Optimization of Mother-to-Child Hepatitis B Virus Prevention Program: Integration of Maternal Screening and Infant Post-vaccination Serologic Testing.

BACKGROUND: Evaluation of the impact on mother-to-child transmission (MTCT) of a HBV-prevention program that incorporates maternal antiviral prophylaxis is hindered by the limited availability of real-world data. METHODS: This study analyzed data on maternal HBV screening, neonatal immunization, and post-vaccination serologic testing (PVST) for HBsAg among at-risk infants born to HBV carrier mothers from the National Immunization Information System during 01/01/2008-31/12/2022. Through linkage with the National Health Insurance Database, information of maternal antiviral therapy was obtained. Multivariate logistic regression was performed to explore MTCT risk in relation to infant-mother characteristics and prevention strategies. RESULTS: Totally, 2,460,218 deliveries with maternal HBV status were screened. Between 2008 and 2022, the annual HBsAg and HBeAg seropositivity rates among native pregnant women aged 15-49 years decreased from 12.2% to 2.6% and from 2.7% to 0.4%, respectively (p for both trends < 0.0001). Among the 22,859 at-risk infants undergoing PVST, the MTCT rates differed between infants born to HBsAg-positive/HBeAg-negative and HBeAg-positive mothers (0.75% and 6.33%, respectively; p < 0.001). The MTCT rate was 1.72% (11/641) for infants born to HBeAg-positive mothers with antiviral prophylaxis. MTCT risk increased with maternal HBeAg-positivity (OR 9.29, 6.79-12.73) and decreased with maternal antiviral prophylaxis (OR 0.28, 0.16-0.49). For infants with maternal HBeAg-positivity, MTCT risk was associated with mothers born in the immunization era (OR 1.40, 1.17-1.67). CONCLUSIONS: MTCT was related to maternal HBeAg-positivity and effectively prevented by maternal prophylaxis in the immunized population. At-risk infants born to maternal vaccinated cohorts might possibly pose further risk.

The high prevalence of occult hepatitis B infections among the partners of chronically infected HBV blood donors emphasizes the potential residual risk to blood safety.

A small percentage of couples who regularly donated blood in China tested positive for HBsAg. Although it is well known that blood donors can acquire hepatitis B virus (HBV) infection from a chronically infected sexual partner, the prevalence of occult hepatitis B infections (OBIs) among blood donations from partners of HBV-infected chronically infected spouses and the risk to blood safety remain poorly understood. Among 212 763 blood donors, 54 pairs of couples (108 donations) were enrolled because one partner tested positive for HBsAg. Several molecular and serological examinations were conducted. The origin of HBV transmission between sexual partners was investigated further. Also evaluated was the potential risk of HBV infection with OBIs. We identified 10 (10/54, 18.6%) sexual partners of chronically infected HBV donors who were positive for HBV DNA, including five samples (9.3%) with OBIs, of which 3 (3/54, 5.6%, 1 in 70 921 donations) passed the routine blood screening tests. Seven of the 10 HBV-DNA-positive couples contracted the virus possibly through sexual or close contact. Among infected couples, immune escape mutations were observed. A high prevalence of OBIs was found among the partners of chronically infected HBV blood donors, posing a potential threat to blood safety.

Comparative analysis of hepatitis B virus infections in blood donors born before and after the implementation of universal HBV vaccination in southern China.

BACKGROUND: In China, the vaccinated blood donors have rapidly increased by recent years, which may impact blood safety. The true prevalence of HBV between vaccinated blood donors and non-vaccinated blood donors should be explored. STUDY DESIGN AND METHODS: The samples of blood donors were collected and detected for serologic markers of HBV in the Shenzhen Blood Centre (SZBC). The discrepant results were tested with commercial electrochemiluminescence immunoassay (ELCI) for HBsAg, anti-HBs, HBeAg, Anti-HBe and Anti-HBc, alternative MPX ID NAT, nested PCR, and a quantitative real-time polymerase chain reaction (qPCR) assay for HBV DNA. The serological and molecular characteristics of HBV infected blood donors were analysed, and the effects on blood safety for donors born before and after the implementation of universal HBV vaccination were compared. RESULTS: Out of 242 presumed HBV infected donors from 26 318 donations, 131 (0.49%, [95% CI, 0.43-0.59]) chronic HBV infections (CHB, HBsAg detected with or without DNA), 58 (0.22%, [95% CI, 0.17-0.28]) occult hepatitis B infections (OBI, HBsAg not detected, assume anti-HBc positive and/or anti-HBs with HBV DNA) and 3 (0.011%, [95% CI, 0.0023-0.033]) window period (WP) infections were confirmed respectively. There were 28 CHBs (0.44%), 7 OBIs (0.11%) and 1 WP (0.016%) from vaccinated blood donor and 103 CHBs (0.52%), 51 OBIs (0.26%) and 2 WPs (0.01%) from non-vaccinated blood donor. The HBV+ (CHBs, OBIs and WPs) rate (0.56%) in vaccinated donors was lower than in non-vaccinated donors (0.78%, p < 0.05). The HBsAg titers of vaccinated infected blood donors (Median: 128.8 IU/ml) were much higher than non-vaccinated infected blood donors (58.4 IU/ml). The OBI yield rates in the vaccinated blood donors was significantly lower than the non-vaccinated blood donors (p < 0.05). There 102/124 (82.3%) samples were genotype B, 22/124 (17.7%) were genotype C respectively. There was no significant difference in the distribution of genotype between non-vaccinated blood donors (B/C, 86/17) and vaccinated blood donors (B/C, 23/6; p > 0.05). High frequency of vaccine escape mutations M133L (32.4%) and E164G in S region of genotype B strains and substitution L175S (40.9%) related to vaccine escape in S region of genotype C strains were identified. CONCLUSION: The universal HBV vaccination program markedly reduces the risk of HBV infection in blood donors, and provides a significant guarantee for the safety of blood transfusion. Several important mutations detected related vaccine escape and notable mutations needed further investigated.

Is it possible to halve the incidence of liver cancer in China by 2050?

A substantial proportion of liver cancers is attributable to chronic infection with hepatitis B and C (HBV/HCV). Liver cancer could become the second cancer, after cervical, to be effectively controlled globally, if proven interventions such as vaccination can be implemented on a large scale. In 2018, the global mortality rate for liver cancer was estimated to be 8.5 per 100 000 individuals. Given patterns of HBV infection and immigration across countries, liver cancer control requires combined, global action. Liver cancer trends vary between countries, in some Western countries, the incidence rates were relatively low but have increased in recent decades; conversely, in several Asian countries, the incidence rates have decreased over time. China has in the past contributed more than half of the global burden of liver cancer but more recently a national decline in liver cancer incidence has been observed. Here, we review the liver cancer burden and exposure to risk factors in China, compared to other countries. We also review the implementation status for primary and secondary prevention interventions and major outcomes achieved over the past three decades. Using Bayesian age-period-cohort analysis, we examine recent trends and based on these, predict that by 2050, the incidence of liver cancer in China could fall by half. We additionally survey the literature to identify current research needs, and review relevant national policies on liver cancer control in China. A comprehensive set of interventions is proposed to progress toward the long-term goal of liver cancer elimination based on the natural history and evidence-based interventions.

Effectiveness of hepatitis B vaccination in chronic HCV patients after successful generic direct acting antiviral therapy: significance of isolated hepatitis B core antibodies.

OBJECTIVE: Previous reports show conflicting results regarding hepatitis B virus (HBV) vaccine efficacy in Hepatitis C virus (HCV) infected individuals and in those with isolated hepatitis B core antibodies (HBcAb). We aimed to evaluate the effectiveness of HBV vaccine and identify possible factors that may contribute to hyporesponsivness in HCV-treated patients, including those with isolated HBcAb. METHODS: We conducted a prospective study with 118 enrolled chronic HCV patients who followed a 12-week regimen of direct acting antivirals (DAAs) and were evaluated for HBV serological markers. Eventually, 98 received appropriate HBV vaccination and were assessed for response. RESULTS: A total of 57.1% were vaccine responders although only 5.1% achieved a seroprotective level of HBsAb titre. The response rate was significantly lower among treated HCV patients with isolated HBcAb [2 (5.6%) vs. 40 (64.5%) respectively]. On multivariate analysis, advanced age [OR (95% CI) = 1.09 (1.02-1.17)] and presence of isolated HbcAb [OR (95% CI) = 39.59 (7.98-196.63)] were predictors of vaccine non-response. In our cost-effectiveness models, the cost of HBV serological screening was less than the nationally adopted non-screening approach. A model ratifying reinforced vaccination in non-responder HBcAb seropositive HCV patients would incur extra cost. CONCLUSION: Hyporesponsiveness to the HBV vaccination is frequent in chronic HCV patients even after achieving SVR following DAAs. Although there is no consensus on the clinical management of patients with isolated HBcAb, our cost-effectiveness options may support decision-making for better clinical benefit and proper health investments.

The impact of universal hepatitis B vaccine on the trend of liver cancer from the Global Burden of Disease Study 2017.

AIMS: This study aims to assess the trend of hepatitis B virus (HBV)-attributable liver cancer as well as the impact of HBV vaccine on it. METHODS: We retrieved data from Global Burden Disease study to estimate trends of HBV-attributable liver cancer by region and age from 1990 to 2017 and HBV vaccine data from World Health Organization to assess its impact on these trends for children (0-14 years), adolescents and young adults (15-29 years). Change of cancer cases, age-standardized incidence rate (ASR) and estimated annual percentage change (EAPC) were used to quantify the trends of HBV-attributable liver cancer. RESULTS: In this study, reduction in HBV-attributable cancer incident cases was found among children (from 2080 to 1430), adolescents and young adults (from 10 890 to 9090). In terms of ASR, overall reduction was observed globally by an average of -0.45% (95% CI: -0.62 to -0.29) per year in the same period. The highest reduction in ASR was found in adolescents and young adults with EAPC of -3.02 (95% CI: -3.57 to -2.46). Although the ASR has decreased from all the five regions with universal HBV immunization programme, it has increased in the region without universal vaccination and the highest increase was found among children with EAPC of 1.97 (95% CI: 1.71-2.23). CONCLUSION: Significant reduction in HBV-attributable liver cancer among children was mainly because of the universal HBV vaccination. However, the increasing trend of HBV-attributable liver cancer in region without universal HBV vaccination suggested the necessity of introducing universal immunization.

Chronic hepatitis B virus infection in Italy during the twenty-first century: an updated survey in 2019.

The aim of this study is to provide updates on the characteristics of chronic HBsAg carriers in Italy before the advent of new drugs eliminating or functionally inactivating the genome HBV reservoirs. HBV endemicity has greatly decreased in Italy over the past decades. A not negligible number of chronic HBsAg carriers are still alive in the country. Chronic HBsAg carriers consecutively referring to 9 units in Italy were prospectively enrolled for a 6-month period in 2019. Multiple logistic regression analysis was performed to identify independent predictors of treatment. A total of 894 cases was recruited (sex ratio 1.6; mean age 53.7 ± 13.5 years). The proportion of subjects born abroad was 19.0%; only 1% of cases reported current heavy alcohol intake (> 4 units/day). Chronic HBV infection, chronic HBV hepatitis, and subjects with liver cirrhosis and/or HCC represented 24.8%, 55%, and 19.3% of cases, respectively. After exclusion of the 222 subjects with chronic HBV infection, the proportion of subjects under therapy was as high as 89.3%. A more severe liver disease (OR 2.52; 95% CI = 1.25-5.14) resulted an independent predictor of the likelihood of treatment; male sex was marginally associated (OR 1.67; 95% CI = 1.02-2.76) to the chance of treatment. People born abroad had same chance than Italians native to be treated (OR 2.12; 95% CI = 0.9-4.97). The high proportion of subjects under treatment and the absence of gender and ethnic barrier against treatment sound good news. These updated figures may represent reference data for evaluating the potential impact of forthcoming new therapy against HBV-related disease.

Risk of HBV infection among male and female first-time blood donors born before and after the July 1986 HBV vaccination program in Taiwan.

BACKGROUND: In July 1984, Taiwan officially began a nationwide hepatitis B virus (HBV) vaccination program where only infants born to HBsAg-positive mothers were vaccinated free of charge until June 1986. However, from July 1986, all infants were vaccinated against HBV. The impact of the July 1986 HBV vaccination program on first-time blood donors has not been exhaustively studied. We, therefore, determined the risk of HBV among male and female first-time blood donors born before and after the July 1986 HBV vaccination program in Taiwan. METHODS: Initially, we recruited 857,310 first-time blood donors whose data were collected between 2013 and 2018 from 5 blood donation centers in Taiwan. However, we excluded donors with incomplete and outlying data (n = 12,213) and those born between July 1984 and June 1986 (n = 21,054). The final study participants comprised 9118 HBV positive and 814,925 HBV negative individuals. We divided the participants into two birth cohorts (born before and after July 1986) and assumed that those born before July 1986 were not vaccinated at birth while those born after July 1986 were vaccinated. RESULTS: The prevalence of HBV among those born before and after July 1986 was 4.53 and 0.25%, respectively. Individuals born after July 1986 had a lower risk of HBV than those born before July 1986. The adjusted odds ratio (OR), 95% confidence interval (CI) was 0.16, 0.13-0.19. Men had a higher risk of HBV than women (OR = 1.40, 95% CI = 1.34-1.47). The interaction between sex and birth date was significant (p-value = 0.0067). Stratification of participants by birth date revealed a higher risk of HBV in men compared to women in both birth cohorts. The OR, 95% CI was 1.47, 1.40-1.55 for those born before July 1986 but declined to 1.15, 1.02-1.29 for those born after July 1986. CONCLUSIONS: The risk of HBV was lower among those born after than those born before the July 1986 vaccination program. In both cohorts, the risk was high in men relative to women. The seemingly protective effect among those born after July 1986 was higher in women than men.

Acceptability of on-site rapid HIV/HBV/HCV testing and HBV vaccination among three at-risk populations in distinct community-healthcare outreach centres: the ANRS-SHS 154 CUBE study.

BACKGROUND: HIV, HBV and HCV infections continue to represent major health concerns, especially among key at-risk populations such as men who have sex with men (MSM), people who inject drugs (PWIDs), transgender women (TGW) and sex workers (SW). The objective of the ANRS-CUBE study was to evaluate the acceptability of a healthcare, community-based strategy offering a triple rapid HIV-HBV-HCV testing, and HBV vaccination, targeted at three priority groups (MSM, PWIDs and TGW/SWs), in three community centers, in the Paris area. METHODS: This longitudinal multicentric non-randomized study included all adult volunteers attending one of the three specialized community centers in Paris, between July 2014 and December 2015. HIV, HBV and HCV status and acceptability of HBV vaccination were evaluated. RESULTS: A total of 3662, MSM, 80 PWIDs and 72 TGW/SW were recruited in the three centers respectively. Acceptability of rapid tests was 98.5% in MSM and 14.9% in TGW/SWs, but could not be estimated in PWIDs since the number of users attending and the number of proposals were not recorded. User acceptability of HBV vaccination was weak, only 17.9% of the eligible MSM (neither vaccinated, nor infected) agreed to receive the first dose, 12.2% two doses, 5.9% had a complete vaccination. User acceptability of HBV vaccination was greater in PWIDs and TGW/SWs, but decreased for the last doses (66.7 and 53.3% respectively received a first dose, 24.4 and 26.7% a second dose and 6.7 and 0% a third dose). Fifty-three participants (49 MSM and 4 PWIDs) were discovered HIV positive, more than half with a recent infection. All but two HIV positive participants were linked to appropriate care in less than one month. CONCLUSIONS: Rapid HIV-HCV-HBV screening showed a very high level of acceptability among MSM. Efforts need to be made to improve immediate acceptability for HBV vaccination, especially among MSM, and follow-up doses compliance. Our results show the important role of community centers in reaching targets, often fragile, populations, while also suggesting the need to reinforce on-site human support in terms of testing and vaccination, especially when addressing PWIDs.

Factors affecting HBV vaccination in a Medical training College in Kenya: A mixed methods Study.

BACKGROUND: Hepatitis B Virus (HBV) is highly endemic in Sub-Saharan Africa with 70 to 90% of the population becoming infected before the age of 40 years. Healthcare workers (HCWs) including healthcare students (HCSs) are at an increased risk of contracting HBV due to occupational exposure. HCSs are especially at a high risk because of their inexperience with infection control procedures and insufficient knowledge about the level of risk when dealing with patients. Despite the availability of an effective vaccine, and its recommendation by Kenya's Ministry of Health, few HCW and students are vaccinated. The aim of this study was to evaluate the influence of awareness, attitude, practices, and access factors on hepatitis B vaccination uptake by HCSs at Kenya Medical Training College (KMTC). METHODS: This was a concurrent mixed methods study. For the quantitative arm, a structured questionnaire was used to assess the awareness, knowledge, attitudes and practices towards HBV disease and vaccination. Accessibility of the HBV vaccine in the participating campuses was also assessed. Two FGDs were carried out: one comprised of student representatives of the participating campuses while the second comprised of members of staff. Quantitative data was analysed using STATA (version 15) while NVIVO (version 11) was used for qualitative data. RESULTS: Out of 634 students invited to participate in the study, 487 participated (response rate 76.8%). Majority of the respondents were from Nairobi Campus (44.2%) and from the Department of Nursing (31.2%). HBV vaccine uptake rate was 85.8% while the non-vaccination rate was 14.3%. Full vaccination was reported by only 20.2% of respondents. The major reason for not receiving the recommended doses was the unavailability of the vaccine when students went for it. The qualitative study revealed challenges in the implementation of the vaccination program at KMTC. CONCLUSIONS: Full vaccination rates remained low despite good knowledge of HBV infection and positive attitude towards vaccination. There is therefore need to streamline vaccination programs in medical colleges to ensure availability and accessibility of the vaccine to healthcare students.

High level of vaccination and protection against hepatitis B with low rate of HCV infection markers among hospital health care personnel in north of Iran: a cross-sectional study.

BACKGROUND: hepatitis B virus (HBV) and C virus (HCV) are among the leading causes of mortality worldwide. Health care personnel (HCP) are subjected to increased risk of these infections. Therefore, HBV vaccination and post-vaccination serologic testing (PVST) are recommended for them. Our objectives in this study were investigate how well the vaccination guidelines for hospital HCPs were implemented. Moreover, the prevalence rates of HBV and HCV infections were calculated. To determine the presence of immunological memory, vaccinated personnel negative to antibody against HB surface antigen with one dose of HB vaccine were boosted. METHODS: From 1 July to 30 November 2017, a cross-sectional study among HCPs working in public hospitals were conducted. All HCPs from various professional categories potentially at risk of exposure to contaminated sources were included. The information was gathered via interview and self-administered questionnaire. The questions were focused on the demographic characteristics, HB vaccination and immunity status and time elapsed since initial vaccination series, and frequency of needelstick injuries during the past 12 months of their work. Moreover, the prevalence rate of HBV and HCV infections were calculated. To determine the presence of immunological memory, subjects negative to HBV seromarkers received a booster dose of the vaccine. RESULTS: A total of 186 out of 766 participants were male and nurses comprised 71% of personnel. Although all HCP were vaccinated, 84% of them completed the course and less than 5% of them received PVST. According to the results, 0.78, 4.6, and 83% were serologically positive to HBV surface antigen, antibodies against HBV core, and S antigens, respectively. Approximately, 91% of seronegative participants responded to a booster dose and only 0.91% of the personnel was anti-HCV positive. CONCLUSION: Most HCP received full HBV vaccination course. Although a minority did PVST, the HBV vaccine-induced long-term protection and HB vaccine booster were not required. Therefore, policies should be made to increase the rate PVST after immunization. According to the results, the HCV infection rate was low and thus pre-recruitment screening was not necessary.

The Impact of Universal Infant Hepatitis B Immunization on Reducing the Hepatitis B Carrier Rate in Pregnant Women.

BACKGROUND: The hepatitis B virus (HBV) status of pregnant women affects HBV vaccine failure in their offspring. This study is aimed to investigate the impact of the universal infant HBV vaccination program on the long-term hepatitis B surface antigen (HBsAg) rate in pregnant women. METHODS: Using the National Immunization Information System, we examined a 32-year period of cross-sectional data on a maternal HBsAg and hepatitis B e antigen (HBeAg) screening program launched in July 1984. An age-period-cohort model analysis of 940 180 pregnant women screened for July 1996-June 1997 and the years 2001, 2006, 2011, and 2016 was applied. RESULTS: The annual HBsAg- and HBeAg-seropositive rates decreased from 13.4% and 6.4%, respectively, for the period 1984-1985 to 5.9% and 1.0% in 2016 (P for both trends < .0001). Pregnant women with birth years after July 1986 (the HBV vaccination cohort) had the lowest relative risk (0.27 [95% confidence interval, .26-.28]) of HBsAg positivity compared with birth years before June 1984. CONCLUSIONS: The birth cohort effect in relation to the universal infant HBV immunization program has effectively reduced the HBV carrier rate in pregnant women and the burden of perinatal HBV infection on the next generation.

Assessment of anti-HBs antibody concentration in children with juvenile idiopathic arthritis treated with biological drugs, vaccinated against viral type B hepatitis in infancy.

OBJECTIVES: The introduction of vaccinations against viral hepatitis B in the years 1994-1996 in Poland significantly improved the epidemiological situation of hepatitis B virus (HBV) infections in our country. According to the report of the National Institute of Public Health - National Institute of Hygiene in 2018, 40 cases of acute hepatitis B were noted while still in the 1980s between 10 and 20 thousand new cases were reported annually. The aim of the study was to determine whether in children treated with biological drugs (adalimumab, etanercept, infliximab) due to juvenile idiopathic arthritis (JIA), vaccinated against hepatitis B in infancy, a protective concentration of anti-HBs antibodies persists. In patients, the value ≥ 10 mIU/ml is regarded as a protective concentration of antibodies, determined at least four weeks after administration of the last vaccine dose. Among healthy individuals, presence of anti-HBs antibodies in any concentration means seroprotection. No booster vaccinations are recommended in basically vaccinated healthy individuals. MATERIAL AND METHODS: The concentrations of anti-HBs antibodies were determined in 56 children with JIA (38 girls - 67.9% and 18 boys - 32.1%) aged from 2 years and 4 months to 17.5 years, treated for at least three months with biological drugs. The diagnosis of JIA was made based on the International League of Associations for Rheumatology (ILAR) criteria. All studied patients were at the stable stage of the disease and received a full course of hepatitis B vaccination during infancy (in accordance with 0,1,6 months injection scheme). RESULTS: In the studied children a protective anti-HBs antibody concentration was found in 34 cases (60.7%), and 22 children (39.3%) had anti-HBs antibody concentration < 10 mIU/ml (in these children no seroprotection was found). CONCLUSIONS: The post-vaccination antibody concentration should be determined in children with JIA, treated with biological drugs and, in case of absence of a protective concentration, revaccination should be started.

Immunogenicity and safety of 4 vs. 3 standard doses of HBV vaccination in HIV-infected adults with isolated anti-HBc antibody.

BACKGROUND: Presence of isolated anti-HBc antibody is common in HIV-infected patients in endemic areas and could be caused by prior HBV infection with loss of anti-HBs antibody. The role of vaccination in these patients remains controversial and is based largely on limited and low quality data. We, therefore, conducted this study to determine immunogenicity and safety of 4 vs. 3 standard doses of HBV vaccination in HIV-infected adults with isolated anti-HBc antibody. METHODS: An open-label, randomized controlled trial was conducted among HIV-infected patients visiting HIV clinic of the Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand between July and September 2017. Inclusion criteria included ≥ 18 years of age, currently on a stable antiretroviral regimen, CD4+ cell count ≥ 200 cells/mm3, plasma HIV-1 RNA < 20 copies/mL, and isolated anti-HBc antibody. The participants were randomized to receive either 3 standard doses (20 µg at month 0, 1, 6) or 4 standard-doses (20 µg at month 0, 1, 2, 6) of IM HBV vaccination, and were evaluated for anamnestic response at week 4 and vaccine response at week 28. RESULTS: Of the 97 patients screened, 54 (32 male, mean age of 46 years) were enrolled and 27 were allocated to each of the vaccination groups. Anamnestic response occurred in 25.9% vs. 33.3% in 3-dose group vs. 4-dose group, respectively (p = 0.551). The vaccine response rates at week 28 were 85.2% in 3-dose group vs. 88.9% in 4-dose group (p = 1.000); geometric mean titer of anti-HBs antibody at week 28 was 63.8 and 209.8 mIU/mL in 3-dose group and 4-dose group, respectively (p = 0.030). No adverse events were reported. CONCLUSIONS: An anamnestic response occurred in one-third of Thai HIV-infected patients with isolated anti-HBc antibody who received one dose of HBV vaccination; however, the majority were still unprotected. The use of either 3 or 4 standard-doses of vaccination was highly effective and should be recommended in all HIV-infected individuals with isolated anti-HBc antibody. Trial registration ClinicalTrials.gov; NCT03212911. Registered 11 July 2019, https://clinicaltrials.gov/ct2/show/NCT03212911.

Incidence of hepatitis B virus infection in young Chinese blood donors born after mandatory implementation of neonatal hepatitis B vaccination nationwide.

This study was carried out to determine the incidence of hepatitis B virus (HBV) infection in the young generation born after mandatory implementation of hepatitis B vaccination since 1992. Repeat blood donors born between 1992 and 1997 were enrolled, who gave blood at least twice during the past 3 years. Donors were tested for HBV infection markers of HBsAg, anti-HBc, anti-HBs and viral DNA by immunoassays (EIAs) and nucleic acid tests (NAT). A total of 14 937 pre-donation screening qualified young repeat donors aged 18-23 years were tested with 9 (0.06%) being HBsAg by EIA and 10 (1:1494) HBV DNA positive by Ultrio NAT (10.4 IU/mL), respectively. HBV DNA was further detected in 1:192 (9/1732) anti-HBc+ repeat donors with Ultrio Plus NAT (3.4 IU/mL). Most cases were identified as occult HBV infection (OBI). Of 14 937 repeat donors, 20.9% were anti-HBc+ positive, while approximately 50% of 12 024 repeat donors were anti-HBs negative or had levels <100 IU/L. HBsAg+ or OBI strains were classified as wild type of genotype B or genotype C. Incident HBV infection in repeat donors was approximately 1:18.5 person-years (1.1%/year) but significantly less frequent in donors with confirmed HBV vaccination (2.4%-3.3%) than those unsure of vaccination status (10.5%; P = .0023). Hepatitis B virus vaccination appears largely protective of HBV infection, but incidence of infections increases in young adults with mostly undetectable or low anti-HBs or occasionally high anti-HBs. A boost of hepatitis B vaccine for adolescents prior to age 18 years may reduce HBV infection, and implementation of more sensitive NAT in blood donation screening may improve HBV safety in blood transfusion.

Influence of universal HBV vaccination on chronic HBV infection in Italy: Results of a cross-sectional multicenter study.

BACKGROUND AND AIM: The universal hepatitis B vaccination for infants and 12-year-old adolescents (the latter limited to the first 12 years of application) was launched in Italy in 1991. Twenty-three years later we evaluated the impact of the vaccination campaign on the burden of HBsAg-positive chronic liver diseases (CLD). MATERIAL AND METHODS: A total of 513 HBsAg-positive chronic carriers referring to 16 Italian liver units were investigated and compared with HBsAg carriers enrolled in previous surveys. RESULTS: The proportion of inactive carriers decreased from 20.0% in 2001 to 3.3% in 2014, while that of cirrhotic patients increased from 22.6% to 33.2%. Regarding the age class 0-33 (fully covered by HBV vaccination in 2014), the rate of inactive carriers decreased from the 21.7% in 2001 to 5.9% in 2014, that of chronic hepatitis from 17.5% to 5.2% and that of cirrhosis cases from 26.4% to 4.1%. Instead, in the over-60 age group the rate of inactive carriers increased from 22.8% to 41.2% and that of chronic hepatitis from 16.8% to 46%; the rate of patients with cirrhosis ranged from 5% to 8% in different studies. CONCLUSION: Twenty-three years after the introduction universal HBV vaccination in Italy, the clinical presentation of CLD had shown a shift toward older ages and more severe diseases.

Slow decline of hepatitis B burden in general population: Results from a population-based survey and longitudinal follow-up study in Taiwan.

BACKGROUND & AIMS: Hepatitis B virus (HBV) infection poses a global public health threat. HBV vaccination has proven highly effective in preventing the infection; however, its long-term impact on the general population has not been addressed. We conducted analysis to determine the total and changing burden of chronic HBV infection and evaluate the serological status between vaccinated and unvaccinated in Taiwan. METHODS: Participants in "The Taiwanese Survey on Prevalence of Hyperglycemia, Hyperlipidemia and Hypertension" in 2002 (n=6602), and 4088 with follow-up survey in 2007 were included. HBsAg (including titers), anti-HBs, anti-HBc, HBeAg, anti-HBe, HBV genotypes and viral loads were assayed. Prevalence and evolving patterns of these seromarkers was compared between vaccinated and unvaccinated cohorts and predictors of persistent HBsAg positivity and negativity were examined. RESULTS: The overall prevalence of chronic HBV infection was 13·7% (95% CI, 12.9% to 14.5%) and about two thirds had past exposure (anti-HBc: 68·46%) in 2002. The vaccinated cohort tended to have lower prevalence of HBsAg and anti-HBc, and a higher proportion of anti-HBs and HBeAg positivity, genotype C and high viral load. The majority (85·42%) were consistently HBsAg negative while 12·65% were consistently positive, and 8·98% achieved seroclearance in a five-year period. In the vaccinated cohort, no subjects had acquired new exposure and became HBsAg positive, and only one (0.54%) cleared HBsAg, demonstrating the durability of vaccination through teenage and young adulthood. CONCLUSIONS: This comprehensive, population-representative-survey shows that 20 years after universal vaccination, the backlog still composed a substantial burden of chronic HBV infections in Taiwan.

Serosusceptibility and hesitancy for booster HBV vaccination among health care workers in Italy: A cross-sectional study.

BACKGROUND: Health care workers (HCWs) are at increased risk of exposure to hepatitis B virus (HBV). The most effective prevention measure is vaccination, with a serum hepatitis B surface antibody (HBsAb) titre > 10 mIU/ml considered protective. To date, the sociodemographic and occupational characteristics related to HBV serosusceptibility and factors associated with booster hesitancy remain unclear. Therefore, this study aimed to identify factors associated with maintaining a protective HBsAb titre in a large sample of HCWs and to evaluate factors potentially associated with hesitancy towards vaccine boosters. METHODS: A cross-sectional study was conducted among HCWs who underwent a health surveillance visit between 2017 and 2022. If the serum HBsAb titre was < 10 MIU/ml, a vaccine booster dose was offered. Based on their willingness to be vaccinated, employees were classified into three groups: acceptance, hesitation, and refusal. Uni- and multivariable analyses were performed to assess the association of demographic and occupational characteristics with serosusceptibility and attitudes towards vaccination. RESULTS: A total of 1632 (27%) employees were shown to be nonimmune. A lower median age and being a physician were significantly associated with a protective HBsAb titre. A total of 706 nonimmune employees (43.3%) accepted the vaccination, 865 (53%) hesitated, and 61 (3.7%) refused. The median age of those who refused vaccination was significantly higher than that of those who hesitated and those who were vaccinated. Acceptance of vaccination was significantly higher among nurses, while nurse aides hesitated more; among nonmedical graduate staff both hesitation and refusal were higher than expected. In the multivariable analysis, higher age, female sex, and employment as an allied health care professional were shown to be significantly associated with hesitation/refusal, while being born abroad turned out to be protective. CONCLUSIONS: Our study showed that approximately a quarter of HCWs were not immune to HBV infection, and of these, more than half were hesitant towards or refused the booster dose. The risk of hesitation/refusal was higher with age in women and among allied health care staff. Based on these findings, further studies are needed to prospectively evaluate HBV seroprevalence, vaccination adherence, factors associated with hesitancy, and the effectiveness of health surveillance strategies in a high-risk population susceptible to infection.

Renal transplantation from hepatitis B surface antigen (HBsAg)-positive donors to HBsAg-negative recipients: a case of post-transplant fulminant hepatitis associated with an extensively mutated hepatitis B virus strain and review of the current literature.

PURPOSE: The purpose of this study was to present a fatal case of fulminant hepatitis B (FHB) that developed in a renal transplant recipient, immunized against hepatitis B, 1 year post transplantation. METHODS: Polymerase chain reaction amplification and full genome sequencing were performed to investigate whether specific mutations were associated with hepatitis B virus (HBV) transmission and FHB. RESULTS: Molecular analysis revealed multiple mutations in various open reading frames of HBV, the most important being the G145R escape mutation and a frameshift mutation-insertion (1838insA) within the pre-C/C reading frame. CONCLUSIONS: Our results highlight the possibility of developing FHB, despite previous immunization against HBV or administration of hyperimmune gammaglobulin, because of the selection of escape virus mutants. The current literature and guidelines regarding renal transplantation from hepatitis B surface antigen (HBsAg)-positive to HBsAg-negative patients were also reviewed.