BACKGROUND: In endemic areas, vertical transmission of hepatitis B virus (HBV) remains a major source of the global reservoir of infected people. Eliminating mother-to-child transmission (MTCT) of HBV is at the heart of World Health Organization\'s goal of reducing the incidence of HBV in children to less than 0.1% by 2030. Universal screening for hepatitis B during pregnancy and neonatal vaccination are the main preventive measures.
OBJECTIVE: To evaluate the efficacy of HBV vaccination combined with one dose of immunoglobulin in children born to hepatitis B surface antigen (HBsAg)-positive mothers in Djibouti city.
METHODS: We conducted a study in a prospective cohort of HBsAg-positive pregnant women and their infants. The study ran from January 2021 to May 2022, and infants were followed up to 7 mo of age. HBV serological markers and viral load in pregnant women were measured using aVidas microparticle enzyme-linked immunosorbent assay (Biomérieux, Paris, France) and the automated Amplix platform (Biosynex, Strasbourg, France). All infants received hepatitis B immunoglobulin and were vaccinated against HBV at birth. These infants were closely monitored to assess their seroprotective response and for failure of immunoprophylaxis. Simple logistic regression was also used to identify risk factors associated with immunoprophylaxis failure and poor vaccine response. All statistical analyses were performed with version 4.0.1 of the R software.
RESULTS: Of the 50 pregnant women recruited, the median age was 31 years, ranging from 18 years to 41 years. The MTCT rate in this cohort was 4% (2/50) in HBsAg-positive women and 67% (2/3) in hepatitis B e antigen-positive women with a viral load > 200000 IU/mL. Of the 48 infants who did not fail immunoprophylaxis, 8 (16%) became poor responders (anti-HB < 100 mIU/mL) after HBV vaccination and hepatitis B immunoglobulin, while 40 (84%) infants achieved a good level of seroprotection (anti-HB > 100 mIU/mL). Factors associated with this failure of immunoprophylaxis were maternal HBV DNA levels (> 200000 IU/mL) and hepatitis B e antigen-positive status (odds ratio = 158, 95% confidence interval: 5.05-4958, P < 0.01). Birth weight < 2500 g was associated with a poor immune response to vaccination (odds ratio = 34, 95% confidence interval: 3.01-383.86, P < 0.01).
CONCLUSIONS: Despite a failure rate of immunoprophylaxis higher than the World Health Organization target, this study showed that the combination of immunoglobulin and HBV vaccine was effective in preventing MTCT of HBV. Therefore, further studies are needed to better understand the challenges associated with immunoprophylaxis failure in infants in Djibouti city.

UNASSIGNED: The utility of hepatitis B immunoglobulin (HBIg) in hepatitis D virus (HDV)-reactivation prophylaxis remains contentious. This study compared liver transplant (LT) patients based on whether they received perioperative HBIg to assess its protective effect against HDV reactivation.
UNASSIGNED: Fifty-seven recipients with hepatitis B virus (HBV) and HBV/HDV, who were at least 1 year posttransplantation as of January 1, 2021, were enrolled in this single-center study. Tests for hepatitis B surface antigen (HBsAg), anti-HDV antibody, and quantitative reverse transcription polymerase chain reaction for HBV DNA and HDV RNA were performed. Interviews were conducted to assess compliance with the nucleos(t) ide analogue (NA) regimen and to document preoperative HBV/HDV status. Liver function tests were also carried out. The nonparametric Mann-Whitney U-test was utilized to determine statistical significance, with P<0.05 considered significant. Data analysis was conducted using GraphPad Prism software.
UNASSIGNED: The prevalence of HDV RNA, HBV DNA, HBsAg, and anti-HDV positivity in the HBIg group (n=23) was 4.3% (n=1), 17.4% (n=4), 8.7% (n=2), and 95.7% (n=22), respectively. In the non-HBIg group (n=34), these rates were 5.9% (n=2), 8.8% (n=3), 11.8% (n=4), and 97.1% (n=33), respectively. Interviews revealed that all reactivations occurred in patients who were noncompliant with their NA regimen. Eleven of the 13 patients initially reported to be monoinfected with HBV pretransplantation were anti-HDV-positive.
UNASSIGNED: No HDV replication occurred in either group due to spontaneous reactivation. High-efficacy NAs appear to be effective in sustaining HDV suppression post-LT. Most recrudescent cases of chronic hepatitis D are mild and self-limiting, typically resolving after 1-2 years of replication, as evidenced by liver function tests.

Objective: To observe the recurrence condition of hepatitis B in different risk groups after liver transplantation in an attempt to provide useful information on whether to discontinue hepatitis B immunoglobulin (HBIG) in the future at an early stage. Methods: The patient population was divided into high, low-risk, and special groups [especially primary hepatocellular carcinoma (HCC)] according to the guidelines for the prevention and treatment of hepatitis B recurrence after liver transplantation. The recurrence condition and risk factors in this population were observed for hepatitis B. Measurement data were analyzed using a t-test and a rank-sum test. Count data were compared using a χ(2) test between groups. Results: This study finally included 532 hepatitis B-related liver transplant cases. A total of 35 cases had HBV recurrence after liver transplantation, including 34 cases that were HBsAg positive, one case that was HBsAg negative, and 10 cases that were hepatitis B virus (HBV) DNA positive. The overall HBV recurrence rate was 6.6%. The recurrence rate of HBV was 9.2% and 4.8% in the high- and low-risk HBV DNA positive and negative groups before surgery (P = 0.057). Among the 293 cases diagnosed with HCC before liver transplantation, 30 had hepatitis B recurrence after surgery, with a recurrence rate of 10.2%. The independent related factors for the recurrence of hepatitis B in patients with HCC after liver transplantation were HCC recurrence (HR =181.92, 95%CI 15.99~2 069.96, P < 0.001), a high postoperative dose of mycophenolate mofetil dispersible tablets (MMF) ( HR =5.190, 95%CI 1.289~20.889, P = 0.020), and a high dosage of HBIG (HR = 1.012, 95%CI 1.001~1.023, P = 0.035). Among the 239 cases who were non-HCC before liver transplantation, five cases (recurrence rate of 2.1%) arouse postoperative hepatitis B recurrence. Lamivudine was used in all cases, combined with on-demand HBIG prophylaxis after surgery. There was no hepatitis B recurrence in non-HCC patients who treated with entecavir combined with HBIG after surgery. Conclusion: High-barrier-to-resistance nucleotide analogues combined with long-term HBIG have a good effect on preventing the recurrence of hepatitis B after liver transplantation. The discontinuation of HBIG may be considered at an early stage after administration of a high-barrier-to-resistance nucleotide analogue in low-risk patients. Domestically, the HBV infection rate is high, so further research is still required to explore the timing of HBIG discontinuation for high-risk patients, especially those with HCC.
目的： 观察不同风险人群在肝移植术后乙型肝炎的复发情况，为以后是否早期停用乙型肝炎免疫球蛋白(HBIG)提供有用信息。 方法： 根据肝移植术后乙型肝炎复发防治指南分为高、低风险人群及特殊人群[尤其原发性肝细胞癌(HCC)]，观察这部分人群乙型肝炎复发情况及复发的危险因素。计量资料组间比较采用t检验、秩和检验；计数资料组间比较采用χ(2)检验。 结果： 最终纳入532例乙型肝炎相关肝移植患者。肝移植术后共35例出现HBV复发，其中HBsAg阳性34例，HBsAg阴性1例，乙型肝炎病毒(HBV) DNA阳性10例。乙型肝炎总的复发率为6.6%。术前HBV DNA阳性的高风险人群乙型肝炎的复发率为9.2%，HBV DNA阴性低风险人群的复发率为4.8% (P = 0.057)。肝移植术前诊断为HCC的293例患者中术后30例出现乙型肝炎复发，复发率为10.2%。HCC患者肝移植术后乙型肝炎复发的独立相关因素为HCC复发(HR = 181.92, 95%CI 15.99～2 069.96, P < 0.001)、术后吗替麦考酚酯分散片(MMF)剂量高(HR = 5.190, 95%CI 1.289～20.889, P = 0.020)和HBIG用量大(HR = 1.012, 95%CI 1.001～1.023, P = 0.035)。肝移植术前非HCC的239例患者中5例患者出现术后乙型肝炎复发(复发率为2.1%)，均为术后应用拉米夫定联合按需HBIG预防治疗的患者，术后恩替卡韦联合HBIG的非HCC患者没有乙型肝炎复发。 结论： 肝移植术后高耐药屏障核苷酸类似物联合长期HBIG预防乙型肝炎复发效果好。对于低风险患者给予高耐药屏障核苷酸类似物后可考虑早期停用HBIG；对于高风险患者，特别是HCC的高风险患者，国内HBV感染率高，尚需进一步研究探索HBIG停药时机。.

Recommended post-liver transplant (LT) prophylaxis in patients with hepatitis delta includes a nucleos(t)ide analogue (NA) and anti-hepatitis B immunoglobulin (HBIG) indefinitely. We analysed the use of HBIG in real-life clinical practice and its impact on HBV/HDV recurrence in 174 HDV-related LT patients from 10 Spanish liver transplant centres (1988-2018). Median post-LT follow-up was 7.8 (2.3-15.1) years and patient survival at 5 years was 90%. Most patients (97%) received HBIG in the immediate post-LT, but only 42% were on HBIG at the last control. Among those discontinuing HBIG, the median time on treatment was 18 (7-52) months. Post-LT HBsAg+ was detected in 16 (9%) patients and HBV-DNA in 12 (7%). Despite HBsAg positivity, HDV recurrence was reported only in three patients (1.7%), all of whom were not receiving NA and had discontinued HBIG. Our data suggest that a finite HBIG prophylaxis in HDV-LT is feasible, especially if high-barrier NAs are used.

This study aimed to establish a second national standard for hepatitis B immunoglobulin (HBIG) that can be used for potency assays of hepatitis B and normal immunoglobulin. The candidate material was manufactured using a process approved as Good Manufacturing Practice. The freeze-dried candidate preparation was tested for physicochemical and biological properties, including pH, residual moisture, molecular size distribution, and potency. A collaborative study was performed involving four laboratories, including the National Institute of Food and Drug Safety Evaluation, as an official national control laboratory in Korea and manufacturers. The potency was calibrated against the second international standard for HBIG using two enzyme immunoassays: enzyme-linked immunosorbent assay and electrochemiluminescence immunoassay. Results from 240 assays were obtained from four laboratories, and combined potency estimates were obtained by calculating the geometric means. Intra- and inter-laboratory variability showed acceptable geometric coefficients of variation of 1.3-6.0 and 3.2-3.6%, respectively. The candidate preparation showed satisfactory stability in accelerated thermal degradation and real-time stability tests. Based on these results, the potency value of 105 IU/vial was assigned (95% confidence intervals: 100.0-109.2 IU/vial), and it was deemed suitable to serve as the Korean national standard for HBIG.

The extent to which maternal antibodies against the hepatitis B surface antigen (HBsAb) acquired transplacentally affect the immune responses to the hepatitis B vaccine (HBVac) in infants is still uncertain.
To explore the impact of the HBsAb on the immune response to the HBVac in a mouse model.
According to the doses of the HBVac (2, 5 μg) injected, 267 BALB/c mice were divided into two groups. Each group was subdivided into 3 subgroups based on the doses of the hepatitis B immunoglobulin (HBIG) (0, 25, 50 IU) administered. The HBsAb titers were detected 4 weeks after completing the HepB vaccination.
Among all the mice, 40 had an HBsAb titer <100 mIU/mL (non- or low-response to the HBVac). The rates of the HBsAb titer <100 mIU/mL in 0, 25 and 50 IU HBIG groups were 1.1%, 23.1%, and 20.7%, respectively. Multivariate logistic regression analysis showed that the risk factors for low- or non-response to the HBVac were injection with the HBIG, low HBVac dose, and hypodermic injection. The mean HBsAb titers (log10) reduced gradually in the 0, 25 and 50 IU HBIG groups (P<0.001).
The HBIG administration has negative impacts on the peak level of the HBsAb and the rate of an effective immune response. This implies that the maternal HBsAb acquired transplacentally might inhibit the immune responses to the HBVac in infants.

UNASSIGNED: Vertical mother-to-child transmission (MTCT) of the hepatitis B virus (HBV) remains an important issue. Timely administration of hepatitis B immunoglobulin (HBIG) and of the HBV vaccine is effective in preventing MTCT in infants born to HBV-infected mothers. However, HBIG is often not easily available in low-income countries or regions.
UNASSIGNED: We compared in a retrospective cohort study the HBV vaccine efficacy alone and in combination with HBIG in preventing vertical MTCT in infants born to HBeAg-negative carrier mothers in Jiangsu province, China. Based on the administration of the HBV vaccine and HBIG shortly after birth, children were divided into two groups: Group 1, administration of the HBV vaccine alone, and Group 2, concurrent use of HBIG and of the HBV vaccine.
UNASSIGNED: A total of 620 infants born to HBeAg-negative carrier mothers were enrolled into this study. Group 1 included 195 children who had received the HBV vaccine alone after birth, and Group 2, 425 children who had received both HBIG and the HBV vaccine. Children were followed up to the age of 68 and 42 months, respectively. MTCT of HBV occurred in 0% (0/195) in Group 1 (HBV vaccine alone) and 0% (0/425) in Group 2 (HBV vaccine and HBIG) (p = 1.00).
UNASSIGNED: In this retrospective cohort study, we found that HBV vaccination alone shortly after birth was effective in preventing MTCT of HBV in infants born to HBeAg-negative carrier mothers.

The significant morbidity and mortality of people with end-stage renal, liver, heart, and lung diseases in need of transplantation provides rationale for use of organs from donors who are hepatitis B positive. The recipient\'s hepatitis B status plays a key role in defining the prophylactic strategy. The availability of safe and effective therapies (hepatitis B antivirals and hepatitis B immune globulin) has contributed to the safety of using hepatitis B-positive donors. The outcomes in both liver and nonliver solid organ transplant recipients given hepatitis B-positive organs have been excellent if appropriate prophylactic therapies provided.

Hepatitis B core antibody (anti-HBc)-positive donors are used as an extended donor pool, and current guidelines recommend the usage of nucleos(t)ide analogues (NAs) as prophylaxis for preventing de novo hepatitis B virus infection (DNH). We analyzed the long-term outcomes of a large cohort of liver transplantation (LT) patients receiving anti-HBc-positive grafts and evaluated the risk of DNH when hepatitis B immunoglobulin (HBIG) monotherapy was used as prophylaxis. We also compared the cost-effectiveness of HBIG and NAs.
We retrospectively reviewed 457 patients with anti-HBc-positive grafts and 898 patients with anti-HBc-negative grafts who underwent LT between January 2001 and December 2018. We compared recipient characteristics according to the anti-HBc status of the donor, and compared the costs of using NAs for the rest of the patient\'s life and using HBIG to maintain hepatitis B surface antibody titers above 200 IU/L.
The 1-, 5-, and 10-year patient survival rates were 87.7%, 73.5%, and 67.7%, respectively, in patients with anti-HBc-positive grafts, and 88.5%, 77.4%, and 70.3%, respectively, in patients with anti-HBc-negative grafts (P=0.113). Among 457 recipients with anti-HBc-positive grafts, 117 (25.6%) were non-HBV recipients. The overall incidence of DNH was 0.9%. When using HBIG under insurance coverage, the cumulative cost was lower compared with using NA continuously without insurance coverage in Korea.
Anti-HBc-positive grafts alone do not affect patient survival or graft survival. HBIG monoprophylaxis has good outcomes for preventing DNH, and the patient\'s long-term cost burden is low in Korea because of the national insurance system in this cohort.

Objectives: China has implemented universal hepatitis B vaccination since 2002 and provided charge-free hepatitis B immunoglobulin (HBIG) to infants of HBV-infected mothers since July 2011. We aimed to compare mother-to-child transmission (MTCT) in children born before and since July 2011.Methods: In total, 5,149 children of HBV-infected mothers were tested for HBV markers. Group one contained 1,160 children born during August 2002-June 2011 and group two contained 3,989 children born during July 2011-June 2016.Results: In total, 92 (1.8%, 95% confidence interval [95%CI] 1.4-2.2) children were infected with HBV. None (0%, 95%CI 0.0-0.1) of 3,716 children of mothers with negative hepatitis B e antigen (HBeAg) was infected, whereas 92 (6.4%, 95%CI 5.2-7.8) of 1,433 children of HBeAg-positive mothers were infected (p < 0.0001). Among children of HBeAg-positive mothers, MTCT occurred in 10.3% (19/185) (95%CI 6.3-15.6) in group one and 5.8% (73/1,248) (95%CI 4.6-7.3) in group two (p = 0.02).Conclusions: Implementing charge-free active-passive immunoprophylaxis greatly reduces MTCT of HBV in children of HBeAg-positive mothers, highlighting the importance of timely administration of both hepatitis B vaccine and HBIG to prevent MTCT. The still remaining MTCT suggests that reducing maternal virus load before delivery is an additional important measure.