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Introduction: Taye and colleagues reported that the rate of mother-to-child transmission (MTCT) of hepatitis B virus (HBV) was as high as 20.7% in Ethiopia based on their meta-analysis of three studies [1]. However, numerous studies demonstrate that the overall rate of MTCT is below 5% after timely neonatal administration of hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine after birth., Concerns: The reports on which the meta-analysis was conducted appear to be problematic. The infants of HBV-infected mothers were not vaccinated against HBV at all, in one report. In another report, MTCT was defined based on positive hepatitis B surface antigen (HBsAg) in the umbilical cord blood, which is not correct because vast majority (> 95%) of positive HBsAg in umbilical cord blood is not infected with, but exposed to, HBV. Thus, MTCT of HBV calculated to be as high as 20.7% in this meta-analysis was overestimated, and much higher than the reported rate of 1-3% immunoprophylaxis failure in other parts of the world, including in Africa., Conclusions: The rate of MTCT of HBV in Ethiopia in this meta-analysis was overestimated. High-quality investigations are required to understand the real picture of immunoprophylaxis against MTCT of HBV in Ethiopia., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Jie Tang, Hong Zhao.)

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.

Background: 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., Objective: To explore the impact of the HBsAb on the immune response to the HBVac in a mouse model., Methods: 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., Results: 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)., Conclusion: 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.

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background/aims: 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., Methods: 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., Results: 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., Conclusion: 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.

The advance in treatment against hepatitis B virus (HBV) infection with the development of nucleos(t)ide analogues (NAs) with high genetic barrier to resistance, including entecavir and tenofovir, has improved clinical outcomes of patients transplanted for HBV infection, by preventing HBV recurrence after liver transplantation (LT) effectively. Currently, after LT, the combination of hepatitis B immunoglobulin (HBIG) and a high-barrier NA is considered as the standard of care for prophylaxis against HBV recurrence. However, because of the high cost of intravenous high-dose HBIG, other routes of HBIG administration, such as intramuscular or subcutaneous, have come to the foreground. In addition, several transplant centres tend to use a NA as monoprophylaxis, following a short post-LT period of HBIG and NA combination. Lately, studies using HBIG-free prophylactic regimens with entecavir or tenofovir have shown promising outcomes in preventing HBV recurrence, mostly regarding patients with undetectable HBV DNA at the time of LT. Although vaccination against HBV has been an attractive prophylactic approach, its efficacy has been controversial. Moreover, further studies are needed regarding long-term outcomes of complete withdrawal anti-HBV prophylaxis. For patients transplanted for HBV/HDV co-infection, combined regimen should be administered for a longer period post-LT. Finally, the use of grafts from hepatitis B core antibody-positive donors is safe for HBV-negative recipients, with the administration of lifelong antiviral prophylaxis., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Prophylaxis 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., Methods: Korean Organ Transplantation Registry (KOTRY) database and additionally collected data (n = 326) were analyzed with special reference to types of HBV prophylaxis., Results: The 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., Conclusion: Combination 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., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2020 The Korean Academy of Medical Sciences.)

Recently, the Society of Infectious Diseases of Chinese Medical Association and Chinese GRADE Center jointly released the "2019 Chinese practice guideline for the prevention and treatment of hepatitis B virus mother-to-child transmission" . We concerned several issues in the Guideline, including the improper citation of some references, no recommendations for some key strategies for the prevention of hepatitis B virus mother-to-child transmission, insufficient or even lack of evidence for some recommendations and others. Based on the principle of academic contention, we present in this article our comments on the Guideline to discuss these issues with the Guideline's authors and readers.

Background: Prophylaxis for hepatitis B virus (HBV) recurrence is essential after liver transplantation (LT) in HBV-associated recipients. This study established an individualized HBV prophylaxis protocol, through optimization of hepatitis B immunoglobulin (HBIG) administration, with application of simulative half-life (SHL)., Methods: This study involved five parts: Part 1 developed the SHL estimation method with 20 patients; Parts 2 and 3 assessed the SHL variability and developed a simulation model to apply SHL in 100 patients; Part 4 validated the simulation model in 114 patients, and Part 5 was a cross-sectional study on the current status of HBIG infusion intervals in 660 patients., Results: In Part 1, infusion of 10,000 IU HBIG induced add-on rise hepatitis B surface antibody (anti-HBs) titer of 5,252.5 ± 873.7 IU/L, which was 4.4% lower than actual measurement. Mean SHL of 20.0 ± 3.7 days was 2.2% longer than actual measurement. In Part 2, the medians of the intra- and inter-individual coefficient of variation in SHL were 13.5% and 18.5%, respectively. Pretransplant HBV DNA load and posttransplant antiviral therapy did not affect SHL. In Part 3, a simulation model was developed to determine the interval of HBIG infusion, by using SHL. In Part 4, all 114 patients were successfully managed with regular HBIG infusion intervals of ≥ 8 weeks, and the interval was prolonged to ≥ 12 weeks in 89.4%, with a target trough anti-HBs titer ≥ 200 IU/L. In Part 5, 47.4% of our patients received HBIG excessively, at a target trough titer of 500 IU/L., Conclusion: SHL estimation using only clinically available parameters seems to be reliably accurate when compared with actual measurements. We believe that SHL estimation is helpful to establish a personalized HBV prophylaxis protocol for optimizing HBIG administration., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2019 The Korean Academy of Medical Sciences.)

The aim of this study was to investigate the efficacy of antepartum administration of three doses of hepatitis B immunoglobulin (HBIG) in interrupting mother-to-child transmission (MTCT) of hepatitis B virus (HBV). In this trial, a total of 728 HBeAg-positive pregnant women with chronic HBV infection who had an HBV DNA level higher than 6log 10  copies/mL were enrolled. They were divided into three groups based on individual preference. Subjects in group A and group B received 200 IU (unit) HBIG and 400 IU (unit) HBIG intramuscularly once a month at the third, second and first month before delivery, respectively. Subjects in the control group (C) received no special treatment. All the infants received passive-active immunoprophylaxis. The HBsAg-positive rate of all infants at 7-12 months of age was 5.1% (37/728). Specifically, the HBsAg-positive rate of infants was comparable in all three groups (5.3% vs 5.1% vs 5%, P = 0.988). No significant difference was found in anti-HBs levels between the infants aged 7-12 months in the three groups (P = 0.469). HBV DNA levels of the umbilical cord blood in the HBV-infected group were higher than those in the uninfected group (5.2 vs 3.4log 10  copies/mL, P < 0.001), and these with family history of HBV infection were also higher (45.9% vs 28.5%, P = 0.034). To conclude, administration of passive-active immunoprophylaxis to infants contributed to effective prevention of the MTCT of HBV; extra antepartum administration of HBIG during pregnancy could not decrease the rate of MTCT or increase the anti-HBs levels of infants born to HBsAg-positive mothers with HBV DNA higher than 6log 10  copies/mL., (© 2019 The Authors Journal of Viral Hepatitis Published by John Wiley & Sons Ltd.)

Background/aim: In this study, the efficiency of using low-dose hepatitis B immunoglobulin (HBIG) plus antiviral treatment according to individual needs has been evaluated in posttransplant hepatitis B virus (HBV) patients., Materials and Methods: We retrospectively evaluated 179 patients who were admitted between 2009 and 2014. Five thousand IU intravenous HBIG was given in the anhepatic phase, and 400 IU/day intramuscular (IM) HBIG was given in the posttransplant period. After HBsAg seroconversion, 400 IU IM HBIG was continued as prophylaxis every two weeks., Results: The average follow-up period was 26 (2–65) months. Seventy patients had hepatocellular carcinoma (HCC). The HBV recurrence was 4.5% in the first year, and 5.8% in the third year. The HBsAg became negative in 11 (2–63) days, and anti-HBs became positive in 9 (1–31) days. HBsAg positivity occurred in 6 patients during the follow-up period. Five of these patients were those who underwent transplantation due to HCC. In 5 of the HCC patients, in whom HBsAg became positive, tumor recurrence was observed after 0.3–9.9 months. HBsAg positivity was more frequently detected in patients with HCC (P = 0.009)., Conclusion: The HBV recurrence should be evaluated as a predictor of the HCC recurrence in patients who were transplanted due to HCC., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Prophylactic measures are used to reduce DNHB after HBsAg-negative patients receive anti-HBc-positive liver grafts. This study investigated the incidence of DNHB and clinical outcomes in pediatric LT recipients under HBIG prophylaxis, with or without hepatitis B vaccination. Between 1995 and 2013, 51 HBsAg-negative pediatric recipients underwent living-donor LT from anti-HBc-positive donors. The median (range) age was 4 (0.1-17) years, 23 (45%) were male, and 71% were negative for both anti-HBc and anti-HBc. During a median follow-up of 12.1 (0.06-19.9) years, 13 (25.4%) developed DNHB; 7 of the 13 achieved HBsAg seroconversion after administration of LAM or ETV. Among studied patients, 20 (39%) received hepatitis B vaccination, and 2 of them (10%) developed DNHB. At last follow-up, 41% (21/51) discontinued HBIG either after successful HBV vaccination (n = 17) or retransplantation with anti-HBc-negative grafts (n = 4). In conclusion, pediatric LT recipients of anti-HBc-positive grafts, most of them were naïve to HBV infection, were at high risk of DNHB, and consistent monitoring for the early detection of DNHB was necessary. A combination use of post-LT vaccination is promising prophylactic strategy against DNHB., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

To eliminate viral hepatitis as a public health threat, the World Health Organization has set the ambitious goal of reducing the prevalence of hepatitis B surface antigen (HBsAg) in children to 0.1% by 2030, and the key to this grand goal is cutting off hepatitis B virus (HBV) transmission from mother-to-child. Previously, national and international guidelines for the management of chronic hepatitis B recommended the use of hepatitis B vaccine and hepatitis B immunoglobulin (HBIG) or combination of any in neonates and antiviral drugs for pregnant women with high viral load in late pregnancy. However, a recent study in Thailand found that the addition of antiviral drugs in pregnant women with high viral load in the third trimester did not significantly lower the incidence of mother-to-child HBV transmission, but no case of chronic HBV infection was seen with strict standards hepatitis B vaccine and HBIG combined immunoprophylaxis and the use of tenofovir disoproxil in pregnant women with high viral load in the third trimester. In addition, the incidence of mother -to- child transmission of HBV in the antiviral group was 0, while the incidence of HBV transmission in the placebo group was 2%. Therefore, it is not possible to deny the efficacy of adding antiviral drugs in treating pregnant women with high viral load in the third trimester with combined immunoprophylaxis. There is an urgent need for more real-world studies in clinical practice to further reveal the principles and existing problems of mother- to- child transmission of HBV.

Background/aims: A birth dose of hepatitis B immunoglobulin (HBIG), in combination with hepatitis B vaccine (HepB), is recommended for infants born to hepatitis B surface antigen (HBsAg)-positive mothers. However, the optimal dosage of HBIG remains to be resolved. This prospective cohort study aimed to compare the efficacy of two dosages of HBIG combined with HepB to prevent mother-to-child transmission (MTCT) of HBV., Methods: From 2009 to 2011, we prospectively enrolled mother-infant pairs with positive maternal HBsAg in China. Infants were assigned to receive one dose of 100 IU or 200 IU HBIG within 12 h of birth according to maternal numbering, followed by completion of the 3-dose 10 μg HepB series. At 7 months, post-vaccination serologic testing (PVST) was performed in 545 and 632 infants in 100 IU and 200 IU HBIG groups, respectively, among whom, 451 and 529 were followed up to 12 months., Results: Maternal and birth characteristics were comparable between infants in 100 IU and 200 IU HBIG groups. At 7 months, the rates of perinatal infection were 1.5% (8/545) and 1.9% (12/632) in 100 IU and 200 IU HBIG groups, respectively (p = .568). One non-responder infant in 200 IU HBIG group became newly infected at 12 months. The antibody to hepatitis B surface antigen (anti-HBs) positive rates were 98.5% (529/537) and 98.2% (609/620) in 100 IU and 200 IU HBIG groups at 7 months, respectively (p = .704), and the corresponding figures were 98.2% (431/439) and 97.1% (496/511) at 12 months (p = .266). The anti-HBs geometric mean concentrations were comparable between two groups at 7 months (707.95 mIU/mL vs. 602.56 mIU/mL, p = .062) and 12 months (245.47 mIU/mL vs. 229.09 mIU/mL, p = .407)., Conclusions: One birth dose of 100 IU HBIG, combined with the HepB series, might be enough for preventing MTCT of HBV in infants born to HBsAg-positive mothers., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The prevalence of occult hepatitis B virus (HBV) infection (OBI) in children due to mother-to-child transmission (MTCT) despite immunoprophylaxis remains controversial and is still unknown in Japan. The aim of this study was to determine the OBI prevalence in such children in Japan and identify the genomic mutations that might be associated with the pathogenesis of OBI in children., Methods: The data on 158 children born to HBV carrier mothers and who received complete passive-active immunoprophylaxis after birth in 2002-2014 were reviewed. HBV markers were detected using commercial enzyme-linked immunosorbent assay kits. HBV-DNA was detected using real-time and nested polymerase chain reaction. Complete genomic sequences were determined., Results: Among the 158 children studied, three had HBV MTCT: two had OBI, and one had resolved HBV infection (RBI). The prevalence of OBI and RBI was estimated to be 1.3% and 0.6%, respectively. The HBV genomes of the two OBI children were wild type and 100% identical to those of their mothers. Of these two children, one received repeated hepatitis B immunoglobulin (HBIG) and developed overt HBV infection. Her HBV genome had a G145R mutation in the S gene that might have been induced by HBIG treatment. The RBI child was persistently positive for antibody to HBV core antigen (10-12 signal/cut-off ratio; S/CO)., Conclusions: A low prevalence of OBI was observed in children who received immunoprophylaxis for preventing MTCT in Japan. The development of overt HBV infection in infants with OBI indicates the necessity of close and long-term monitoring., (© 2017 Japan Pediatric Society.)

Background and Aim: To prospectively evaluate the efficacy of vaccine alone compared with vaccine plus HBIG for preventing HBV transmission in neonates of HBsAg (+)/HBeAg (-) mothers., Methods: Combined immunization is currently recommended for neonates of HBsAg (+) mothers in China. As a result, a randomized design is infeasible due to ethical reasons. In practice, Guangxi Zhuang Autonomous Region and Jiangsu Province implement vaccine alone and vaccine plus HBIG strategies for neonates born to HBsAg (+)/HBeAg (-) mothers, respectively. We alternatively enrolled neonates of HBsAg (+)/HBeAg (-) mothers from these two regions. Three doses of a recombinant yeast-derived hepatitis B vaccine were given at 0, 1 and 6months with or without HBIG at birth., Results: At 7months, sera were collected from 132 neonates in Guangxi Zhuang Autonomous Region and 752 neonates in Jiangsu Province. Baseline characteristics of both mothers and neonates were comparable in the two regions. No differences were revealed regarding the occurrence of perinatal HBV transmission with or without HBIG at birth [0.1% (1/752) vs. 0.0% (0/132), p=1.000]. The anti-HBs response rates were 97.7% (129/132) and 98.5% (740/751) for the neonates with vaccine alone and with HBIG (p=0.758), respectively. Vaccine alone induced a significantly higher anti-HBs GMC as compared to vaccine plus HBIG at 7months of age (1555.3mIU/mL vs. 654.9mIU/mL, p<0.0001). At 12months of age, protective levels of anti-HBs remained in 97.4% (596/612) and 98.3% (118/120) of the neonates receiving and not receiving HBIG, respectively (p=0.771). The neonates receiving combined prophylaxis had a markedly lower anti-HBs GMC (210.7mIU/mL vs. 297.0mIU/mL, p=0.011). Horizontal HBV transmission occurred in none of the successfully immunized neonates for both compared groups at 12months of age., Conclusions: Vaccine alone may be enough for preventing HBV transmission in neonates of HBsAg (+)/HBeAg (-) mothers., (Copyright © 2016. Published by Elsevier Ltd.)

Advent of hepatitis B immunoglobulin (HBIG) as the mainstay of prophylaxis against hepatitis B recurrence after liver transplantation with antiviral drugs has resulted in excellent outcomes for liver transplantation in hepatitis B virus (HBV)-related cirrhosis in the last two decades. However, there is no consensus on a gold standard prophylaxis protocol and several controversies over the duration, dose, and route of administration of HBIG with or without different antivirals exist among liver transplantation centers. We present this review of different prophylaxis regimens including HBIG and antiviral monotherapy, combination of HBIG with antivirals, and withdrawal of HBIG and whole prophylaxis. HBIG monotherapy in either the intramuscular or the subcutaneous form is an accepted choice for prevention of HBV re-infection after liver transplantation in low risk patients. Withdrawal of HBIG monotherapy may be considered but should only occur after transitioning to an oral antiviral therapy such as adefovir, tenofovir, or entecavir. Lamivudine monotherapy may be associated with a higher recurrence rate compared to more potent antivirals. In high risk patients, intramuscular or subcutaneous HBIG in combination with an antiviral, most commonly lamivudine, is currently considered the standard of care. Complete discontinuation of all preventative therapy cannot be recommended at this time and should only be performed in the setting of a clinical trial.

Historically, hepatitis B virus (HBV) liver transplantation (LT) recipients have less acute cellular rejection (ACR) than those without HBV. We questioned whether this has persisted in an era of decreased Hepatitis B immunoglobulin use (HBIG) given its in vitro immunoregulatory effects. We compared the incidence, risk factors and outcomes of ACR among 40,593 primary LT recipients with HBV, hepatitis C, steatohepatitis, and immune liver disease (OPTN 2000-2011). We also assessed the in vitro effect of HBIG on alloimmune lymphoproliferation and regulatory T cell generation using mixed lymphocyte reactions. In multivariate analysis, HBV status remained a strong independent predictor of freedom from ACR (OR 0.58, 95% CI: 1.5-2.1). Patient (67.7% vs 72.3%) and graft (60.8% vs 69.1%) survival were significantly lower in patients with ACR versus no ACR for all causes except HBV. HBIG use had no statistical association with ACR. In vitro, HBIG at concentrations equivalent to clinical dosing did not inhibit lymphoproliferation or promote regulatory T cell development. In summary, the incidence and impact of ACR is lower now for HBV LT and does not appear to be secondary to HBIG by our in vitro and in vivo analyses. Rather, it may be due to the innate immunosuppressive properties of chronic HBV infection., (Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Hepatitis B virus (HBV) infection causes long-term, life-threatening liver diseases worldwide. HBV is transmitted through either the horizontal or mother-to-infant route, which is the major route of transmission in endemic areas. Administration of hepatitis B immunoglobulin and hepatitis B vaccine to newborns of infected mothers prevents mother-to-infant transmission. Implementation of a universal hepatitis B vaccination program has proven successful in eliminating the infection and related complications. Nevertheless, efforts are still needed to improve global coverage of the hepatitis B vaccine. Infants born to highly viremic mothers are still at risk of infection despite current immunoprophylaxis. An increasing number of reports have shown promising efficacy and safety profiles with the use of nucleoside/nucleotide analogues in highly viremic pregnant women to prevent mother-to-infant transmission.

Background & Aims: Hepatocellular carcinoma (HCC) has become a major cause of liver-related death and indication to liver transplantation (LT) in patients with chronic hepatitis B virus (HBV) infection following the widespread adoption of antiviral therapy with nucleos(t)ide analogs (NUCs). Yet, the long-term outcome of patients undergoing liver transplantation for an HCC developed during effective NUC treatment is unknown., Methods: We evaluated 101 patients with persistently compensated cirrhosis who were consecutively transplanted for HCC in two centers in Milan. At LT, 91 (90%) patients had undetectable serum HBV DNA (<12 IU/ml) and 90 (89%) were within Milan criteria (MC). All patients received post-transplant HBV prophylaxis with specific immunoglobulins (HBIgs) and NUCs. End-points were long-term patient survival and recurrence of HCC and HBV., Results: During 106 (range 3-165) months following LT, HCC recurred in 11 (11%) patients (nine beyond MC at explant, two with HBV recurrence). Age (HR 1.1, 95%CI 1.0-1.2, P = 0.04) and exceeding MC (HR 9.6, 95%CI 2.9-32, P < 0.0001) were the only independent pretransplant predictors of tumour recurrence. The 10-year cumulative rate of HCC recurrence was 7% among patients transplanted within MC compared with 45% among those beyond MC at LT (P = 0.004). Overall, 18 patients (18%, nine HCC, nine non liver-related events) died with a 10-year cumulative probability of overall and liver-related survival of 79% and 89% respectively., Conclusions: Extended survival of HBV cirrhotics transplanted for HCC can be achieved by coupling MC at listing with persistent pharmacological suppression of HBV., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: The traditional regimen for prophylaxis of hepatitis B recurrence post-liver transplantation is to use hepatitis B immune globulin (HBIG) along with oral antiviral therapy; however, it is unclear when it is safe to discontinue HBIG after certain time point and to maintain patients with only oral antiviral therapy. Several studies have suggested that maintenance with oral anti-hepatitis B virus (HBV) therapy following short-term or no HBIG following the immediate post-transplantation period may also be safe and effective in prevention of HBV recurrence., Areas Covered: We reviewed relevant literature to determine the effectiveness of early withdrawal of HBIG after liver transplantation and its effect on prevention of HBV recurrence. We used PubMed to search for any studies that used HBIG-free or short-term HBIG protocols with continued anti-HBV therapy. Short-term is defined as 12 months or less, and it is an evolving concept as new data on shorter and shorter duration becomes available. Additionally, a mini-quantitative analysis of the studies was performed using studies that involved the use of entecavir and tenofovir as anti-HBV therapy with or without HBIG., Expert Opinion: Patients who are considered low risk for HBV recurrence at the time of liver transplant may safely be able to utilize a short-term duration of HBIG with indefinite antiviral maintenance therapy afterwards, whereas high-risk patients will likely need long-term HBIG in combination with antiviral therapy.

Liver transplantation is the only effective treatment for hepatitis B virus (HBV)-related end-stage liver disease. However, without antiviral prophylaxis, the recurrence rate of hepatitis B is as high as 80%-100%, which leads to a 50% mortality rate in the first 2 years after liver transplantation. Combination therapy of hepatitis B immunoglobulin (HBIG) and lamivudine demonstrated a higher efficacy of prophylaxis and further reduced the rate of recurrence to < 10%. The strategy of HBIG combined with lamivudine has been the standard treatment in many centers. However, the high rate of lamivudine resistance and the many disadvantages of HBIG have compelled surgeons to reconsider the long-term efficacy of this strategy for the prevention of HBV reinfection. Recently, new nucleos(t)ide analogues, such as entecavir and tenofovir, have been approved as first-line monotherapies for the treatment of chronic hepatitis B infection. These antiviral medicines have replaced lamivudine as the first choice in the prevention of HBV recurrence after liver transplantation. Various therapies that are composed of entecavir, tenofovir, and lamivudine plus adefovir, with or without HBIG have been adopted in several liver transplant centers. This article reviews the recent advances in prophylaxis for the recurrence of hepatitis B after liver transplantation.

Aim: To evaluate the prophylactic efficacy of hepatitis B immunoglobulin (HBIG) in combination with different nucleos(t)ide analogues., Methods: A total of 5333 hepatitis B surface antigen-positive patients from the China Liver Transplant Registry database were enrolled between January 2000 and December 2009. Low-dose intramuscular (im) HBIG combined with one nucleos(t)ide analogue has been shown to be very cost-effective in recent reports. Hepatitis B virus (HBV) prophylactic outcomes were compared based on their posttransplant prophylactic protocols [group A (n = 4684): im HBIG plus lamivudine; group B (n = 491): im HBIG plus entecavir; group C (n = 158): im HBIG plus adefovir dipivoxil]. We compared the related baseline characteristics among the three groups, including the age, male sex, Meld score at the time of transplantation, Child-Pugh score at the time of transplantation, HCC, pre-transplantation hepatitis B e antigen positivity, pre-transplantation HBV deoxyribonucleic acid (HBV DNA) positivity, HBV DNA at the time of transplantation, pre-transplantation antiviral therapy, and the duration of antiviral therapy before transplantation of the patients. We also calculated the 1-, 3- and 5-year survival rates and HBV recurrence rates according to the different groups. All potential risk factors were analyzed using univariate and multivariate analyses., Results: The mean follow-up duration was 42.1 ± 30.3 mo. The 1-, 3- and 5-year survival rates were lower in group A than in groups B (86.2% vs 94.4%, 76.9% vs 86.6%, 73.7% vs 82.4%, respectively, P < 0.001) and C (86.2% vs 92.5%, 76.9% vs 73.7%, 87.0% vs 81.6%, respectively, P < 0.001). The 1-, 3- and 5-year posttransplant HBV recurrence rates were significantly higher in group A than in group B (1.7% vs 0.5%, 3.5% vs 1.5%, 4.7% vs 1.5%, respectively, P = 0.023). No significant difference existed between groups A and C and between groups B and C with respect to the 1-, 3- and 5-year HBV recurrence rates. Pretransplant hepatocellular carcinoma, high viral load and posttransplant prophylactic protocol (lamivudine and HBIG vs entecavir and HBIG) were associated with HBV recurrence., Conclusion: Low-dose intramuscular HBIG in combination with a nucleos(t)ide analogue provides effective prophylaxis against posttransplant HBV recurrence, especially for HBIG plus entecavir.

The effect of hepatitis B immunoglobulin (HBIG) on hepatitis B virus (HBV) DNA load and its protective mechanism are not well understood. Twenty-eight hepatitis B surface antigen (HBsAg)-positive pregnant women and their newborns were assigned to an experimental (n = 12) or control group (n = 16) according to whether they received HBIG during pregnancy. HBV DNA load and markers titer of the mothers and newborns were tested. These markers and HBV DNA load in mothers of the experimental group did not fluctuate significantly and were comparable to the control. In the experimental group, there was a positive correlation between mothers and their newborns with regard to hepatitis B surface antibody titer. Immunohistochemical staining of placenta sections showed that HBsAg-positive areas mainly included trophoblastic cells and villous mesenchymal cells without HBIG colocalization, whereas HBIG-positive areas principally included villous capillary endothelial cells and villous mesenchymal cells. Additionally, compared with the control group, the positive rate and mean density of HBIG in the experimental group were remarkably higher. HBIG deposition was seen in Hofbauer cells. Thus, rather than influencing virus replication, HBIG forms an immune barrier between the mother and fetus to prevent HBV transmission.

Objective: We sought to investigate new changes in the clinical pathology of hepatitis B virus (HBV) recurrence after orthotopic liver transplantation (OLT) in era of new nucleoside or nucleotide analogues., Methods: One hundred and eighty-four adult patients who underwent OLT for HBV-related end-stage liver disease between 1999 and 2010 were enrolled in this study. Of these patients, 156 received lamivudine (LAM) plus hepatitis B immune globulin (HBIG) and 28 were treated with LAM. The liver function, serologic parameters and HBV-DNA of the 184 recipients were followed up, and clinical pathological characteristics of grafts with HBV recurrence were examined in this study., Results: One hundred and seventy-nine (97%) were alive at their last follow-up and eleven (6%) had developed HBV recurrence at a median of 22 (range 6 to 46) months post-OLT. Two of the 11 recipients were detected with HBV-S gene mutation, and 5 were tested with YMDD mutation. Four recipients who died of irreversible graft dysfunction secondary to HBV recurrence, developed fibrosing cholestatic hepatitis (FCH) because of no effective antiviral agents available in the early stages of HBV recurrence after OLT. Six recipients who received adefovir (ADV) (and Entecavir, ETV) in the early stages of HBV recurrence after OLT achieved improvement in hepatic histology., Conclusions: HBV recurrence post-OLT could be controlled at an acceptable level for a long time and the recipients could achieve long-term survival by using new antiviral agents, instead of advancing into FCH in the short term after HBV recurrence.

Background and Aim: Without effective prophylaxis, liver transplantation (LT) for hepatitis B virus (HBV)-related liver disease is frequently complicated by severe and rapidly progressive HBV recurrence. The combination of low-dose hepatitis B immunoglobulin (HBIG) and the new nucleos(t)ide analog, entecavir, as prophylaxis for HBV recurrence after living-donor LT (LDLT) were analyzed., Methods: A total of 315 patients with positive hepatitis B surface antigen underwent LDLT at our transplant center between July 2003 and December 2011. Our protocol for post-transplantation HBV prophylaxis was a combination of low-dose HBIG and nucleos(t)ide analog., Results: During a median follow-up period of 49 months post-transplant, 10 patients (3.2%) had HBV recurrence, which was significantly related to hepatocellular carcinoma (HCC) at transplantation (P = 0.041) and post-LT antiviral agent (P < 0.001) in multivariate analysis. The level of HBV DNA and hepatitis B e antigen state at transplantation were not significant factors for HBV recurrence (P = 0.342 and P = 0.802, respectively). In 170 patients with HCC at LDLT, HCC recurrence was significantly related to HBV recurrence (P < 0.001). Among 10 patients with HBV recurrence, three are alive and two had lost hepatitis B surface antigen. The remaining seven patients died of HCC recurrence., Conclusions: The combination of low-dose HBIG and nucleos(t)ide analogs is safe and effective for HBV prophylaxis after LDLT. As a post-LT antiviral treatment, entecavir is more effective than lamivudine. HCC at transplantation was significantly associated with HBV recurrence. HBV-related HCC patients who undergo LDLT require close virological monitoring., (© 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Orthotopic liver transplantation (OLT) is the preferred treatment for selected patients with hepatitis B virus (HBV)-related liver disease. This study aimed to (i) define long-term outcomes following OLT for HBV; (ii) to quantify the incidence of HBV recurrence (rHBV) as it relates to anti-HBV treatment; and (iii) to determine outcomes for specific patient subgroups. We performed a retrospective chart review of 738 patients undergoing OLT between 1985 and 2010 at seven US transplant centers and divided the patients into 3 eras, 1985-1994, 1995-2004, and 2005-2010, based on hepatitis B immunoglobulin and antiviral therapies. In Era 3, female gender (p = 0.002), recurrent hepatocellular cancer (p < 0.001), and retransplantation (p = 0.01) were significantly associated with worse survival on multivariate analysis. Survival at three yr was poor for all ethnicities in Era 1, but significantly improved for all except black Americans by Era 3. Era 2 data showed a continued increase in rHBV from five to 10 yr (16.6%, 26.2%). In conclusion, while OLT outcomes have improved because of combination antiviral and immunoglobulin therapy, women and black Americans may not have realized an equal benefit. The rate of rHBV is significant even 10 yr post-transplant with survival affected., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To develop a guideline for the management of potential exposures to hepatitis B virus (HBV) at The Alfred Hospital, based on results of clinical audit, database analysis and literature review., Methods: i) Retrospective record review of all histories of patients who received HBV immunoglobulin (HBIG) at The Alfred between 1/1/2007 and 30/9/2011. ii) Analysis of HBV serological results of men who have sex with men (MSM) on Victorian NPEP Service (VNPEPS) database between 10/8/2005 and 31/12/2011. iii) Literature review to determine risks of HBV transmission and best practice for prevention of HBV transmission., Results: A total of 48 patients were potentially exposed to HBV and given HBIG, with sexual exposure the most common indication (n=20). The source was reported to be HBsAg positive in one case only. Of the MSM on the VNPEPS database, 63% were immune to HBV, and only 0.5% of patients tested had evidence of chronic HBV infection. The recommendations for use of HBIG in The Australian Immunisation Guidelines are ambiguous and differ from other international guidelines., Conclusion: This audit at a tertiary referral hospital identified problems with the management of those potentially exposed to HBV. In those non-immune patients exposed to HBV, the combination of HBIG plus vaccination provides the best protection against infection. The risk of transmission of HBV is highly variable; rates of chronic HBV in PWID and MSM in Australia are low and do not warrant use of HBIG unless the source is known to be HBsAg positive., (© 2013 The Authors. ANZJPH © 2013 Public Health Association of Australia.)

Background & Aims: Despite appropriate passive and active immunization, perinatal transmission of hepatitis B virus (HBV) still occurs in 5%-10% of infants born to women with high levels of viremia who test positive for the hepatitis B e antigen (HBeAg). We evaluated the effects of cesarean section delivery on perinatal transmission of HBV from women who tested positive for the hepatitis B surface antigen (HBsAg)., Methods: We analyzed data from 1409 infants born to HBsAg-positive mothers through vaginal delivery (VD) (n = 673), elective caesarean section (ECS) (n = 496), or urgent cesarean section (UCS) (n = 240) who completed appropriate immunization against HBV. The prevention was assumed to have failed for infants who were HBsAg positive when they were 7-12 months old; this information was used to assess transmission rates., Results: HBV infection was transmitted to a smaller percentage of infants born by ECS (1.4%) than by VD (3.4%, P < .032) or UCS (4.2%, P < .020). UCS had no effect on vertical transmission, compared with VD (4.2% vs 3.4%, P = .593). Infants born by ECS had a significantly lower rate of vertical transmission than those born by non-ECS (1.4% vs 3.6%, P = .017). Women with HBV DNA levels <1,000,000 copies/mL did not transmit the infection to their infants, regardless of method of delivery. There were no differences in maternal or infant morbidity and mortality among the groups., Conclusions: There is a significantly lower rate of vertical transmission of HBV infection to infants delivered by ECS, compared with those delivered vaginally or by UCS. Elective cesarean sections for HBeAg-positive mothers with pre-delivery levels of HBV DNA ≥1,000,000 copies/mL could reduce vertical transmission., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

We describe the case of transmission of an HBsAg-negative hepatitis B infection to an immunosuppressed patient by plasma donation from an HBsAg-negative subject, but with very low serum HBV DNA (about 50 IU/ml) and five mutations in the major hydrophilic region of HBsAg., (Copyright © 2013. Published by Elsevier B.V.)

Aim: Reactivation of hepatitis B virus (HBV) after liver transplantation (LT) remains a problem; thus, development of more effective HBV reactivation prophylaxis is desirable. We evaluated the efficacy of a combination of a long‐term nucleotide analog (NA), such as entecavir (ETV) or tenofovir alafenamide (TAF), and short‐term hepatitis B immunoglobulin (HBIG) in preventing HBV reactivation and compared it with conventional HBV prophylaxis. Methods: Between February 1999 and August 2023, 135 patients underwent living‐donor liver transplantation for liver cirrhosis or acute liver failure caused by HBV infection or received an LT from a hepatitis B core antibody‐positive donor. Recipients who had undergone LT were classified as being in the first or second era (namely until September 2017 and from October 2017), respectively, and outcomes of prophylaxis against HBV reactivation were compared between the two eras. Results: In the second era, recipients with HBV‐related disease or who had received hepatitis B core antibody‐positive liver received combination therapy with short‐term HBIG and an NA such as TAF and ETV long‐term. The duration of HBIG treatment was markedly shorter than in the first era in both categories of patients and HBIG could be discontinued in all cases. Surprisingly, we observed HBV reactivation in the first era, but not in the second era, in both groups. Conclusions: We have established a protocol for prophylaxis against HBV reactivation using a combination of short‐term HBIG and long‐term NA. This protocol was found to be sufficient to prevent HBV reactivation after LT. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: 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. Objectives: 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. Study design: 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. Results: 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. Conclusions: HBIG is gradually deposited in the mouse placenta during pregnancy, with the phenomenon being more significant in the third trimester. Highlight: Study of the distribution of hepatitis B immunoglobulin. [ABSTRACT FROM AUTHOR]

Bachground: The combinative regimens using oral nucleos(t)ide analogs (NA) plus either regular or on-demand low dose hepatitis B immunoglobulin (HBIG) have shown significant decrease in recurrence of post-liver transplantation (LT) hepatitis B, leading to considerable cost saving. Most of the protocols aimed to maintain hepatitis B surface antibody (HBsAb) levels above 100 IU/mL. Objective: To demonstrate that the maintenance threshold for HBsAb level could be lowered to 50 IU/mL for hepatitis B virus (HBV) prophylaxis during post-LT. Materials and Methods: The authors conducted a retrospective study of 45 patients that undergone LT for HBV-related diseases between 2003 and 2015. All patients had been followed-up and placed on a post-LT anti-HBV regimen of on-demand low-dose HBIG plus NAs. A fixed dose of 800 U HBIG was given as required to maintain HBsAb levels above 50 IU/mL. HBV recurrence was defined as persistent reappearance of HBsAg. Results: The mean follow-up was 57.8±38.3 months (range 6 months to 12 years), and no patient experienced HBV recurrence during that period. However, two patients experienced a few episodes of non-sustained HBsAg seropositivity without active disease, which indicated an actuarial risk of recurrence of 4.4%. The mean level of HBsAb in each stratified period was well maintained above 50 IU/mL. The estimated cost of HBIG was approximately 50% of the cost for the regular low-dose regimen. Conclusion: The present regimen yielded good result and significant cost reduction. The authors propose the maintenance HBsAb level could be reduced to 50 IU/mL without compromising the clinical outcome. [ABSTRACT FROM AUTHOR]

Background: The most common indication for liver transplantation (LT) in South East Asia is hepatitis B virus (HBV)-related liver disease. Without proper prophylaxis, HBV will recur rapidly after LT. Currently, there is no universally accepted regimen, and most transplant centers use high-dose hepatitis B immunoglobulin (HBIG) for prophylaxis, which is costly. Objective: To review the authors' experience with low-dose short-course HBIG plus antiviral for HBV prophylaxis. Materials and Methods: Between July 2002 and December 2013, 90 patients who were positive for HBV surface antigen (HBsAg) underwent LT at the authors' institute. The protocol included continuing previously prescribed antiviral drug or giving lamivudine 150 mg orally before the operation in patients who had never received antiviral drug. All patients received 1,200 to 2,000 international units (IU) of HBIG intravenously during anhepatic phase, and 1,200 to 1,600 IU of intravenous HBIG daily for six days postoperatively. Oral antiviral drug was continued postoperatively. HBV recurrence was defined as the reappearance of HBsAg in serum. Cumulative incidence function was used to calculated cumulative recurrence rate. Results: At the end of follow-up, the post-transplant HBsAg status was positive in six patients (6.7%); two patients at three months, one patient at one year, two patients at seven years, and one patient at ten years after LT. Cumulative HBV recurrence rate was 2.3% at one year, 3.5% at five years, and 11.3% at ten years after LT. The median time-to-recurrence was 49.5 months. All treatments were well tolerated with no serious adverse event. Conclusion: Combination of low-dose short-course HBIG and long-term oral antiviral drug is effective in preventing HBV recurrence after LT. Since HBIG is very expensive, this low-dose short-course HBIG prophylaxis regimen can reduce the cost of LT without increasing the HBV recurrence rate. [ABSTRACT FROM AUTHOR]

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 potency was calibrated against the second international standard for HBIG. • The candidate preparation showed satisfactory stability. • The potency value of 105 IU/vial was assigned. [ABSTRACT FROM AUTHOR]

Hepatitis B often progresses to decompensated liver cirrhosis requiring orthotopic liver transplantation (OLT). Although newer nucleos(t)ide analogues result in >90% viral and hepatitis activity control, severely decompensated patients still need OLT because of drug-resistant virus, acute exacerbation, or hepatocellular carcinoma. Acute hepatitis B is also an indication for OLT, because it can progress to fatal acute liver failure. After OLT, the hepatitis B recurrence rate is >80% without prevention, while >90% of transplant recipients are clinically controlled with combined hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogue treatment. However, long-term HBIG administration is associated with several unresolved issues, including limited availability and extremely high cost; therefore, several treatment protocols with low-dose HBIG, combined with nucleos(t)ide analogues, have been investigated. Another approach is to induce self-producing anti-hepatitis B virus (HBV) antibodies using an HBV envelope (HBs) antigen vaccine. Patients who are not HBV carriers, such as those with acutely infected liver failure, are good candidates for vaccination. For chronic HBV carrier liver cirrhosis patients, a successful vaccine response can only be achieved in selected patients, such as those treated with experimentally reduced immunosuppression protocols. The present protocol for post-OLT HBV control and the future prospects of newer treatment strategies are reviewed. [ABSTRACT FROM AUTHOR]

A combination of hepatitis B immunoglobulin ( HBIG) and nucleoside/nucleotide analogs ( NUC) is the current standard of care for controlling hepatitis B recurrence after orthotopic liver transplantation ( OLT). However, long-term HBIG administration is associated with several unresolved issues, including limited availability and extremely high cost, and thus several protocols for treatment with low-dose HBIG combined with NUC or HBIG-free regimens have been developed. This article reviews recent advances in post- OLT hepatitis B virus ( HBV) control and future methodological directions. New NUC such as entecavir, tenofovir or lamivudine plus adefovir dipivoxil combinations induce a very low frequency of viral resistance. The withdrawal of HBIG after several months of OLT under new NUC continuation also has permissible effects. Even after HBV reactivation, NUC can usually achieve viral control when viral markers are strictly followed up. Another approach is to induce self-producing anti- HBV antibodies via vaccination with a hepatitis B surface antigen vaccine. However, HBV vaccination is not sufficiently effective in patients to treat liver cirrhosis type B after OLT because immune tolerance to the virus has already continued for several decades. Trials of its safety and cost-effectiveness are required. This review advocates a safe and economical approach to controlling post- OLT HBV recurrence. [ABSTRACT FROM AUTHOR]

Background: Combination therapy of intravenous hepatitis B immunoglobulin (ivHBIG) and nucleos(t)ide (NA) analogues is the best post-liver transplantation (LT) prophylactic measure for hepatitis B virus (HBV). However, to reduce the long-term drawbacks of ivHBIG, we evaluated the efficacy of sequential entecavir (ETV) monotherapy. Methods: Twenty-nine candidates with HBV-related liver disease were prospectively enrolled. The patients were selected if the patient was suitable for one of the following inclusion criteria: (1) NA-naïve patients except for ETV, and (2) negative HB e antigen (HBeAg) and undetectable HBV DNA at the time of LT. Post-LT HBV prophylaxis consisted of 1-year combination therapy with ETV (0.5 mg daily) plus ivHBIG per 5 weeks, followed by ETV monotherapy. The primary endpoint was the 2-year recurrence rate of HB. The median follow-up period was 31 months. Results: At the time of transplantation, HBeAg was positive in 21 % and HBV DNA was detectable in 52 % of the study participants. No HBV recurrence was reported during the first year. During the second year, HBV recurrence was noted in one who suffered from HCC recurrence without viral mutation. Recurrence free survival rates were 96.6 and 96.4 % at 1- and 2-year post-transplant by intention-to-treat analysis. One patient died of fungal infection. Conclusion: Sequential ETV monotherapy after 1-year combination therapy might be safe in NA-naïve replicators as well as non-replicators. [ABSTRACT FROM AUTHOR]