Search Results (59)

Background: This study aims to analyze the vaccination status and factors influencing delayed vaccination among toddlers born to hepatitis B surface antigen (HBsAg)-positive mothers. Methods: Data of HBsAg-positive mothers between 1 January 2021 and 31 December 2022 were provided by the Suzhou Maternal and Child Health Care and Family Planning Service Center. The vaccination records were obtained from the Jiangsu Province Immunization Service Management Information System. Logistic regression analysis was used to analyze influencing factors of delayed vaccination. Results: A total of 4250 toddlers born to HBsAg-positive mothers were documented. The data revealed that the first dose of the hepatitis B vaccine was administered to 100% of the toddlers. In addition, the coverage of the National Immunization Program (NIP) vaccines among these toddlers ranged from 92.9% to 99.4%. The proportion of delayed NIP vaccination varied between 0% and 12.2%. The proportion of delayed Bacillus Calmette–Guérin (BCG) vaccination was 11.3%, with the delay predominantly observed between 4 and 6 months. Notably, the proportion of delayed BCG vaccination among the toddlers born to HBsAg-positive mothers was significantly higher than that in the general population. Additionally, the proportion of the first dose of non-NIP vaccines was 3.3–36.4%, and the proportion of DTaP-IPV/Hib was 27.0%. Logistic regression analysis revealed that the regional level, the mother’s human papillomavirus (HPV) vaccination status, and the infant’s birth weight were significant factors influencing the timeliness of vaccination. Conclusions: Although the vaccination status of toddlers born to HBsAg-positive mothers in Suzhou city remains stable, the issue of delayed vaccination requires attention. It is essential to continue strengthening targeted vaccine education to reduce vaccine hesitancy and improve the rate of timely vaccination. Full article

Background: Hepatitis B (HBV) and Delta (HDV) virus infections pose critical public health challenges, particularly in Romania, where HDV co-infection is underdiagnosed. Methods: This study investigates the epidemiology, risk factors, and clinical outcomes of HBV/HDV co-infection in vulnerable populations, leveraging data from the LIVE(RO2) program. Conducted between July 2021 and November 2023, the program screened 320,000 individuals across 24 counties, targeting socially disadvantaged groups such as rural residents, the Roma community, and those lacking health insurance. Results: Among 6813 hepatitis B surface antigen (HBsAg)-positive individuals, HDV antibody prevalence was 4.87%, with active replication confirmed in 75.6% of HDV-positive cases. Regional disparities emerged, with higher HDV prevalence and replication rates in the Eastern region compared to the South. HDV-positive individuals were more likely to be younger, male, and from rural or socioeconomically disadvantaged backgrounds. Clinically, HDV co-infection correlated with increased liver stiffness, advanced fibrosis stages, and lower steatosis levels compared to HBV mono-infection. Psychiatric comorbidities were more prevalent among HDV-positive patients, highlighting the need for integrated care. Conclusions: This study underscores the urgent need for targeted public health interventions, including enhanced screening, education, and access to novel antiviral therapies like bulevirtide to address the significant burden of HBV/HDV co-infection in Romania. Full article

Objectives: This study aimed to evaluate the risk of hepatitis B virus reactivation (HBVr) in COVID-19 patients receiving immunosuppressive treatment, which has been insufficiently studied to date. Secondarily, we aimed to evaluate the seroprevalence of HBV infection in COVID-19 patients. Methods: We performed HBV screening on all Romanian adults hospitalized in four COVID-19 wards between October 2021 and September 2022. We enrolled patients with positive hepatitis B core antibody (anti-HBc) without protective hepatitis B surface antibody (anti-HBs), HBV treatment, or baseline immunosuppressive conditions, and we conducted a virological follow-up on these patients at 3 months. Results: We identified 333/835 (39.9%) anti-HBc-positive patients. Follow-up was performed for 13 patients with positive hepatitis B surface antigen (HBsAg) and 19 HBsAg-negative/anti-HBc-positive patients. Among those who received immunosuppressants, 4/23 (17.4%) patients experienced HBVr: 1 out of 8 (12.5%) HBsAg-positive patients (with 1.99 log increase in HBV DNA level) and 3 out of 15 (20%) HBsAg-negative/anti-HBc-positive patients (with a de novo detectable HBV DNA level). Conclusions: Administration of COVID-19 immunosuppressants may result in a significant risk of HBVr in co-infected patients. We recommend performing an HBV triple screen panel (HBsAg, anti-HBs, anti-HBc) for all COVID-19 patients receiving immunosuppressive treatment. HBV prophylaxis may be indicated in certain patients. Larger studies are needed in order to establish appropriate and cost-effective management for these patients. Full article

This study aims to characterize the molecular profile of the hepatitis B virus (HBV) among socially vulnerable immigrants residing in Brazil to investigate the introduction of uncommon HBV strains into the country. Serum samples from 102 immigrants with positive serology for the HBV core antibody (anti-HBc) were tested for the presence of HBV DNA by PCR assays. Among these, 24 were also positive for the HBV surface antigen (HBsAg). The full or partial genome was sequenced to determine genotype by phylogenetic analysis. Participants were from Haiti (79.4%), Guinea-Bissau (11.8%), Venezuela (7.8%), and Colombia (1%). Of the 21 HBV DNA-positive samples, subgenotypes A1 (52.4%), A5 (28.6%), E (9.5%), F2 (4.8%), and F3 (4.8%) were identified. Among the 78 HBsAg-negative participants, four were positive for HBV DNA, resulting in an occult HBV infection rate of 5.1%. Phylogenetic analysis suggested that most strains were likely introduced to Brazil by migration. Importantly, 80% of A5 sequences had the A1762T/G1764A double mutation, linked to an increased risk of hepatocellular carcinoma development. In conclusion, this study is the first report of HBV subgenotype A5 in Brazil, shedding new light on the diversity of HBV strains circulating in the country. Understanding the genetic diversity of HBV in immigrant communities can lead to better prevention and control strategies, benefiting both immigrants and wider society. Full article

Hepatitis delta virus (HDV) is a satellite of hepatitis B virus (HBV), which requires the HBV surface antigen (HBsAg) for its assembly and propagation. Although countries affected by HBV infection in Africa are well identified, data on HDV infection are still scarce, like in Nigeria, where HBV infection is endemic. In this study, we aimed to determine the prevalence of HDV infection and identify the circulating genotypes/strains in the country. A nationwide study was performed on 1281 HBsAg-positive samples collected from patients across eleven sites drawn from the six geopolitical zones in Nigeria. Anti-HDV antibody (HDV-Ab) screening and HDV-RNA viral load quantification were performed using a commercial ELISA assay and real-time RT-PCR kit, respectively. HDV genotyping was performed by the Sanger sequencing of amplicons from the so-called R0 region of the viral genome, followed by phylogenetic analyses. Of the 1281 HBsAg-positive samples, 61 (4.8%) were HDV-Ab positive, among which, 12 (19.7%) were HDV-RNA positive. Genotypes were obtained for nine of them: seven “African” HDV-1, one “Asian/European” HDV-1 and one HDV-6. This study shows that Nigeria is a country of low HDV prevalence where mainly “African” genotype-1 strains are circulating. Full article

HIV-1, Hepatitis B and HTLV-1 have similar risk factors and shared routes of transmission and MSM are disproportionately affected by HIV. The aim of the study was to determine the prevalence of HTLV-1 and HBsAg positivity at initial enrolment among MSM attending a large HIV Clinic in Trinidad. Chart reviews were conducted between 2 and 15 January 2024, among self-identified MSM and a comparative group of randomly selected self-identified heterosexual males where sociodemographic, clinical and laboratory data were collected and analysed using SPSS Version 25. During the period April 2002–31 October 2023, in total there were 10,424 patients registered at the clinic, of whom 1255 (12.0%) were self-identified MSM, with an age range of 19–85 years and a median age of 40 years. There were 1822 randomly selected heterosexual males, with an age range of 18–94 years old and a median age of 52 years. Among the MSM, there were 21 (1.67%) patients who were HIV-1/HTLV-1-coinfected, 64 (5.10%) who were HIV-1/HBsAg-coinfected and two (0.16%) who were coinfected with all three viruses (HIV-1/HTLV-1/HBsAg) as compared to 47 ((2.58%) HIV-1/HTLV-1-coinfected (p = 0.12), 69 (3.79%) HIV-1/HBsAg-coinfected (p = 0.10) and three (0.16%) patients coinfected with all three viruses among the heterosexual males. There were no patients with HTLV-1-related diseases among the HIV-1/HTLV-1-coinfected patients and there were no deaths from chronic liver disease in patients coinfected with HIV-1/HBsAg. Despite the availability of an efficacious vaccine, there is a prevalence of hepatitis B of 5.1% among MSM attending the HIV Clinic in Trinidad; therefore, programmes to increase health literacy, screening and immunization are urgently needed. Full article

(1) Background: Hepatitis B virus (HBV) sequencing data are important for monitoring HBV evolution. We aimed to molecularly characterize HBV sequences from participants with HBV surface antigen-positive (HBsAg+) serology and occult hepatitis B infection (OBI+). (2) Methods: We utilized archived plasma samples from people living with human immunodeficiency virus (PLWH) in Botswana. HBV DNA was sequenced, genotyped and analyzed for mutations. We compared mutations from study sequences to those from previously generated HBV sequences in Botswana. The impact of OBI-associated mutations on protein function was assessed using the Protein Variation Effect Analyzer. (3) Results: Sequencing success was higher in HBsAg+ than in OBI+ samples [86/128 (67.2%) vs. 21/71 (29.2%)]. Overall, 93.5% (100/107) of sequences were genotype A1, 2.8% (3/107) were D3 and 3.7% (4/107) were E. We identified 13 escape mutations in 18/90 (20%) sequences with HBsAg coverage, with K122R having the highest frequency. The mutational profile of current sequences differed from previous Botswana HBV sequences, suggesting possible mutational changes over time. Mutations deemed to have an impact on protein function were _tpQ6H, _surfaceV194A and _preCW28L. (4) Conclusions: We characterized HBV sequences from PLWH in Botswana. Escape mutations were prevalent and were not associated with OBI. Longitudinal HBV studies are needed to investigate HBV natural evolution. Full article

(1) Background: we determined the prevalence of the hepatitis B virus (HBV) amongst people without human immunodeficiency virus (HIV) in rural and peri-urban areas in Botswana. (2) Methods: We screened for the hepatitis B surface antigen (HBsAg) from archived plasma samples of people without HIV (n = 2135) randomly selected from the Botswana Combination Prevention Program (BCPP) (2013–2018). We sequenced 415 bp of the surface region using BigDye sequencing chemistry. (3) Results: The median age of participants was 31 (IQR: 24–46) and 64% (1360/2135) were female. HBV prevalence was 4.0% (86/2135) [95% CI: 3.3–4.9]) and ranged between 0–9.2%. Older participants (>35 years) had increased odds of HBV positivity (OR: 1.94; 95% CI: [1.32–2.86]; p = 0.001). Thirteen samples were sequenced and seven (53.8%) were genotype A, three (23.1%) were genotype D and genotype E each. Clinically significant mutations were identified in the surface region, but no classic drug resistance mutations were identified. (4) Conclusions: We report an HBV prevalence of 4.0% (95% CI 3.3–4.9) among people without HIV in rural and peri-urban communities in Botswana with varying rates in different communities. A comprehensive national HBV program is required in Botswana to guide HBV prevention, testing and management. Full article

Several antiviral treatment regimens for chronic hepatitis B (CHB) virus infection have been shown to be effective in suppressing viral load and reducing the risk of hepatocellular injury and its complications. It has been hypothesized that high levels of circulating HBV surface antigen(s) may lead to immune tolerance against HBV and contribute to chronic carriership. Conversely, low-level HBsAg may create a window for the reconstitution of an HBV-specific immune response through vaccination and control of infection. Previous studies in non-responders to yeast-derived HBV vaccines, using a third-generation pre-S/S vaccine, have led to up to 95% anti-HBs seroconversion. This report evaluates the long-term outcome after experimental vaccination with a pre-S/S HBV vaccine intended as a therapeutic intervention in chronic HBV carriers. Four low-level HBsAg carriers (<500 IU/mL) were vaccinated three to seven times with 20 μg PreHevbrio^R. Three out of four carriers eliminated HBsAg completely and seroconverted to anti-HBs. One patient seroconverted to anti-HBs but remained with a borderline HBsAg titer (10 IU/mL). Serum anti-HBs levels following repeated vaccination varied between 27 and >1000 IU/L, respectively. Long-term observation (>6 years) showed that after discontinuing NUC treatment for at least two years, HBsAg and HBV DNA remained negative with anti-HBs positive titers ranging between 80 and >1000 IU/L. Based on our preliminary observations, there is a rationale to further evaluate the role of this vaccine as a therapeutic agent. Full article

Background and Objectives: Hepatitis B (HB) is a major global health problem and a potentially life-threatening disease caused by the hepatitis B virus (HBV). Also, it is an important cause of morbidity and mortality worldwide. Thanks to serological surveys, testing hepatitis B surface antibodies (anti-HBs) allows for serological assessments of their prevalence. The presence of anti-HBs, which protects against HBV infection, can be attributed to HB vaccination or natural HBV infection. The aim of our study was to evaluate the prevalence of HB surface antibodies (anti-HBs) as an indicator of collective immunity against HBV in the general population of the Autonomous Province of Vojvodina, Serbia. In addition, to distinguish whether anti-HBs were induced by the vaccine or by infection, the presence of antibodies against the hepatitis B core antigen (anti-HBc) was tested among those who were anti-HBs-positive. Materials and Methods: A total of 3467 residual sera samples, collected according to the specifications of the European Sero-Epidemiology Network 2 (ESEN2) study, from April 2015 to March 2016, were screened for the presence of anti-HBs using a chemiluminescence immunoassay. The difference between categorical variables was tested using the chi-square test. Results: Overall, 1870 (53.9%, 95% CI: 52.3–55.6) participants tested positive for anti-HBs. The median age of the study participants was 17 years (IQR 9–35). The anti-HB seroprevalence decreased with age, ranging from 80.7% (95% CI: 78.9–82.4) in the 1–19-year-old group to 16.4% (95% CI: 12.0–20.9) in the ≥60 years’ age group. A total of 71 (3.8%, 95% CI: 2.9–4.7) serum samples were also anti-HBc-positive. Higher prevalence, but not statistically significant, was noticed in women (4.1%, 95% CI: 2.8–5.4) compared with men (3.5, 95% CI: 2.4–4.8) (p = 0.542). Also, there was a significant difference across the age groups, where those ≥60 years old had a prevalence of 65.9% (95% CI: 51.9–79.9) and the age category of 1–19-year-olds had just 0.2% (95% CI: 0.0–0.4) (p < 0.001). Conclusions: This study provides a comprehensive assessment of the anti-HBs seroprevalence of the general population in Vojvodina and provides an opportunity to better shape the national preventive strategy related to HBV. Full article

Pregnant women identified to carry hepatitis B surface antigen (HBsAg) should be linked to care for the determination of the need for long-term antiviral therapy (LTT). We assessed the performance of simplified criteria, free from HBV DNA quantification, to select women eligible for LTT using different international guidelines as a reference. A retrospective analysis of HBV-infected pregnant women enrolled in the phase 4 ANRS TA-PROHM study was conducted in Cambodia. Sensitivity, specificity, and AUROC were computed to compare three simplified criteria (TREAT-B, HBcrAg/ALT, and TA-PROHM) with the American (AASLD) and European (EASL) guidelines as a reference. An additional assessment was performed at 6 months postpartum. Of 651 HBsAg-positive women, 209 (32%) received peripartum antiviral prophylaxis using tenofovir disoproxil fumarate (TDF). During pregnancy, 9% and 12% of women were eligible for LTT according to AASLD and EASL guidelines, respectively; 21% and 24% of women were eligible for prophylactic TDF and 2% and 5% in those ineligible (p < 0.001). Using the AASLD guidelines, the AUROC of TREAT-B, HBcrAg/ALT, and TA-PROHM scores were 0.88 (95%CI, 0.85–0.90), 0.90 (95%CI, 0.87–0.92), and 0.76 (95%CI, 0.73–0.80), respectively. Using the EASL guidelines, the AUROCs were lower: 0.73 (95%CI, 0.69–0.76), 0.76 (95%CI, 0.73–0.80), and 0.71 (95%CI, 0.67–0.74), respectively. Among those ineligible for prophylactic TDF, only 2% to 6% present an indication for LTT at 24 weeks postpartum. Few pregnant women are eligible for LTT, and the use of simplified criteria could represent an efficient triage option in decentralized areas to identify those negative for whom there is no urgent indication for LTT and focus on those positive for whom other exams must be conducted to confirm LTT indication. Full article

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, with low rates of early diagnosis and surgical resection. In recent years, with the rapid development of liquid biopsy technology, circulating tumor DNA (ctDNA) has emerged as a research hotspot in the field of precision medicine for liver cancer. Existing studies have demonstrated the suitability of ctDNA for combined detection with other liver cancer diagnostic markers, enabling a multi-index analysis. In recent years, a novel prediction model has been developed for early liver cancer screening based on ctDNA liquid biopsy, M2P-HCC (methylation, mutation, and protein-HCC), mainly incorporating methylation changes, gene mutations, and protein markers associated with liver cancer. Preliminary validation in the HCCscreenTM Investigational (HIT, ChiCTR1800020233) study, which focused on screening early liver cancer in communities with Hepatitis B surface antigen (HBsAg) positivity, yielded promising results with 100% sensitivity and 94% specificity. However, it remains uncertain whether M2P-HCC can be effectively applied in high-risk populations for Hepatitis B-associated liver cancer, warranting further research. Methods: Patients who were under long-term follow-up at the outpatient clinic of the Infectious Diseases Center of West China Hospital of Sichuan University from December 2020 to January 2023 were recruited in this prospective observational study and underwent the M2P-HCC test. The study population consisted of high-risk patients with Hepatitis B-related liver cancer who met the inclusion criteria. Patients with a history of previous malignancy, recent blood transfusion, autoimmune diseases, and human immunodeficiency virus (HIV) infection were excluded. Clinical data were collected at a baseline, and all patients underwent the M2P-HCC blood test. Based on the test results, they were categorized into positive, early-warning, and negative groups. Prospective cohort observation and regular follow-ups were performed for 6–8 months. Results: 313 patients met the inclusion criteria and were included in the study. After 6–8 months of follow-up, HCC occurred in 41(13.1%) participants. The M2P-HCC test demonstrated good predictive performance with an area under the curve (AUC) of 0.88 (95% CI: 0.81–0.95, p < 0.001) and a cutoff value of 83 points (sensitivity 82.9% and specificity 85.7%). In contrast, the combination of alpha-fetoprotein (AFP) and ultrasound (US) yielded an inferior predictive performance (AUC 0.76 (95% CI: 0.69–0.84, p < 0.001), sensitivity 58.5%, and specificity 94.1%). Multivariate analyses revealed that M2P-HCC was an independent predictor of increased risk of HCC (OR = 1.16 [1.09–1.22], p < 0.001). Conclusions: M2P-HCC liquid biopsy demonstrated good performance for early liver cancer screening in high-risk populations of Hepatitis B-related liver cancer, exhibiting better sensitivity than the combination of AFP and US. Full article

(1) Background: Hepatitis B core antibodies (anti-HBc) are a marker of hepatitis B virus (HBV) exposure; hence, a normal HBV serology profile is characterized by HBV surface antigen (HBsAg) and anti-HBc positivity. However, atypical HBV serologies occur, and we aimed to determine the prevalence of an atypical profile (HBsAg+/anti-HBc-) in a cohort of people with HIV-1 (PWH) in Botswana. (2) Methods: Plasma samples from an HIV-1 cohort in Botswana (2013–2018) were used. The samples were screened for HBsAg and anti-HBc. Next-generation sequencing was performed using the GridION platform. The Wilcoxon rank-sum test and Chi-squared tests were used for the comparison of continuous and categorical variables, respectively. (3) Results: HBsAg+/anti-HBc- prevalence was 13.7% (95% CI 10.1–18.4) (36/263). HBsAg+/anti-HBc- participants were significantly younger (p < 0.001), female (p = 0.02) and ART-naïve (p = 0.04) and had a detectable HIV viral load (p = 0.02). There was no statistically significant difference in the number of mutations observed in participants with HBsAg+/anti-HBc- vs. those with HBsAg+/anti-HBc+ serology. (4) Conclusions: We report a high HBsAg+/anti-HBc- atypical serology profile prevalence among PWH in Botswana. We caution against HBV-testing algorithms that consider only anti-HBc+ samples for HBsAg testing, as they are likely to underestimate HBV prevalence. Studies to elucidate the mechanisms and implications of this profile are warranted. Full article

Chronic hepatitis B virus (HBV) infection is a global health threat. Mutations in the surface antigen of HBV (HBsAg) may alter its antigenicity, infectivity, and transmissibility. A patient positive for HBV DNA and detectable but low-level HBsAg in parallel with anti-HBs suggested the presence of immune and/or diagnostic escape variants. To support this hypothesis, serum-derived HBs gene sequences were amplified and cloned for sequencing, which revealed infection with exclusively non-wildtype HBV subgenotype (sgt) D3. Three distinct mutations in the antigenic loop of HBsAg that caused additional N-glycosylation were found in the variant sequences, including a previously undescribed six-nucleotide insertion. Cellular and secreted HBsAg was analyzed for N-glycosylation in Western blot after expression in human hepatoma cells. Secreted HBsAg was also subjected to four widely used, state-of-the-art diagnostic assays, which all failed to detect the hyperglycosylated insertion variant. Additionally, the recognition of mutant HBsAg by vaccine- and natural infection-induced anti-HBs antibodies was severely impaired. Taken together, these data suggest that the novel six-nucleotide insertion as well as two other previously described mutations causing hyperglycosylation in combination with immune escape mutations have a critical impact on in vitro diagnostics and likely increase the risk of breakthrough infection by evasion of vaccine-induced immunity. Full article

A neonatal vaccination against the Hepatitis B virus (HBV) infection was initiated in Russia 20 years ago, with catch-up immunization for adolescents and adults under the age of 60 years launched in 2006. Here, we have assessed the humoral immunity to HBV in different regions of Russia, as well as the infection frequency following 20 years of a nationwide vaccination campaign. We have also evaluated the role of immune-escape variants in continuing HBV circulation. A total of 36,149 healthy volunteers from nine regions spanning the Russian Federation from west to east were tested for HBV surface antigen (HBsAg), antibodies to HBV capsid protein (anti-HBc), and antibodies to HBsAg (anti-HBs). HBV sequences from 481 chronic Hepatitis B patients collected from 2018–2022 were analyzed for HBsAg immune-escape variants, compared with 205 sequences obtained prior to 2010. Overall, the HBsAg detection rate was 0.8%, with this level significantly exceeded only in one study region, the Republic of Dagestan (2.4%, p < 0.0001). Among the generation vaccinated at birth, the average HBsAg detection rate was below 0.3%, ranging from 0% to 0.7% depending on the region. The anti-HBc detection rate in subjects under 20 years was 7.4%, indicating ongoing HBV circulation. The overall proportion of participants under 20 years with vaccine-induced HBV immunity (anti-HBs positive, anti-HBc negative) was 41.7% but below 10% in the Tuva Republic and below 25% in the Sverdlovsk and Kaliningrad regions. The overall prevalence of immune-escape HBsAg variants was 25.2% in sequences obtained from 2018–2022, similar to the prevalence of 25.8% in sequences collected prior to 2010 (p > 0.05). The population dynamics of immune-escape variants predicted by Bayesian analysis have remained stable over the last 20 years, indicating the absence of vaccine-driven positive selection. In contrast, the wild-type HBV population size experienced a rapid decrease starting in the mid-1990s, following the introduction of mass immunization, but it subsequently began to recover, reaching pre-vaccination levels by 2020. Taken together, these data indicate that it is gaps in vaccination, and not virus evolution, that may be responsible for the continued virus circulation despite 20 years of mass vaccination. Full article