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The combination of hepatitis B immunoglobulin and potent nucleos(t)ide analogs after liver transplantation is considered as the standard of care for prophylaxis against hepatitis B virus recurrence. However, the recommended doses, route of administration, and duration of HBIG administration remain unclear. Moreover, hepatitis B immunoglobulin-free prophylaxis with potent nucleos(t)ide analogs has shown promising disease outcomes in preventing hepatitis B virus recurrence. The current recommendations, produced by the Turkish Association for the Study of the Liver, Acute Liver Failure and Liver Transplantation Special Interest Group, suggest a reduced need for hepatitis B immunoglobulin administration with effective long-term suppression of hepatitis B virus replication using potent nucleos(t) ide analogs after liver transplantation.

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.Conclusions: 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.

China has the highest burden of hepatitis B virus (HBV) infection in the world. By 2017, the number of people infected with HBV in China had exceeded 70 million [1]. HBV reactivation often occurs i...

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.

Backgrounds/Aims This study intended to evaluate patient safety and efficiency of facility utilization following simplified ultra-rapid intravenous infusion of hepatitis B immunoglobulin (HBIG) in recipients of hepatitis B virus-associated adult liver transplantation (LT), who visited our outpatient clinic. Methods Our simplified ultra-rapid infusion protocol was to directly infuse 50 ml volume of 10,000 IU HBIG for 20-25 minutes on an ambulatory basis. The incidence of adverse side-effects and the efficiency of facility utilization were assessed retrospectively. Results A total of 1,513 patients received 12,472 sessions of HBIG infusion according to simplified ultra-rapid infusion method. Of these, 1,172 patients were converted from conventional ultra-rapid infusion method, and received 8,352 sessions of HBIG infusion for 18 months (mean 7.1 times; 4.8 times per year). The remaining 341 de novo patients received 4,120 sessions of HBIG infusion for 18 months (mean 12.1 times; 8.1 times per year). None of these patients experienced any adverse side-effects following the simplified ultra-rapid infusion. The maximal capacity of HBIG infusion sessions at the injection facility of our outpatient clinic was increased from 65-70 sessions to 80 sessions, after introduction of simplified ultra-rapid infusion method. Mean trough anti-HBs titer was lower, and mean interval of HBIG infusion was longer in the combination therapy group compared with HBIG monotherapy group. Conclusions Our high-volume study indicates that in nearly all LT recipients, rapid infusion of highly purified HBIG within 30 minutes was well-tolerated. This suggests that it would be reasonable to perform simplified ultra-rapid infusion protocol widely for patient convenience.

Background To evaluate the protective efficacy of a hepatitis B (HB) vaccination program in Taiwan among high-risk children. Material and methods Children born to HBeAg-positive mothers from 2001 to 2010 were invited back. Blood samples for hepatitis B virus (HBV) seromarkers were taken and the children underwent hepatobiliary ultrasonography. Perinatal factors including delivery mode and vaccination history were collected from their medical records. According to the results of HBV serological markers, the children were initially classified into five groups: HBV naive, HB vaccine responder, HBsAg carrier, recovered from HBV infection, and anti-HBc-positive alone. Children in the HBV naive and anti-HBc-positive alone groups who presented with an anamnestic response after a booster HB vaccine were re-assigned to the vaccine responder and recovered from infection groups, respectively. Results All of the 196 enrolled children received postnatal hepatitis B immunoglobulin (HBIG) and HB vaccinations, of whom one was HBV naive (0.5%), 109 were vaccine responders (55.6%), 21 were carriers (10.7%), and 65 recovered from infection (33.2%). Among the 21 carriers, 14 (66.7%) presented in the immunotolerant phase. Cesarean section was the only significant perinatal factor between the carriers (5.3%) and those who recovered from infection (37.7%) (p = 0.007). Conclusions In this study, there was a 43.9% HBV infection rate and 10.7% HBsAg carrier rate in high-risk Taiwanese children even after receiving HBIG and HB vaccinations. Cesarean section may protect newborns from becoming HBsAg carriers, while HBV genotype and time of HBIG injection did not contribute to the HBV carrier rate.

INTRODUCTION Hepatitis B virus infection has the highest rate of transmission out of the blood-borne viruses in health care workers. Exposure to HBsAg positive source should be managed based on Hepatitis B serology results. Given that Hepatitis B immunoglobulin (HBIG) is an expensive medication with limited stock levels, it should be given more attention to make sure of its optimum use. This trial aims to evaluate the effectiveness of a policy on the use of HBIG following needle stick and sharp injuries among health care workers. METHODS It is a quasi-experimental trial conducted at a Tertiary Care hospital in Saudi Arabia. The participants were health care workers who received HBIG following needle stick and sharp injuries from January 2018 to May 2020. Before and after implementing departmental guidelines and education on the post-exposure procedure, the trial re-evaluated the need for HBIG among the receivers. RESULTS A total of 60 health care workers received HBIG for needle stick and sharp injuries between the trial period (pre- and post-implementation). The percentage of patients who received inappropriate HBIG was significantly lower during the post-implementation of the guideline (30%) than that among the pre-implementation period (60%). Thus, the direct cost associated with the inappropriate use was reduced from SAR 30000 to SAR 13500 post-implementation. CONCLUSION The implementation of HBIG guidelines of use and education has led to a statistically significant decrease in its inappropriate use and led to cost reduction.

Amaç: Hepatit B’ye bağlı siroz nedeniyle karaciğer nakli yapılan hastalarda hepatit B nüksünün önlenmesi için kısa süreli düşük doz hepatit B immünoglobulini ile nükleotid analoğunun birlikte kullanımının etkinliğini belirlemek amaçlandı. Gereç ve Yöntem: 01 Aralık 2017 ile 01 Eylül 2018 tarihleri arasında İstanbul Aydın Üniversitesi Sağlık Uygulama ve Araştırma Hastanesi ve İstinye Üniversitesi Sağlık Uygulama ve Araştırma Hastanesi hastanelerinde Hepatit B’ye bağlı siroz veya hepatosellüler kanser nedeniyle karaciğer nakli yapılmış hastalar retrospektif olarak incelendi. Hastaların demografik bulguları, ameliyat öncesi viral belirteçleri, hepatosellüler kanser varlığı, HBV DNA varlığı, kullanılan hepatit B immünoglobulin dozu, ameliyat sonrası HBsAg, Anti-HBs, HBV DNA düzeyleri değerlendirildi. Bulgular: Ortalama yaşı 54±11 (aralık; 30-69) olan toplam 17 hasta (3 kadın, 14 erkek) çalışmaya dâhil edildi. Hastaların tümünün ameliyat öncesi HBsAg’si pozitif, 2 tanesinin ise HBV DNA’sı pozitifti. Ortalama takip süresi 16±3.3 ay (aralık; 12-22 ay) idi. Bu süreçte hiçbir hastada hepatit B nüksü gelişmedi. Sonuç: Bu çalışmada kısa süreli düşük doz hepatit B immünoglobulini ile nükleotid analoğu kombinasyonunun karaciğer nakli sonrası erken dönemde hepatit B nüksünü önlemede etkin olduğu görülmüştür. Bulgunun uzun dönem sonuçlarıyla desteklenmesi gerekmektedir. Aim: The aim of this study was to determine the efficacy of low dose hepatitis B immunoglobulin and nucleotide analog combination for prophylaxis to prevent recurrent hepatitis B infection after liver transplantation. Material and Methods: Patients with hepatitis B associated liver disease who underwent liver transplantation between 1 December 2017 and 1 September 2018 in Istanbul Aydın University Health Practice and Research Hospital and Istinye University Health Practice and Research Hospital retrospectively evaluated. Demographic data, preoperative viral markers, HBV DNA status, hepatocellular carcinoma status, dose of hepatitis B immunoglobulin, postoperative HBs Ag, Anti Hbs, HBV DNA levels were recorded. Results: Totally 17 patients (3 women, 14 men) with a mean age of 54±11 (range; 30-69) were evaluated. All of the recipients preoperative HBs Ag were positive and HBV DNA was positive in only two recipients. Mean follow-up was 16±3.3 (range; 12-22) months. There were no hepatitis B recurrence in this period. Conclusion: This study showed that combination of low dose hepatitis B immunoglobulin and nucleotide analog is an effective prophylaxis for recurrent hepatitis B infection for liver transplant recipients with HBVassociated liver disease. This conclusion should be supported with long term results.

Hepatitis B virus (HBV) infection is one of the main public health problems across the globe, since almost one third of the world population presents serological markers of contact with the virus. A profound impact on the epidemiology has been exerted by universal vaccination programmes in many countries, nevertheless the infection is still widespread also in its active form. In the areas of high endemicity (prevalence of hepatitis B surface antigen positivity > 7%), mother-to-child transmission represents the main modality of infection spread. That makes the correct management of HBV in pregnancy a matter of utmost importance. Furthermore, the infection in pregnancy needs to be carefully assessed and handled not only with respect to the risk of vertical transmission but also with respect to gravid women health. Each therapeutic or preventive choice deserves to be weighed upon attentively. On many aspects evidence is scarce or controversial. This review will highlight the latest insights into the paramount steps in managing HBV in pregnancy, with particular attention to recommendations from recent guidelines and data from up-do-date research syntheses.

With potent nucleos(t)ide analogue (NA) therapy, hepatitis B virus (HBV) is now an uncommon indication for liver transplant (LT) in North America. NA therapy, with or without hepatitis B immunoglobulin, results in low recurrence rates and excellent outcomes after LT. Direct-acting antiviral therapy for hepatitis C virus (HCV), results in cure in most patients, either before or after transplant. There are now descriptions of good clinical outcomes of transplant from HBV and HCV infected donors, as treatments are so effective and well tolerated. Hepatitis E virus in transplantation requires a high suspicion to diagnose and optimal therapy remains incompletely defined.

Chronic hepatitis B (CHB) is a major global health problem affecting an estimated 350 million people with more than 786000 individuals dying annually due to complications, such as cirrhosis, liver failure and hepatocellular carcinoma (HCC). Liver transplantation (LT) is considered gold standard for treatment of hepatitis B virus (HBV)-related liver failure and HCC. However, post-transplant viral reactivation can be detrimental to allograft function, leading to poor survival. Prophylaxis with high-dose hepatitis B immunoglobulin (HBIG) and anti-viral drugs have achieved remarkable progress in LT by suppressing viral replication and improving long-term survival. The combination of lamivudine (LAM) plus HBIG has been for many years the most widely used. However, life-long HBIG use is both cumbersome and costly, whereas long-term use of LAM results in resistant virus. Recently, in an effort to develop HBIG-free protocols, high potency nucleos(t)ide analogues, such as Entecavir or Tenofovir, have been tried either as monotherapy or in combination with low-dose HBIG with excellent results. Current focus is on novel antiviral targets, especially for covalently closed circular DNA (cccDNA), in an effort to eradicate HBV infection instead of viral suppression. However, there are several other molecular mechanisms through which HBV may reactivate and need equal attention. The purpose of this review is to address post-LT HBV reactivation, its risk factors, underlying molecular mechanisms, and recent advancements and future of anti-viral therapy.

Background Tenofovir disoproxil fumarate (TDF) administration in the third trimester for pregnant women with high HBV DNA load has been accepted as a wise practice to prevent mother-to-infant transmission (MTIT). However, for those women who missed the optimal time window of antiviral prophylaxis, this treatment is lacking in the current clinical guidelines. Methods Forty-eight pregnant women who did not receive antiviral prophylaxis before 28 weeks of gestation were screened and were administrated with TDF plus hepatitis B immunoglobulin (HBIG; TDF+HBIG group) or TDF alone (TDF group). HBV DNA inhibition and the safety profile were compared between two groups. Results A decline of HBV DNA load was observed in both groups after a short period of treatment, and no infant had MTIT. However, compared with the TDF group, the speed of HBV DNA load decline was more rapid ( P=0.002) and a much more striking HBV DNA load decline in the first 4 weeks of treatment was exhibited in the TDF+HBIG group ( P=0.001). The percentages of mothers with HBV DNA 10 IU/ml and 3 log10 IU/ml at delivery were both much higher in the TDF+HBIG group than the TDF group ( P=0.034 and 0.024, respectively). TDF and HBIG were found to be well-tolerated with no safety concerns in the mothers and their infants. Conclusions TDF plus HBIG treatment resulted in a rapid HBV DNA load decline in high-risk women who missed the optimal time window of antiviral prophylaxis in pregnancy, which potentially protected infants from HBV infection.

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 mu g 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. (C) 2017 Elsevier Ltd. All rights reserved.

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., Graphical Abstract

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.

Background: Hepatitis B infection is a potentially life-threatening liver infection. The burden is more in the less developed countries. Vaccination is the most cost-effective way to control hepatitis B virus (HBV) infection and its chronic complications globally. Active-passive immunoprophylaxis using hepatitis B immunoglobulin combined with recombinant hepatitis B vaccine is recommended for infants of women with chronic HBV infection. This study aimed to determine the effectiveness of the hepatitis B recombinant vaccine alone or combined with hepatitis B immunoglobulin.Methods: The study was a prospective longitudinal study. Patients were selected using a convenient sampling technique. The study spanned between 1 January 2017 and 31 December 2018. Data analysis was with SPSS version 21.Results: The unit recorded 1690 deliveries during the recruitment period, 70 eligible patients were recruited thus giving an incidence of 4.1%. 74.3% of the recruited patients were HBeAg negative while 25.7% were HBeAg positive. 52.9% of the babies had only recombinant HB recombinant vaccine while 47.1% had combined hepatitis B immunoglobulin and the recombinant vaccine at birth. The HBeAg status of mothers played a significant factor in the HBsAg positivity of babies two months after the completion of immunoprophylaxis against HBV.Conclusions: Giving recombinant HBV vaccine in combination with the HBV immunoglobulin is the standard practice, this may not always be so based on the findings from this study. However, the population studied is too small to make a categorical statement thus a larger population needs to be studied.

Liver transplant (LT) is now an established indication for patients with chronic hepatitis B, mainly because of the development and use of hepatitis B immunoglobulin (HBIG) and oral antivirals for prophylaxis. The combination of low-dose HBIG and antivirals has been considered the standard prophylaxis regimen to prevent post-LT recurrence of hepatitis B. The important remaining issues are related to the long-term cost of HBIG and the risk of escape hepatitis B virus (HBV) mutants. Strategies for prevention of HBV after LT are constantly improving. With the availability of new nucleoside/nucleotide analogues, new post-LT strategies also should emerge.

Background The aim of this study was to determine the long-term efficacy of nucleos(t)ide analog (NA) and low-dose hepatitis B immunoglobulin (HBIG) combination treatment for preventing post-transplant hepatitis B virus (HBV) recurrence. Methods A total of 296 patients with HBV-associated liver disease who underwent liver transplantation (LT) were enrolled. A combination of a daily NA and low-dose HBIG was used after LT. Results The median follow-up period was 46 months. HBV recurrence occurred in eight patients. The cumulative probability of HBV recurrence at 1, 3, 5, and 7 years was 1%, 3%, 3%, and 4%, respectively. Seven were on lamivudine (LMV) or adefovir dipivoxil (ADV), or LMV and ADV and HBIG combination treatment and one entecavir (ETV) and HBIG. With Cox regression analysis, HBV recurrence was determined to be associated with the presence of hepatocellular cancer (HCC) prior to LT (HR: 12.3, P=.02). Overall, 44 patients died. Survival was significantly better in the ETV or tenofovir disoproxil fumarate (TDF) and HBIG group than the other group (P

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., Graphical Abstract

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 6log10 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 3.4log10 copies/mL, P

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 naive 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.

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.

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.

Background: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.Objective: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.Results and Conclusion: :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.

Hepatitis B immune globulin (HBIG) has been an integral component of prophylaxis against hepatitis B virus (HBV) recurrence in liver transplantation (LT) recipients, but HBIG is costly and inconvenient to administer, prompting consideration of alternative regimens.In this retrospective cohort, we report on the success of antiviral therapy combined with a short course (in hospital only) HBIG in liver transplant recipients with HBV DNA less than 100 IU/mL pre-LT.A total of 42 hepatitis B surface antigen (HBsAg) positive, human immunodeficiency virus and hepatitis D virus-negative patients with pretransplant HBV DNA undetectable to 100 IU/mL who received HBIG 5000 IU in anhepatic phase and daily for 5 days together with nucleos(t)ide analogues indefinitely yielded 1- and 3-year cumulative incidences of recurrence, defined by positive serum HBsAg, of 2.9% (upper 95% confidence interval, 19%). One patient had HBV viremia 16 months post-LT without detectable HBsAg. Both patients with either HBsAg positivity or viremia had recurrent hepatocellular carcinoma diagnosed within a month of detection. Post-LT survival was 98% and 94% at 1 and 5 years, respectively.We conclude that a very short course of HBIG combined with long-term antiviral therapy is highly effective in preventing HBV recurrence and should be the preferred strategy for LT recipients with undetectable or low-level viremia at time of LT.

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.

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.

Life-long hepatitis B immunoglobulin (HBIG) administration is a main component of prophylactic strategy to prevent hepatitis B virus (HBV) reinfection after liver transplantation (LT). Long-term effects of HBIG treatment are known only for intravenous (IV) and intramuscular formulations. To evaluate safety and efficacy of self-administered SC HBIG, 135 LT patients receiving a 48-week treatment were analyzed. The dose of HBIG was 500 IU or 1000 IU if body weight was75 kg or ≥75 kg, respectively. Patients were switched from the monthly IV HBIG treatment to weekly SC HBIG 2-3 weeks after the last IV dosage. All patients were able to SC self-injection after a single training. The treatment was effective in maintaining trough anti-HBs levels100 IU/L. No severe drug-related side effects occurred. Fifteen injection-site small hematomas and four cases of mild itch occurred. At the end of the study, anti-HBs median titer was 232 IU/L (115-566 IU/L) and 97.8% of patients had an anti-HBs level150 IU/L. Due to high mean level of anti-HBs titers observed during this study, individualized treatment schedules should be further investigated. In conclusion, SC HBIG for long-term prophylaxis of post-LT HBV reinfection resulted safe, well accepted, and effective in maintaining adequate anti-HBs levels.

Background A combination of hepatitis B immunoglobulin and nucleos(t)ide analogues is the current standard of care for controlling hepatitis B recurrence after orthotopic liver transplantation (OLT). However, frequent immunoglobulin treatment is expensive and inconvenient. This study investigated the efficacy of hepatitis B virus (HBV) vaccination in preventing the recurrence of hepatitis B after living donor OLT. Methods Twenty-seven patients who had undergone living donor OLT participated in the study; five had acute HBV infected liver failure (ALF-OLT) and 22 had HBV related liver cirrhosis (LC-OLT). Hepatitis B surface antigen (HBsAg)-containing vaccine was administered to them for at least 1 year after transplantation and continued once monthly for up to 36 months post-OLT. Patients who had anti-HBs antibody titers above 100 mIU/mL for a minimum of 6 months without immunoglobulin administration were defined as good responders; the others were defined as poor responders. Interferon-γ enzyme-linked immunospot assays against HBs and HBc antigens were used to assay cellular immune responses. Results All five of the ALF-OLT patients had good responses after a median of four (range 2.5–5) vaccinations. Nine of the 22 LC-OLT patients had good responses after a median of 19 (range 11.5–30) vaccinations. Among the LC-OLT group, those with livers donated by relatively higher-aged, marital and high-titer anti-HBs antibody donors were good responders. LC-OLT patients classed as good responders showed interferon-γ responses comparable to those of the ALF-OLT patients. Conclusions The ALF-OLT and LC-OLT patients who received livers from relatively higher-aged, marital, high-titer anti-HBs antibody donors were the best candidates for HBV vaccine administration. Boosting donors before transplantation may facilitate later vaccine response of the recipients.

Introduction: Health Care Workers (HCWs) are at risk of occupational transmission of HIV, Hepatitis B and Hepatitis C, which can be minimized by following guidelines for standard precautions as well as taking Post Exposure Prophylaxis (PEP) measures. There are limited studies from India documenting details of PEP for HIV and Hepatitis B. Aim: We aimed to study the efficacy, tolerance, details of PEP regimens used among HCWs exposed to HIV and Hepatitis B as well as vaccination status and (Anti-Hepatitis B Surface Antigen) anti-HBS Antibody Titre Level Among HCWs exposed Hepatitis B. Study Design: This retrospective observational study was done at a rural based tertiary care teaching centre of Western India. Materials and Methods: Hospital Infection Control Committee of our institute was maintaining a record of all reported incidences of HIV and Hepatitis B positive exposures since 2003. We analysed reported incidences of exposures to HIV and Hepatitis B positive source occurred during the period of January 2003 to December 2015. Results: Of the total 96 exposures, 48 were to HIV and 48 were to Hepatitis B. Of the 48 exposures to HIV, PEP was warranted in 39. Of 39 exposures, only 14 (35.9%) received PEP within two hours. Basic regimen was used in 22 and expanded in 17 exposures. Only 12 (31.6%) reported side effects to PEP. Zidovudine based regimen was less well tolerated. All side effects were reported by female HCWs only. Of the 48 exposed to Hepatitis B, 33 (68.6%) were completely vaccinated. Out of 33, titre result was not available for eight. Three (12.0%) of remaining 25 were having low titre ( 100mIU/ml. Of the 48, in 17 (35.4%) incidences no action was required; 23 (47.9%) were managed with booster dose of Hepatitis B vaccine and eight (16.7%) with Hepatitis B immunoglobulin. No cases of sero-conversion was reported either for HIV or Hepatitis B from available data. Conclusion: Inspite of high incidences of exposures to HIV or Hepatitis B positive source, good efficacy of PEP was observed with no sero-conversion. PEP for HIV was well tolerated; female HCWs were less tolerant. Study emphasized the need for creating awareness about timely reporting of incidence, achieving maximum vaccination against Hepatitis B for all HCWs and need for anti-HBS antibody titre.

Hepatitis B immunoglobulin (HBIG), given in combination with nucleos(t)ide therapy, has reduced the rate of recurrent hepatitis B virus (HBV) following liver transplantation (LT), although the most effective protocol is unknown. We have retrospectively evaluated the use of long-term nucleos(t)ide analog in combination with one yr of low-dose HBIG. One hundred and fifty-two adults with HBV-related liver disease underwent LT in our center from January 1999 to August 2009; of these, 132 patients who received one yr of HBIG combined with long-term nucleos(t)ide analogs (largely on lamivudine [LAM] alone, n = 97) afterward were included for the purposes of this study. Median follow-up post-transplantation was 1752 d. Patient survival was 93.9%, 86.9% and 84.1% at 1, 5, and 10 yr, respectively; none of the 17 deceased patients had recurrent HBV. HBV recurrence was observed in nine patients (all received LAM+HBIG), yielding recurrence rates of 2.3%, 5.1%, and 8.6% at 1, 3, and 5/10 yr, respectively. All recurrences were successfully managed, usually with additional antiviral treatment. In conclusion, this study, with its long-term follow-up, demonstrates that short course of low-dose HBIG (without anti-HBs monitoring) combined with the use of long-term nucleos(t)ide analog is effective and less cumbersome than many protocols in current use.

Introduction. Hepatitis B virus (HBV) related liver transplant (LT) recipients face a high risk of HBV reinfection in the absence of continuous post-operative HBV prophylaxis. Combination HBV prophylaxis with hepa-titis B immune globulin (HBIg) and nucleos(t)ide anti-viral agents prevents HBV recurrence in 90 to 100% of patients who undergo transplantation for hepatitis B and is considered the standard of care in Canada. Post liver transplant HBV prophylaxis protocols vary with regard to the dosing, duration and routes of HBIg administration. All Canadian transplant centres managing liver transplant patients were surveyed as to their HBV transplant protocols. Results. Results of the survey showed that the majority of the Canadian transplant centres use an oral antiviral in combination with long term or indefinite HBIg for prevention of HBV recurrence post liver transplantation. Studies were done to test new protocols using lower HBIg doses given intramuscularly or subcutaneously alone or in combination with antiviral agents. Conclusion. Long term HBIg administration post transplantation in combination with antiviral agents is an integral part of Canadian HBV related liver transplant protocol.

A combination of hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogues (NUCs) is currently recommended as prophylaxis against the recurrence of hepatitis B virus (HBV) after liver transplantation (LT), but the optimal protocol is a matter of controversy. The aim of this study was the identification of factors associated with post-LT HBV recurrence in patients receiving HBIG and NUCs. We searched MEDLINE and PubMed for studies in English about the effectiveness of HBIG and NUCs [lamivudine (LAM) and/or adefovir dipivoxil (ADV)] against post-LT HBV recurrence (January 1998 to June 2010). Forty-six studies, which included 2162 HBV LT recipients, met the selection criteria. Patients receiving HBIG and LAM experienced HBV recurrence more frequently than patients receiving HBIG and ADV with or without LAM [6.1% (115/1889) versus 2.0% (3/152), P = 0.024], although they also were more frequently treated with indefinite HBIG prophylaxis (90% versus 57%, P < 0.001). For patients receiving HBIG and LAM, a lower frequency of HBV recurrence was associated with a high HBIG dosage (≥10,000 IU/day) versus a low HBIG dosage (

Objectives: This study was conducted to determine the effectiveness of a multicomponent intervention in Sanliurfa Gynecology and Obstetrics Hospital (SGOH), which is designed to overcome the obstacles encountered in the application of HBsAg testing to all delivering women, the administration of hepatitis B vaccine and Hepatitis B Immunglobulin(HBIG) to newborns of HBsAg positive pregnant women. Methods: This is an intervention study, conducted between December 15, 2007 and December 30, 2008. Intervention procedure is composed of four methods; namely, motivation of all parties through academic leadership, implementation of workshops to determine the obstacles, provision of administrative commitment, and training of healthcare personnel. Results: In 2007, a total of 18,709 deliveries were realized in SGOH; HBsAg testing was performed in only 16.5% of the pregnant women and 0.8% of these women were found to be HBsAg positive. It was determined that HBIG was administered to 28.2% of newborns of HBsAg positive mothers and hepatitis B vaccine was given to 71.4% (n=13349) of all newborns. After the intervention, the increase in HBsAg test application status, HBsAg positivity, HIBG administration and hepatitis B vaccination was 6.0, 5.8, 2.0 and 1.2 fold, respectively (P

A considerable proportion of liver transplantation recipients who receive hepatitis B immunoglobulin (HBIG) monotherapy for hepatitis B virus (HBV) prophylaxis develop resistance to HBIG. We retrospectively assessed the efficacy of HBV prophylaxis in 1524 patients who received primary high-dose HBIG monotherapy (n = 1463) or with a preemptive antiviral add-on as secondary combination therapy (n = 61). At a median follow-up time of 57 months, 106 (7.3%) patients receiving HBIG monotherapy experienced HBV recurrence, with a 10-year HBV recurrence rate of 9.8%, compared to none of the patients receiving preemptive combination therapy (P = 0.047). Thirteen patients (12.3%) with HBV recurrence failed antiviral therapy, leading to death or retransplantation. Response rates to rescue therapy before and after use of adefovir/entecavir were 44.4% and 91.8%, respectively. Acute exacerbation was not associated with treatment failure, but required prolonged treatment. Of 84 surviving patients with HBV recurrence, 44 (52.4%) showed no evidence of blood HBV DNA. The Gly145Arg mutation was found in 11 of 15 (73.3%) patients, whereas 25 of 71 (35.2%), 2 of 29 (6.9%), and 4 of 8 (50%) patients were resistant to lamivudine, adefovir, and entecavir, respectively. In conclusion, our finding of a 10-year HBV recurrence rate of 9.8% in patients receiving high-dose HBIG monotherapy indicates that this treatment is effective but requires complementary measures. Strict surveillance following HBIG monotherapy is necessary to enhance responses to rescue antiviral therapy. Preemptive conversion to combination therapy has a complementary role in prophylaxis with primary high-dose HBIG monotherapy, especially for patients at high risk of HBV recurrence.

Summary Hepatitis B re-infection prophylaxis is crucial for graft and recipient survival for transplanted patients and is administered routinely after liver transplantation for hepatitis B. Aim of the current study was the investigation of efficacy, safety and feasibility of home-treatment of a novel human hepatitis B immunoglobulin BT088 (Zutectra®) after weekly subcutaneous application in liver-transplanted patients. A total of 23 patients (5 female, 18 male, median age 51 years) were enrolled and switched from monthly IV to weekly SC hepatitis B immunoglobulin administration. During a period of 18 weeks (optional 24 weeks) anti-HBs levels, signs of re-infection, adverse events and feasibility of self-administration were studied. After 8 weeks of training patients showing good compliance and stable antibody titres were allowed to start self-administration at home. All patients maintained a safety level of >100 U/l anti-HBs. No failure was noted, no re-infection occurred. A total of 10 treatment-emergent events were assessed as related to study drug application (injection-site haematoma, headache, abdominal pain, fatigue and haematuria). High numbers of self-administration (287 vs. 122 by staff) demonstrated general feasibility of SC administration. Weekly subcutaneous administration of BT088 (Zutectra®– registered trade mark in the EU) is effective, safe and presents an easy-to-apply treatment option for combined hepatitis B virus re-infection prophylaxis in liver transplant patients (Eudra CT Number: 2005-003737-40).

Key Points 1. Transplantation for HBV-related HCC is increasing in the West, whilst HBV-relate liver failure is decreasing. 2. Combination lamivudine plus HBIG reduces the risk of HBV recurrence to less than 5%. 3. Low-dose IM HBIG ihas similar efficacy and better cost effectiveness than high-dose IV HBIG when combined with oral nucleos(t)ide therapy. 4. HBIG may be discontinued in low risk recipients (undetectable HBV DNA prior to transplant). 5. Combination of new potent antivirals without cross resistance may minimise the future need for post-operative HBIG. Liver Transpl 16:S36-S39, 2010. © 2010 AASLD.