Hepatitis B Immunoglobulin Research Articles

Aile Hekimlerinin Maternal Kronik Hepatit B Enfeksiyonu Yönetimi Hakkındaki Farkındalık Durumu

Giriş ve Amaç: Hepatit B virüs (HBV) enfeksiyonu tüm dünyada giderek azalma eğiliminde olan halk sağlığı açısından önemli bir hastalıktır. HBsAg pozitif saptanan gebede hastalığın şiddeti ve tedavi gerekip gerekmediği yakın takip edilmelidir. Bu çalışmada gebelik ve bebek takiplerinin yakından izleminin yapıldığı birinci basamak aile hekimlerinde maternal kronik hepatit B yönetimi hakkındaki farkındalıklarını belirlemeyi amaçladık.
 Yöntem: Çalışmaya birinci basamak sağlık hizmetlerinde görev yapmakta olan aile hekimleri dahil edildi. Katılımcılara maternal kronik hepatit B enfeksiyonu yönetimi ile ilgili ve elektronik ortamda doldurabilecekleri anket soruları oluşturuldu. 
 Bulgular: Çalışmamıza 125 (%57.1)’i kadın ve 94 (%42.9)’ü erkek olmak üzere toplam 219 hekim katıldı. Hekimlerin 43 (%19.6)’ü aile hekimi uzmanı, 97 (%44.3)’si aile hekimliği asistanı ve 79 (%36.1)’i pratisyen hekim olarak çalışmaktaydı. Katılımcıların yaş ortalaması 31±7.36 yıl, çalışma yılı ortalaması 5±7.6 yıl idi. Hekimlere hepatit B enfeksiyonu hakkında yeterli bilgiye sahip olup olmadıklarını sorduk. 137 (%62.6) hekim yeterli bilgiye sahip olduğunu belirtti. Hekimlerin 126 (%30.5)’sı hepatit B virüsünün anneden bebeğe intrauterin dönemde geçtiğini, 195 (%47.2)’i doğum esnasında ve 92 (%22.3)’si postnatal dönemde geçtiğini ifade etti. Katılımcıların 187 (%85.4)’sinin emzirmede sakınca olmadığını belirtti. 184 (%84) hekim gebelik döneminde annelere hepatit B enfeksiyonu taraması yapıldığını, 143 (%65.3) hekim HBsAg ve AntiHBs negatif olan gebeye gebelik döneminde hepatit B aşısı yapılabileceğini belirtti. Katılımcıların 156 (%36.4)’sı HBsAg pozitif tespit edilen gebeyi enfeksiyon hastalıkları veya gastroenteroloji uzmanına yönlendirdiğini, hepatit B’li anne bebeğine hepatit B aşısı ve hepatit B immünglobulin yapılmalıdır diyen hekimlerin sayısı sırasıyla 178 (%40.6) ve 197 (%45) idi. Hepatit B’li anneden doğan bebeğin takibinde 163 (%38.5) hekim “HBsAg pozitif saptanan bebeği pediatrik enfeksiyon kliniğine yönlendiririm”, 76 (%18) hekim “hepatit B aşı uygulamasından sonra AntiHBs bakarım”, 72 (%17) hekim “hepatit B aşı uygulamasından sonra HBsAg bakarım” ve 112 kişi “AntiHBs

Long-term outcome after prevention of de novo hepatitis B in recipients of core antibody-positive livers with hepatitis B immunoglobulin only

Background: Anti-HBc positive donors represent an important source of organs in hepatitis B virus (HBV) endemic areas despite the risk of occult HBV infection. We analyzed long-term outcome of prevention for de novo HBV with hepatitis B immunoglobulin (HBIG) only after liver transplantation (LT) using core-positive grafts. Methods: We retrospectively reviewed the prospective collected data of 1,479 recipients between 1988 and 2018 at Seoul Nation al University Hospital. 1,458 were eligible and enrolled. If either donor or recipient had core antibody, HBIG 4000 IU was adminis trated 4 times until postoperative day 3. Results: Of 1,458 LTs, 478 (32.8%) used anti-HBc positive grafts. Three hundred twenty-six (68.2%) was allocated to hepatitis B surface antigen (HBsAg)-positive recipients, with 152 (31.8%) to HBs-negative recipients. 21 (13.8%) of de novo HBV infection occurred in 152 core-positive grafts. One (25%), 11 (22.4%), 0, 9 (9.2%) was diagnosed of de novo HBV infection in 4 of hepatitis B surface antigen (HBcAb) and HBsAb negative, 49 of HBcAb-negative and HBsAb-positive, 1 of HBcAb-positive and HBsAb-neg ative, 98 of HBcAb and HBsAb positive recipients respectively. Anti-HBc negative recipients were more likely to develop de novo HBV infection compared with anti-HBc positive recipients (22.6% vs. 9.1%, P=0.021). Incidence of de novo HBV infection did not differ by recipient HBsAb status (P=0.530). The median follow-up time was 69 months (range, 29-165 months). The median time to detection of HBsAg seropositivity was 18 months (range, 8-55 months). Two had no treatment, twelve were treated with nu cleoside analogs (NA) monotherapy, and seven were treated with NA plus HBIG. The median treatment duration was 41 months. Seven acquired seroconversion. There were 42 (8.8%) of graft losses in study period. The 1-, 5-, 10-year patient survival with an ti-HBc positive liver were 97.5%, 93.2%, and 90.5%. No patient died of de novo HBV infection. Conclusions: De novo HBV did not affect patient survival. However, HBIG only prophylaxis was not enough to prevent de novo HBV development in the era of NA.

Progress towards elimination of mother-to-child transmission of hepatitisB virus infection in China: a modelling analysis.

To determine the projected burden of hepatitisB virus (HBV) in China, the intervention strategies that can eliminate mother-to-child transmission (MTCT) by 2030 or earlier and the measurable parameters that can be used to monitor progress towards this target. We developed a dynamic, sex- and age-stratified model of the HBV epidemic in China, calibrated using hepatitis B surface antigen (HBsAg) and e antigen (HBeAg) prevalence data from sequential national serosurveys (1979-2014) and the numbers of HBV-related cancer deaths (2012). We determined whether China can achieve elimination of MTCT of HBV by 2030 under current prevention interventions. We modelled various intervention scenarios to represent different coverage levels of birth-dose HBV vaccination, hepatitisB immunoglobulin to newborns of HBsAg-positive mothers and antiviral therapy (tenofovir) to HBeAg-positive pregnant women. We project that, if current levels of prevention interventions are maintained, China will achieve the elimination target by 2029. By modelling various intervention scenarios, we found that this can be brought forward to 2025 by increasing coverage of birth-dose vaccination, or to 2024 by the administration of tenofovir to HBeAg-positive pregnant women. We found that achievement of the target by 2025 would be predicted by a measurement of less than 2% MTCT in 2020. Our results highlight how high-quality national data can be combined with modelling in monitoring the elimination of MTCT of HBV. By demonstrating the impact of increased interventions on target achievement dates, we anticipate that other high-burden countries will be motivated to strengthen HBV prevention policies.

HEPATITIS B IMMUNOGLOBULIN PROPHYLAXIS FOR PREVENTION OF DE NOVO HEPATITIS B INFECTION FROM HEPATITIS B CORE ANTIBODY-POSITIVE DONORS

Introduction: Recently, hepatitis B core antibody (anti-HBc) positive liver grafts are used as extended criteria donor organs. However, prophylaxis methods to prevent de novo hepatitis B virus (HBV) infection after liver transplantation (LT) are still controversial. Thus, the purpose of our study is to evaluate the risk and outcomes of receiving anti-HBc positive grafts with prophylactic HBIG monotherapy. Method: All adult patients who underwent LT at Samsung Medical Center in Seoul, Korea, between January 2001 and December 2018 were gathered from a prospectively maintained database and reviewed retrospectively. HBV patients received the combination treatments with antiviral prophylaxis and hepatitis B immunoglobulin (HBIG). Prophylactic HBIG monotherapy was given for patients without HBV receiving grafts from anti-HBc positive donors. Results: A total of 1355 patients underwent LT during this period. Among them, 457 (33.7%) were anti-HBc positive and 898 (66.3%) were anti-HBc negative donors, who underwent follow-up for a median time of 5.7 years. Perioperative outcomes (mortality in 30 days, complications and postoperative ICU stay period) were similar between the two groups. Also, there were no significant difference in the 1-, 5-, 10- and 15-year patient survival rates between the anti-HBc positive (87.5%, 73.5%, 67.7% and 61.2%) and the anti-HBc negative groups (88.5%, 77.7%, 70.7% and 69.6%, p = 0.080). All of the 117 recipients who were HBsAg negative and received anti-HBc positive grafts were given prophylactic HBIG monotherapy. Only one patient (0.9%, 1/117) developed de novo HBV during follow-up. There were 972 HBsAg-positive patients and 348 (35.8%) received anti-HBc positive grafts. The risk of HBV recurrence was similar between 2 groups (p = 0.308). The donor anti-HBc status did not have a significant influence on the long-term survival or the risk of de novo or recurrent HBV infection after LT.Conclusion: De novo HBV was very rare especially with HBIG prophylaxis in non-HBV patients received anti-HBc positive liver graft. There was no significant influence of anti-HBc positive grafts on the perioperative and long-term outcomes after LT.

A recombinant human immunoglobulin with coherent avidity to hepatitis B virus surface antigens of various viral genotypes and clinical mutants.

The hepatitis B virus (HBV) envelope is composed of a lipid bilayer and three glycoproteins, referred to as the large (L), middle (M), and small (S) hepatitis B virus surface antigens (HBsAg). S protein constitutes the major portion of the viral envelope and an even greater proportion of subviral particles (SVP) that circulate in the blood. Recombinant S proteins are currently used as a preventive vaccine, while plasma fractions isolated from vaccinated people, referred to as hepatitis B immune globulin (HBIG), are used for short-term prophylaxis. Here, we characterized a recombinant human IgG1 type anti-S antibody named Lenvervimab regarding its binding property to a variety of cloned S antigens. Immunochemical data showed an overall consistent avidity of the antibody to S antigens of most viral genotypes distributed worldwide. Further, antibody binding was not affected by the mutations in the antigenic 'a' determinant found in many clinical variants, including the immune escape mutant G145R. In addition, mutations in the S gene sequence that confer drug resistance to the viral polymerase did not interfere with the antibody binding. These results support for a preventive use of the antibody against HBV infection.

English

There was an accidental death of BALB/c mice in the course of the experiment about hepatitis B immunization. The reasons of the mice breeding failure were analyzed in order to provide some experience for future animal preparation about hepatitis B immunization. Items of all mice including sex, age, dose of hepatitis B vaccine (HepBVac), dose of hepatitis B immunoglobulin (HBIG), immunization route, vaccination schedule and the acclimatization period were recorded before the first immunization. Among 334 mice included, the survival rates in different groups of initial ages were 45.9% in 3-week-old, 49.3% in 4-week-old, 51.9% in 5-week-old, 84.8% in 7-week-old and 96.6% in 8-week-old; the survival rate in seven days acclimatization group was 96.6% and 53.3% in one day acclimatization group. Multivariate logistic regression analysis indicated that smaller ages (3 weeks, 4 weeks) and acclimatization for only one day were the independent risk factors affecting the survival of mice. Multivariate logistic regression analysis showed that injection with HBIG, lower dose of HepBVac and hypodermic injection were independent risk factors for low-and non-response to HepB Vac. It is suggested that the mice should be more than five-week-old and must have acclimated to the environment for one week before the experiment begins. The initial ages of the mice have no impact on their immune efficacy. Key words: BALB/c mice, age, acclimatization, hepatitis B immunization.  

Increased Protection of Earlier Use of Immunoprophylaxis in Preventing Perinatal Transmission of Hepatitis B Virus.

Passive-active immunoprophylaxis against mother-to-child transmission (MTCT) of hepatitis B virus (HBV) recommends administering hepatitis B immunoglobulin (HBIG) and birth-dose hepatitis B vaccine in infants within 12 or 24 hours after birth. With this protocol, MTCT of HBV still occurs in 5-10% infants of HBV-infected mothers with positive hepatitis B e antigen (HBeAg). The present study aimed to investigate whether earlier administration of HBIG and hepatitis B vaccine after birth can further increase protection efficacy. We conducted a prospective, multi-center observational study in infants born to mothers with HBV infection, in whom neonatal HBIG and birth dose hepatitis B vaccine were administered within one hour after birth. The infants were followed up for HBV markers at 7-14 months of age. A total of 1140 pregnant women with HBV were enrolled, and 982 infants (9 twins) of 973 mothers were followed up at 9.6 ± 1.9 months of age. HBIG and birth-dose vaccine were administered in newborn infants within a median of 0.17 (0.02-1.0) hours after birth. The overall rate of MTCT was 0.9% (9/982), with none (0%) of the 607 infants of HBeAg-negative mothers and 9 (2.4%) of 375 infants of HBeAg-positive mothers acquiring HBV. All 9 HBV-infected infants were born to mothers with HBV DNA >2.75 × 106 IU/mL. Maternal HBV DNA levels >2 × 106 IU/mL were an independent risk factor (odds ratio, 10.627; 95% confidence interval, 2.135-∞) for immunoprophylaxis failure. Earlier use (within 1 hour after birth) of HBIG and hepatitis B vaccine can provide better protection efficacy against MTCT of HBV.

Prevention of HBV Recurrence after Liver Transplant: A Review.

Globally, hepatitis B virus (HBV) infection is recognized as a major risk factor for the development of hepatocellular carcinoma, and HBV-induced liver failure is one of the leading indications for liver transplantation. Until about two decades ago, liver transplantation in patients with chronic HBV infection was a relative contraindication, due to high risk of viral replication with the use of immunosuppressants which could result in graft infection. In the 1990s, hepatitis B immunoglobulin (HBIg) use significantly reduced the risk of graft infection, improving outcomes of liver transplant in patients with chronic HBV infection. However, very high costs, especially with the need for long-term use, became a major concern. With the advent of nucleos(t)ide analogs (NAs), there was less need for high-dose, long-term HBIg use to prevent HBV recurrence. Lamivudine was initially used but resistance soon became a major issue. This was followed by more potent NAs, such as entecavir and tenofovir, emerging as the more preferred agents. Additionally, the use of these antiviral agents (HBIg and/or NAs) have made it possible to use the grafts from donors with positivity for hepatitis B core antibody, allowing for expansion of the donor pool. Nevertheless, there is no consensus on management protocols, which vary significantly amongst centers. In this review, we appraise studies on management strategies used and the role of active vaccination in the prevention of HBV recurrence in post-liver transplant patients.

Hepatitis B Immunoglobulin discontinuation in long-term liver transplant patients.

Hepatitis B immunoglobulin (HBIG)-as a monotherapy or combined with nucleos(t)ide analogs (NUCs)-has effectively lowered Hepatitis B virus (HBV) reinfection after liver transplantation. However, it is associated with high costs and viral resistance. HBIG-free prophylaxis with novel NUCs (tenofovir, entecavir) composes a viable alternative. We evaluated reinfection rate, histological changes, and outcome associated with HBIG discontinuation. A retrospective analysis was performed of patients undergoing liver transplantation due to HBV-induced liver disease at our center since 1988. A controlled HBIG discontinuation was conducted between 2015 and 2017 in 65 patients. Recurrent infection was determined by HbsAg values. Fibrosis and inflammation were evaluated by routine biopsy. The survival of patients after HBIG discontinuation was compared to a control population on HBIG for prophylaxis. From 1988 to 2013, 352 patients underwent liver transplantation due to HBV-induced liver disease. 169 patients could be included for analysis. 104 (51.5%) patients continued a prophylaxis containing HBIG. HBIG was discontinued in 65 (38.5%) patients in a controlled manner, maintaining an oral NUC. None of those patients showed HBV reinfection or graft dysfunction. No significant changes of inflammation grades (P=.067) or fibrosis stages (P=.051) were detected. The survival of patients after HBIG discontinuation was comparable to the control (P=.95). HBIG withdrawal under continuation of oral NUC therapy is safe and not related to graft dysfunction, based on blood tests and histology. HBIG-free prophylaxis is not associated with a worse outcome and displays a financial relief as well as a logistic simplification during long-term follow-up.

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.

Hepatitis B Prophylaxis after Liver Transplantation in Korea: Analysis of the KOTRY Database.

BackgroundProphylaxis for hepatitis B virus (HBV) recurrence is essential after liver transplantation (LT) in HBV-associated recipients. We conducted real-world analysis of HBV prophylaxis after LT in the Korean population.MethodsKorean Organ Transplantation Registry (KOTRY) database and additionally collected data (n = 326) were analyzed with special reference to types of HBV prophylaxis.ResultsThe study cohort comprised 267 cases of living-donor LT and 59 cases of deceased-donor LT. Hepatocellular carcinoma (HCC) was diagnosed in 232 (71.2%) of these subjects. Antiviral agents were used in 255 patients (78.2%) prior to LT. HBV DNA was undetectable in 69 cases (21.2%) and detectable over wide concentrations in the other 257 patients (78.8%) prior to LT. Polymerase chain reaction analysis of the store blood samples detected HBV DNA in all patients, with 159 patients (48.9%) showing concentrations > 100 IU/mL. Post-transplant HBV regimens during the first year included combination therapy in 196 (60.1%), hepatitis B immunoglobulin (HBIG) monotherapy in 121 (37.1%), and antiviral monotherapy in 9 (2.8%). In the second post-transplant year, these regimens had changed to combination therapy in 187 (57.4%), HBIG monotherapy in 112 (34.4%), and antiviral monotherapy in 27 (8.3%). Trough antibody to hepatitis B surface antigen titers > 500 IU/mL and >1,000 IU/mL were observed in 61.7% and 25.2%, respectively. The mean simulative half-life of HBIG was 21.6 ± 4.3 days with a median 17.7 days. Up to 2-year follow-up period, HCC recurrence and HBV recurrence developed in 18 (5.5%) and 6 (1.8%), respectively. HCC recurrence developed in 3 of 6 patients with HBV recurrence.ConclusionCombination therapy is the mainstay of HBV prophylaxis protocols in a majority of Korean LT centers, but HBIG was often administered excessively. Individualized optimization of HBIG treatments using SHL is necessary to adjust the HBIG infusion interval.

Retrospective Review of Documentation Practices of Hepatitis B Immunoglobulin, Birth Dose, and Vaccination at the Hospital of Birth, in Thai Nationals and Migrants in Northern Thailand

BackgroundVaccination remains the mainstay of prevention of hepatitis B virus (HBV) including birth dose and hepatitis B immunoglobulins (HBIGs). National estimates of vaccination coverage exclude migrants. The objective of this study is to investigate documentation practices of HBV-related infant vaccinations in Northern Thailand including migrants.MethodsThis is a retrospective review of hospital records of women who birthed infants in 2015 at Maharaj Nakorn Hospital, Chiang Mai (CM) or on the Thailand-Myanmar border, Tak.ResultsOf 2522 women, 987 were from CM (861 Thai nationals, 126 migrants) and 1535 were from Tak (651 Thai residence and 884 Myanmar residence). In CM, documentation for the birth dose vaccine (999 of 999, 100%) and HBIG was complete. In Tak, documentation was 1441 of 1549 (93%) for birth dose and 26 of 34 (76.5%) for HBIG, with missed opportunities including home delivery, delay in obtaining hepatitis B e-antigen status, and limitations of the records. Expanded Program of Immunization (EPI) documentation of 3 follow-up vaccinations dwindled with subsequent doses and distance, and complete documentation of 3 HBV EPI vaccines at the hospital of birth was low, 41.5% (1056 of 2547), but equitable for Thai or migrant status.ConclusionsThis review provides strong support for excellent documentation of HBIG and birth dose vaccination in urban and rural settings, and in migrants, consistent with Thailand’s vaccination policy and practice. Documentation of the 3 HBV EPI at the hospital of birth decreases with sequential doses, especially in families further away. Innovative data linkage is required to prove coverage and identify gaps.

Cost-effectiveness of augmenting universal hepatitis B vaccination with immunoglobulin treatment: a case study in Zhejiang Province, East China

ABSTRACT Objective To evaluate the cost-effectiveness of the current strategy combining universal vaccination with hepatitis B immunoglobulin (HBIG) treatment for infants of hepatitis B surface antigen (HBsAg) positive mothers compared with universal vaccination with hepatitis B vaccine only. Methods A decision tree model with a Markov process was constructed and used to simulate the lifetime of the birth cohort in Zhejiang Province during 2016. The current strategy was compared against universal vaccination with respect to costs and health effects. Costs were assessed from the health care system perspective. Health effects were measured by the number of hepatitis B virus (HBV) related diseases and deaths avoided and quality-adjusted life-years (QALYs) gained. The incremental cost‑effectiveness ratio (ICER) is calculated and compared to standard willingness-to-pay thresholds. A one-way sensitivity analysis and a probabilistic sensitivity analysis (PSA) were performed to assess parameter uncertainties. Results Over the cohort’s lifetime, 182 acute symptomatic infections, 2215 chronic infections, 872 cases of cirrhosis, 595 cases of hepatocellular carcinoma (HCC) and 1,350 HBV-related deaths among the cohort of 624,000 infants would be further avoided by the current strategy compared to universal vaccination. Universal vaccination was dominated by the current strategy that produced not only higher total QALYs, but also had lower costs. The results remained robust over a wide range of assumptions. Conclusions The current strategy was cost saving compared to universal vaccination, and continuing the current strategy is recommended to further decrease the burden of hepatitis B.

Mechanism and Antiviral Therapy in Preventing Mother-to-Child Transmission During Pregnancy with Hepatitis B Virus Infection

Context: Mother-to-child transmission (MTCT) is one of the main transmission routes of chronic hepatitis B virus (HBV) infection. The successful rate of preventing MTCT has increased to over 90% after the administration of passive-active immunoprophylaxis (vaccine and hepatitis B immunoglobulin (HBIG)) on infants born to hepatitis B surface antigen (HBsAg)-positive mothers. However, 5%-10% of the infants had chronic HBV infection who were born to mothers with high HBV DNA levels. Therefore, the current domestic and international guidelines recommended that antiviral therapy in late pregnancy was to further decrease the MTCT rate. This study aimed at reviewing the mechanisms of MTCT and controversial issues in antiviral therapy for pregnant women with high viral load in order to provide clinicians with some strategies for preventing MTCT of HBV. Evidence Acquisition: Relevant English published papers were searched using online databases, including PubMed and EMBASE from January 2000 to January 2019. We summarized the findings of 61 relevant studies in this review. Results: The mechanism of MTCT is still unclear and further studies are needed. Antiviral therapy for pregnant women with high viral load can reduce the rate of MTCT and provide the appropriate safety for mothers and infants. Conclusions: The mechanisms underlying MTCT of HBV is still unknown and more investigations are required. The efficacy and safety of taking tenofovir disoproxil fumarate (TDF) orally in pregnant women with high viral load in the second or third trimester of pregnancy to block MTCT of HBV have been proved. The withdrawal of antiviral therapy during pregnancy due to MTCT should not exceed 3 months after delivery at the latest. Most pregnant women tend to suffer from increased alanine aminotransferase (ALT) after discontinuing antiviral drugs during pregnancy. Accordingly, close ALT levels monitoring after drug discontinuation is essential.

Efficacy of Lenvervimab, a Recombinant Human Immunoglobulin, in Treatment of Chronic Hepatitis B Virus Infection

The mechanism of action of hepatitis B immunoglobulin (HBIG) for chronic hepatitis B (CHB) treatment is not fully understood. A clinical trial in Japan suggested that HBIG therapy might benefit patients with CHB.1 Lenvervimab, a recombinant monoclonal HBIG developed by GC Pharma (Yongin, South Korea), has been screened from an anti-HBs-enriched phage-display library cloned from hepatitis B vaccine-boosted human blood cells and was produced in Chinese hamster ovary cells.2-4.

Recent Progress on Neutralizing Antibodies against Hepatitis B Virus and its Implications.

Hepatitis B virus (HBV) infection remains a global health problem. As "cure" for chronic hepatitis B is of current priority, hepatitis B immunoglobulin (HBIG) has been utilized for several decades to provide post-exposure prophylaxis. In recent years, a number of monoclonal antibodies (mAbs) targeting HBV have been developed and demonstrated with high affinity, specificity, and neutralizing potency. HBV neutralizing antibodies may play a potentially significant role in the search for an HBV cure. In this review, we will summarize the recent progress in developing HBV-neutralizing antibodies, describing their characteristics and potential clinical applications. HBV neutralizing antibodies could be a promising alternative in the prevention and treatment of HBV infection. More importantly, global collaboration and coordinated approaches are thus needed to facilitate the development of novel therapies for HBV infection.

Liver chimeric mice with tupaia hepatocyte transplantation as an animal model for hepatitis B virus infection and antiviral therapy

The human liver chimeric mouse is a milestone animal model for hepatitis B virus (HBV) infection. Such mice with primary human hepatocyte (PHH) transplantation are adequate to support chronic HBV infection for several weeks and to evaluate antiviral drugs. However, the drawbacks of PHHs include lack of available donors, poor expansion in vitro and ethical issues that limit the application of human liver chimeric mice, necessitating the search for alternatives. Here, we transplanted primary tupaia hepatocytes (PTHs) into the livers of immunodeficient mice and achieved high liver chimerism within six weeks. These tupaia liver chimeric mice are adequate to support chronic infection of the four common HBV genotypes A, B, C and D for 36weeks, as well as evaluate of antiviral drugs, including hepatitis B immune globulin (HBIG), monoclonal antibody and nucleoside analogues (NAs), for preventative therapy and treatment post infection. In conclusion, the tupaia liver chimeric mouse model provides a convenient, efficient and stable animal model for chronic HBV infection and long-term drug evaluation.

Real-world efficacy of immunoprophylaxis against mother-to-infant transmission of hepatitis B virus based on puerperant population

Objective To assess the efficacy of immunoprophylaxis against mother-to-infant transmission of hepatitis B virus (HBV) in a real-world setting since the implementation of charge-free hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine in China. Methods The screening rate and the prevalence of hepatitis B surface antigen (HBsAg) in 61 790 puerperants, and the administration of combined immunoprophylaxis in infants of HBsAg-positive mothers in Rugao City of Jiangsu Province from July 1, 2011 to June 30, 2016 were retrospectively analyzed. HBV infection status of infants born to HBV infected mothers was followed up after 7 months of age. HBsAg-positive infants and their mothers were followed up again for HBV markers in April 2018. Fisher's exact test and Cochran-Armitage trend test were used to statistically analyze the differences between groups and various years, respectively. Results All 61 790 puerperants were screened for HBsAg and the prenatal screen rate was 98.6% (60 937/61 790) with an increasing trend over time (χ2trend=750.908, P<0.001). HBsAg-positive puerperants accounted for 5.5% (3 397/61 790) with a decreasing trend over time (χ2trend=32.667, P<0.001). In total, 778 offspring (399 boys and 379 girls) of 759 HBsAg-positive mothers were followed up at (13.7±6.9) months of age, among which 751 (96.5%) were administered and 25 (3.2%) were probably administered standard combined immunoprophylaxis after birth, and the rest two (0.3%) were not. Fourteen infants (1.8%) were HBsAg positive and all born to mothers with positive hepatitis B e antigen (HBeAg). None of the 538 infants born to HBeAg-negative mothers was HBsAg-positive. HBsAg-positive rate in infants born since 2013 was lower than those in 2011 and 2012 (χ2trend=13.352, P=0.000 3). Eleven HBsAg-positive mothers and their children were followed up again 4–5 years later in April 2018. HBV DNA levels of all mothers were within the range of (7.34–28.2)×107 IU/ml except one case of spontaneous HBeAg seroconversion. One out of the 11 infected children also had HBeAg seroconversion. Phylogenetic analysis of HBV S gene showed that the 11 pairs of mothers and children were all infected with HBV of genotype C. Conclusions The implementation of charge-free HBIG and hepatitis B vaccine for newborns achieves fruitful results in Rugao city as the mother-to-infant transmission of HBV in the real-world had been further reduced to a similar level reported in literature survey. Key words: Hepatitis B virus; Hepatitis B; Infectious disease transmission, vertical; Immunoglobulins; Communicable disease control

Reduced Mother-to-Child Transmission of Hepatitis B after Implementation of Completely Charge-Free Immunoprophylaxis in Mainland China

Background: Passive-active immunoprophylaxis with hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine is recommended to prevent mother-to-child transmission (MTCT) of hepatitis B virus (HBV). China has taken a policy to provide charge-free HBIG for infants of HBV-infected mothers since July 2011. We analyzed HBV infection rate in children of HBV-infected mothers born before and since July 2011 in real-life practice. Methods: Totally 5149 children of 5004 HBV-infected mothers, 1160 children born before July 2011 and 3989 children born since July 2011, across Jiangsu province, China, were followed up for HBV markers at 0⋅6-8 years age from 2009 to 2018. Findings: Totally 92 children were HBsAg positive, with an overall infection rate 1⋅79%. MTCT occurred in 0% of 3716 children of hepatitis B e antigen (HBeAg)-negative mothers, and in 6⋅42% of 1433 children of HBeAg-positive mothers (p<0⋅0001). Among 1433 children of HBeAg-positive mothers, transmission occurred in 10⋅27% born before July 2011 and 5⋅5% born since July 2011 (p=0⋅0221); HBIG and vaccine were timely administered in 76⋅47% and 92⋅67% of children born before July 2011 respectively, and in 98⋅02% and 98⋅32% of those born since July 2011 respectively (each p<0⋅0001). Among 1433 children of HBeAg-positive mothers, MTCT occurred in 75 (5⋅54%) of 1355 children with recommended immunoprophylaxis, and in 17 (21⋅79%) of 78 children not per recommended immunoprophylaxis (p<0⋅0001). The lowest HBV DNA level associated with transmission was 3⋅08ₓ106 IU/mL. Interpretation: In addition to maternal HBeAg positive, inappropriate administration of HBIG and/or hepatitis B vaccine is a critical risk for MTCT of HBV in children of HBV-infected mothers. Implementation of charge-free HBIG in infants of HBsAg-positive mothers greatly reduces transmission of HBV. Maternal HBeAg negative or HBV DNA ≤106 IU/mL requires no other interventions to prevent MTCT. Funding Statement: This study was supported by the National Health Commission of China (National Key Clinical Research Project 2011271), the National Natural Science Foundation of China (81672002), the Jiangsu Provincial Health Commission (H201537, XK201607), and the Science and Technology Department of Jiangsu Province (BK20161105), China. Declaration of Interests: The authors declare no conflict of interest. Ethical Approval Statement: The present study was approved by the institutional review board of ethics committee in each hospital. Written informed consent was from the mothers or guardians, who also signed the informed consent for children.

Study of the distribution of hepatitis B immunoglobulin in pregnant mice using small-animal imaging technology.

The safety and necessity of hepatitis B immunoglobulin (HBIG) in preventing the mother-to-child transmission of hepatitis B virus (HBV) are still controversial because of its unclear mechanism of action and the inconsistent injection programs used during gestation. This study aimed to show the dynamic transportation and distribution of HBIG in the maternal body and to provide evidence for its clinical efficacy in preventing mother-to-child HBV transmission. Pregnant mice were injected with Cy7-labeled mouse anti-human monoclonal hepatitis B surface antibodies through the tail vein. In vivo imaging technology was used to observe the dynamic transportation and distribution of HBIG in the pregnant mice. HBIG fluorescence signals were higher in the uterus than in the liver, spleen, and kidneys. Fluorescence signals in the uterine region were obviously higher at the third trimester than at early and mid pregnancy. HBIG is gradually deposited in the mouse placenta during pregnancy, with the phenomenon being more significant in the third trimester.