Explore the vast range of titles available.

Background and aims This study aimed to compare the efficacy of shorter vs. longer tenofovir disoproxil fumarate (TDF) prophylaxis in preventing hepatitis B virus (HBV) relapse in cancer patients with chronic hepatitis B (CHB) undergoing chemotherapy. Methods This phase IV, prospective randomized trial enrolled cancer patients with CHB from 2014 to 2019 in Taiwan. Included patients were randomized to receive either 24- (Arm A) or 48-week (Arm B) post-chemotherapy TDF and compared for cumulative incidence of virological and clinical relapse. Logistic regressions were conducted to determine the factors associated with HBV relapse. Results One hundred patients were randomized, and 41 patients in Arm A and 46 in Arm B completed the TDF treatment. No significant difference was found in cumulative incidence of virological relapse (Arm A: 94.4%, Arm B: 93.1%, p  = 0.110) or clinical relapse among patients with baseline HBV DNA > 2000 IU/mL (Arm A: 38.9%, Arm B: 26.7%, p  = 0.420) between the two arms. High baseline HBV DNA ≥ 10,000 IU/mL (OR = 51.22) and HBsAg ≥ 1000 IU/mL (OR = 8.64) were independently associated with an increased virological relapse. Alanine aminotransferase (ALT), serum phosphorus, vitamin D, and estimated glomerular filtration rate (eGFR) remained stable throughout the study. Conclusions The 24-week preventative TDF has comparable efficacy to the 48-week treatment in virologic and clinical relapse. High baseline HBsAg or HBV DNA is associated with a higher risk of HBV relapse. These findings imply a 24-week duration of TDF treatment with a close monitor for patients with a high baseline viral load. Lay summary Hepatitis B virus infection is a prominent cause of liver cancer and chronic liver disease and affected millions of people worldwide. When HBV-infected people are exposed to immunosuppressive medication or chemotherapy for cancer, the chance of HBV reactivation rises considerably. This trial showed 24-week tenofovir disoproxil fumarate (TDF) may be sufficient for preventing HBV relapse in cancer patients receiving chemotherapy. Clinical Trial registration number NCT02081469.

Hepatitis B virus (HBV) infection is a major public health problem, with an estimated 296 million people chronically infected and 820 000 deaths worldwide in 2019. Diagnosis of HBV infection requires serological testing for HBsAg and for acute infection additional testing for IgM hepatitis B core antibody (IgM anti-HBc, for the window period when neither HBsAg nor anti-HBs is detected). Assessment of HBV replication status to guide treatment decisions involves testing for HBV DNA, whereas assessment of liver disease activity and staging is mainly based on aminotransferases, platelet count, and elastography. Universal infant immunisation, including birth dose vaccination is the most effective means to prevent chronic HBV infection. Two vaccines with improved immunogenicity have recently been approved for adults in the USA and EU, with availability expected to expand. Current therapies, pegylated interferon, and nucleos(t)ide analogues can prevent development of cirrhosis and hepatocellular carcinoma, but do not eradicate the virus and rarely clear HBsAg. Treatment is recommended for patients with cirrhosis or with high HBV DNA levels and active or advanced liver disease. New antiviral and immunomodulatory therapies aiming to achieve functional cure (ie, clearance of HBsAg) are in clinical development. Improved vaccination coverage, increased screening, diagnosis and linkage to care, development of curative therapies, and removal of stigma are important in achieving WHO's goal of eliminating HBV infection by 2030.

Chronic hepatitis B virus (HBV) infection affects about 296 million people worldwide and is the leading aetiology of cirrhosis and liver cancer globally. Major medical complications also include acute flares and extrahepatic manifestations. In addition, people living with HBV infection also experience stigma. HBV-related cirrhosis resulted in an estimated 331,000 deaths in 2019, and it is estimated that the number of deaths from HBV-related liver cancer in 2019 was 192,000, an increase from 156,000 in 2010. Meanwhile, HBV remains severely underdiagnosed and effective measures that can prevent infection and disease progression are underutilized. Birth dose coverage for HBV vaccines remains low, particularly in low-income countries or regions where HBV burden is high. Patients with HBV infection are inadequately evaluated and linked to care and are undertreated worldwide, even in high-income countries or regions. Despite the goal of the World Health Organization to eliminate viral hepatitis as a public health problem by 2030, the annual global deaths from HBV are projected to increase by 39% from 2015 to 2030 if the status quo remains. In this Review, we discuss the current status and future projections of the global burden of HBV infection. We also discuss gaps in the current care cascade and propose future directions.This Review provides an overview of the global epidemiology and burden of hepatitis B virus (HBV) infection, identifying gaps in the HBV care cascade and proposing some solutions to help reach the goal of WHO to eliminate HBV as a public health threat by 2030.

PreHevbrio® is a 3-antigen HBV vaccine (3-A-HBV) engineered to express the three HBV envelope proteins; the small ‘S' hepatitis B surface antigen (SHBs or HBsAg), the middle pre-S2 + HBsAg (MHBs) and the large PreS1 + PreS2 + HBsAg (LHBs) antigens. 3-A-HBV has been shown to induce superior and more durable antibody responses relative to a 1-A-HBV despite containing half the ‘S' antigen dose. To explain the mechanism(s) behind the high immunogenicity, the potential influence of mammalian glycosylation, HBs antigen conformation, anti-HBs epitope binding profiles and T-cell responses to the PreS antigens were investigated. In this paper, we demonstrate that glycosylation status does not play a role in the increased immunogenicity of the 3-A-HBV, but that the 3-A-HBV particles are able to induce T cell responses to PreS1 and PreS2 antigens. Epitope mapping demonstrated that the 3-A-HBV particles are inherently more antigenic than 1-A-HBV particles, leading to quantitative differences in the anti-HBs antibody response. Further, we demonstrate that the T cell responses significantly correlate with the higher observed anti-HBs titers and may contribute to the higher and more durable anti-HBs titers. This trial is registered at Clinicaltrials.gov (NCT03393754) and EudraCT (2017–001819-36). •PreHevbrio is a 3-antigen HBV vaccine shown to induce high anti-HBs titers following vaccination.•Immunological aspects of 3-A-HBV were studied to reveal the mechanisms behind the immunogenicity.•Epitope mapping revealed that 3-A-HBV particles are more antigenic than 1-A-HBV particles.•T cell responses may contribute to the higher and more durable anti-HBs titers.

People infected with human immunodeficiency virus (HIV) are more likely to be infected with hepatitis B virus (HBV), which is a significant public health concern. It is essential to provide protection through the hepatitis B vaccine and to stimulate higher and more sustained levels of anti-HBs antibodies to ensure long-term immunity. We aimed to enhance the duration of immunogenicity by implementing high-dose and multiple-schedule hepatitis B vaccination in adults infected with HIV. This open-label, parallel-group, randomised controlled trial (RCT) was conducted between May 2020 and January 2021 at the Second Hospital of Yuncheng. Patients were randomised to receive 3 or 4 doses of 20 μg or 60 μg of hepatitis B vaccine. The follow-up period was extended to 2022 to evaluate the duration of immunogenicity. The geometric mean concentration (GMC) and response rates of hepatitis B surface antibody (anti-HBs) at month 18 were 200.40 mIU/ml and 66.67 % (58/87) in the IM20 × 3 group, 382.20 mIU/ml and 75.58 % (65/86) in the IM20 × 4 group, 628.50 mIU/ml and 83.13 % (69/83) in the IM60 × 4 group, which were significantly different between the IM20 × 3 and IM60 × 4 groups (P < 0.017). In multivariate analysis, gender and vaccination regimens affected the duration of immunogenicity at month 18. Regarding the multiplicative scale, the interaction effect was significant between the male and the IM60 × 4 group after adjusting for confounders. In the one-year follow-up (month 18) of adults infected with HIV, four triple doses regimen of hepatitis B vaccine improved the duration of immunogenicity in male patients. •The four-triple-dose hepatitis B vaccination regimens boost the one-year duration of immunogenicity.•Gender and vaccination regimens had an effect on the duration of immunogenicity.•The interaction effect was significant between male and the IM60 × 4 group after adjusting for confounders.

Neonatal hepatitis B vaccination has been implemented worldwide to prevent hepatitis B virus (HBV) infections. Its long-term protective efficacy on primary liver cancer (PLC) and other liver diseases has not been fully examined. The Qidong Hepatitis B Intervention Study, a population-based, cluster randomized, controlled trial between 1985 and 1990 in Qidong, China, included 39,292 newborns who were randomly assigned to the vaccination group in which 38,366 participants completed the HBV vaccination series and 34,441 newborns who were randomly assigned to the control group in which the participants received neither a vaccine nor a placebo. However, 23,368 (67.8%) participants in the control group received catch-up vaccination at age 10-14 years. By December 2013, a total of 3,895 (10.2%) in the vaccination group and 3,898 (11.3%) in the control group were lost to follow-up. Information on PLC incidence and liver disease mortality were collected through linkage of all remaining cohort members to a well-established population-based tumor registry until December 31, 2013. Two cross-sectional surveys on HBV surface antigen (HBsAg) seroprevalence were conducted in 1996-2000 and 2008-2012. The participation rates of the two surveys were 57.5% (21,770) and 50.7% (17,204) in the vaccination group and 36.3% (12,184) and 58.6% (17,395) in the control group, respectively. Using intention-to-treat analysis, we found that the incidence rate of PLC and the mortality rates of severe end-stage liver diseases and infant fulminant hepatitis were significantly lower in the vaccination group than the control group with efficacies of 84% (95% CI 23%-97%), 70% (95% CI 15%-89%), and 69% (95% CI 34%-85%), respectively. The estimated efficacy of catch-up vaccination on HBsAg seroprevalence in early adulthood was 21% (95% CI 10%-30%), substantially weaker than that of the neonatal vaccination (72%, 95% CI 68%-75%). Receiving a booster at age 10-14 years decreased HBsAg seroprevalence if participants were born to HBsAg-positive mothers (hazard ratio [HR]  = 0.68, 95% CI 0.47-0.97). Limitations to consider in interpreting the study results include the small number of individuals with PLC, participants lost to follow-up, and the large proportion of participants who did not provide serum samples at follow-up. Neonatal HBV vaccination was found to significantly decrease HBsAg seroprevalence in childhood through young adulthood and subsequently reduce the risk of PLC and other liver diseases in young adults in rural China. The findings underscore the importance of neonatal HBV vaccination. Our results also suggest that an adolescence booster should be considered in individuals born to HBsAg-positive mothers and who have completed the HBV neonatal vaccination series. Please see later in the article for the Editors' Summary.

•Phase 3 trial of investigational hepatitis B vaccine in adults 40–70years old.•2 doses of HBsAg-1018 demonstrated superior seroprotection to 3 doses of HBsAg-Eng.•HBsAg-1018 induced earlier seroprotection than HBsAg-Eng.•The safety profile of HBsAg-1018 was similar to that of HBsAg-Eng. The currently licensed hepatitis B vaccines have limitations including hyporesponsiveness in older adults, poor compliance, and the extended time for most persons to develop seroprotection (e.g. >6months). A vaccine containing HBsAg combined with a Toll-like receptor 9 agonist adjuvant (HBsAg-1018) has been developed to overcome these limitations. A Phase 3, multicenter, randomized, subject- and observer-blinded, active-controlled trial was conducted among healthy subjects 40–70years of age comparing the immunogenicity and safety of two doses of HBsAg-1018 at 0 and 4weeks to three doses of licensed hepatitis B vaccine, HBsAg-Eng, at 0, 4, and 24weeks. The primary immunogenicity endpoint was noninferiority of the seroprotection rate (SPR; % with anti-HBs≥10mIU/mL) of HBsAg-1018 compared to the SPR of HBsAg-Eng at 8 weeks following the last dose of vaccine. Conditional upon meeting noninferiority, superiority of HBsAg-1018 over HBsAg-Eng was assessed. Safety was compared between the two vaccines. At the primary endpoint, the SPR for the HBsAg-1018 group (90.0%) was superior to the SPR for the HBsAg-Eng group (70.5%) with an SPR difference of 19.5% (95% CI, 14.7%, 24.7%). At week 28 when the SPR peaked in the HBsAg-Eng group (72.8%), the SPR in the HBsAg-1018 group (94.8%) was significantly higher than in the HBsAg-Eng group. The SPR in the HBsAg-1018 group was significantly higher than in the HBsAg-Eng group at each study visit from week 4 through week 52. The safety profiles for the two vaccines were similar. When compared to the HBsAg-Eng three-dose regimen given at 0, 1, and 6months, HBsAg-1018 demonstrated superior seroprotection with only two doses at 0 and 1month. The safety profile of HBsAg-1018 was comparable to that of the licensed vaccine, HBsAg-Eng. HBsAg-1018 would provide a significant public health contribution toward the prevention of hepatitis B infection.

► Two doses of an HBV-ISS demonstrated superior immunogenicity to three doses of HBV-Eng measured at week 28. ► HBV-ISS had a safety profile that was similar to the currently licensed HBV-Eng although injection-site reactions were more common. ► HBV-ISS achieved higher levels of protection after the first and second doses. The currently licensed aluminum-hydroxide-adjuvanted hepatitis B vaccines require three doses over a 6-month period to achieve high rates of protection in adults. We compared tolerability and immunogenicity of two doses of an investigational hepatitis B vaccine using hepatitis B surface antigen adjuvanted with an immunostimulatory phosphorothioate oligodeoxyribonucleotide (HBV-ISS) to three doses of a licensed alum-adjuvanted vaccine (HBV-Eng). In this randomized, observer-blind study, healthy adults received two doses of HBV-ISS at 0 and 4 weeks or three doses of HBV-Eng at 0, 4, and 24 weeks. The primary immunogenicity endpoint was the seroprotection rate (antibody≥10mIU/mL) 8 weeks after the second dose of HBV-ISS compared to 4 weeks after the third dose of HBV-Eng. A total of 2415 participants were randomized in a ratio of 3:1 to HBV-ISS (n=1809) and HBV-Eng (n=606). The percentage of subjects exhibiting a seroprotective immune response at the primary time point was significantly higher (95.1%) for HBV-ISS than for HBV-Eng (81.1%). Superiority of the seroprotective rates for HBV-ISS was demonstrated at all time points measured. Geometric mean concentrations were also significantly higher in the HBV-ISS group at all time points measured except at week 28 (24 weeks post-second dose of HBV-ISS and 4 weeks post-third dose HBV-ISS) at which time the antibody concentrations were similar. Both vaccines were welltolerated although injection-site reactions were reported at a higher rate in HBV-ISS recipients. A short, two-dose regimen of HBV-ISS induced a superior antibody response than a three-dose regimen of a licensed hepatitis B vaccine and was well tolerated.

Hepatitis B (HBV) prevalence remains high in Sub Saharan Africa and among some key populations such as those with continued exposure through sexual contact. We assessed the HBV status among potential participants who were screened for simulated HIV vaccine efficacy trials in Kenya and Uganda. We conducted a cross sectional analysis of data collected from individuals who were screened in Kenya (Nairobi) and Uganda (Entebbe and Kampala). The studies followed hypothetical procedures of an HIV vaccine efficacy trial and aimed to enroll HIV negative key and vulnerable populations at elevated risk of HIV acquisition. HBV status was the main outcome categorized using Hepatitis B surface antigen (HBsAg) and total Hepatitis B core antibody (HBcAb). Baseline characteristics potentially associated with never being infected were analyzed using logistic regression. We screened 1,366 participants with mean age (SD) 28.7 (7.3) years. Overall, 46.6% were from Entebbe, 50.7% had secondary or higher level of education, 76.4% had informal high-risk jobs and 56.3% were male. Kampala had only female participants contributing 60.6% of females screened. Of the screened participants, 94.7% and 3.4% were negative and positive for HBsAg respectively. The prevalence on HBV infection was 3.9% among males and 2.8% among females while prevalence by site was: Entebbe (4.9%); Kampala (4.1%) and Nairobi (0.3%). The highest HBV prevalence was found among participants aged 25-29-years (5.2%), those with primary level education (4.5%), and those in informal low risk jobs (6.5%). Considering 1265 participants with complete data on HBsAg and HBcAb-Total, HBV status was never infected (67.9%), past infection (28.5%), chronic infection (3.2%) and acute infection (0.5%). Of 859 who were never infected, 685 (79.7%) were tested for anti-HBs titers of whom 60 (8.8%) had titers >10IU/L (immune due to vaccination). The odds of never being HBV infected were lower among older individuals 25-29 years (AOR 0.51; 95%CI 0.36-0.71) and ≥30 years (AOR 0.35; 95% CI 0.25-0.49). The odds were higher among participants with informal high-risk jobs from Kampala (AOR 2.21; 95% CI 1.41-3.47) and Nairobi (AOR 2.61; 95% CI 1.72-4.00) compared to those from Entebbe. HBV prevalence and immunity due to vaccination were low among HIV negative individuals who are eligible for HIV vaccine trials and prevalence varies by age, education level and main occupation. Younger individuals and those recruited from existing cohorts/ clinics have a higher likelihood of having no prior HBV infection. HIV prevention intervention trials are a platform to identify individuals that need HBV vaccination.

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. 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. 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). 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.