the immune response to hepatitis B vaccine in infants but the mechanisms remained not clear.HBV DNA of the HBsAg-positive mothers did not seem to be correlated with the immune response to hepatitis B vaccine in infants.

Influence of universal HBV vaccination on chronic HBV infection in Italy: Results of a cross-sectional multicenter study.

BACKGROUND AND AIM: The universal hepatitis B vaccination for infants and 12-year-old adolescents (the latter limited to the first 12 years of application) was launched in Italy in 1991. Twenty-three years later we evaluated the impact of the vaccination campaign on the burden of HBsAg-positive chronic liver diseases (CLD). MATERIAL AND METHODS: A total of 513 HBsAg-positive chronic carriers referring to 16 Italian liver units were investigated and compared with HBsAg carriers enrolled in previous surveys. RESULTS: The proportion of inactive carriers decreased from 20.0% in 2001 to 3.3% in 2014, while that of cirrhotic patients increased from 22.6% to 33.2%. Regarding the age class 0-33 (fully covered by HBV vaccination in 2014), the rate of inactive carriers decreased from the 21.7% in 2001 to 5.9% in 2014, that of chronic hepatitis from 17.5% to 5.2% and that of cirrhosis cases from 26.4% to 4.1%. Instead, in the over-60 age group the rate of inactive carriers increased from 22.8% to 41.2% and that of chronic hepatitis from 16.8% to 46%; the rate of patients with cirrhosis ranged from 5% to 8% in different studies. CONCLUSION: Twenty-three years after the introduction universal HBV vaccination in Italy, the clinical presentation of CLD had shown a shift toward older ages and more severe diseases.