Identifying Childhood Risk Factors for Hepatitis B with a Focus on Vertical Transmission.

BACKGROUND: Despite worldwide vaccination efforts, Hepatitis B virus (HBV) infection remains a significant global health burden, particularly in regions where vertical transmission is prevalent. Given Romania's history as an endemic area for hepatitis B from the 1990s until the early 2000s and the previously high infection rates among children, it is crucial to continually evaluate HBV infection in this population to monitor current trends, assess the long-term impact of vaccination programs, and address any remaining gaps in prevention and treatment efforts. This study aims to identify childhood risk factors associated with HBV acquisition, examining the role of maternal HBV status in child HBV infection, focusing on vertical transmission among a cohort of 654 children, with maternal infection as the independent variable and child infection as the dependent variable. METHODS: We assessed potential risk factors and vaccination coverage among these children. The cohort included 148 children who tested positive for chronic hepatitis B from those 654 tested for HBsAg. Anamnestic data and vaccination history were analyzed, with particular attention to birth type and surgical interventions. RESULTS: Of the 148 HBV-positive children, 80.4% were delivered naturally. Among these, 130 had received hepatitis B vaccination, and 5 were also given hepatitis B immunoglobulin at birth, 4 of whom were born via cesarean section. In the control group, comprising 418 vaccinated children, a lesser proportion were unvaccinated (2.2%). Documented surgical interventions included general and dental surgeries, as well as a single blood transfusion. CONCLUSIONS: The study emphasizes the need for comprehensive vaccination strategies and illuminates potential correlations between birth type and vaccination status with childhood HBV infection. Crucially, it highlights the necessity of diligent monitoring and treatment of pregnant women with HBV to prevent vertical transmission as effectively as possible.

HLA Genetic Diversity and Chronic Hepatitis B Virus Infection: Effect of Heterozygosity Advantage.

This research aims to determine whether HLA heterozygosity confers a protective effect against hepatitis B virus infection by analyzing the relationship between HLA diversity and the risk of hepatitis B virus (HBV) infection. A total of 327 hepatitis B patients were selected and categorized based on their clinical status: 284 patients with chronic HBV infection and 43 patients with HBV-related liver cirrhosis (LC). The control group included 304 healthy individuals. HLA genotyping for 11 loci, including HLA class I and class II, was conducted using next-generation sequencing. The results of this study indicate a statistically significant negative correlation between HLA class II heterozygosity and the risk of HBV infection. Specifically, heterozygosity in HLA-DQB1 (OR = 0.49, 95% CI = 0.31-0.76, p = 0.01277) and HLA-DRB1 (OR = 0.42, 95% CI = 0.24-0.77, p = 0.01855) were significantly associated with protection. Subgroup analysis was conducted to explore the effect of HLA diversity among pathological subtypes (chronic hepatitis B and control group, liver cirrhosis and control group). For liver cirrhosis, compared with the control group, a decreased risk of LC was possibly associated with the heterozygosity of HLA class I locus B (OR = 0.24, 95% CI = 0.09-0.65, p = 0.0591), but this hypothesis was not confirmed by other studies. The diversity of HLA, measured by HLA heterozygosity, was associated with a protective effect against HBV infection.

Analysis of hepatitis B Virus Test results among blood donors in Chongqing, China.

BACKGROUND: Hepatitis B virus (HBV) infection is a major concern regarding blood safety in countries with a high HBV prevalence, such as China. We aimed to understand the prevalence of HBV infection among blood donors in Chongqing and provide an important basis for developing appropriate blood screening strategies. METHODS: Dual enzyme-linked immunosorbent assays (ELISAs) for hepatitis B surface antigen (HBsAg) were conducted in parallel with nucleic acid testing (NAT) of donors. All HBsAg-reactive and/or HBV DNA-positive blood samples were tested for HBsAg and hepatitis B DNA levels. RESULTS: A total of 117,927 blood donor samples were collected from the Chongqing Blood Center between April 2020 and November 2020. In total, 473 HBV-ineligible samples were retained for HBsAg and DNA confirmation. A total of 272 samples were confirmed to be HBsAg+, including 2 HBV DNA - and 270 HBV DNA + samples. A total of 201 donations were HBsAg-, including 72 HBV DNA - samples. The rate of HBV infection was 65.33% (309/473) in men, which was significantly higher than that in women (p < 0.001). The HBV failure rate was higher among the first-time donors (p < 0.05). Of the 182 NAT R/HBsAg N/N samples (Nucleic acid test reactivity/2 anti-HBsAg tests negative), 37.91% (69/182) were false positives. The proportion of hepatitis B infections in the 18 NAT R/HBsAg N/R (Nucleic acid test reactivity/1 anti-HBsAg tests negative) samples was 94.44% (17/18), of which 50% (9/18) were occult HBV infection. A total of 95.83% (69/72) of the false positives were from the NAT R/HBsAg N/N group, and 58.33% (42/72) were first-time donors. CONCLUSION: Our data showed a strikingly high HBV infection rate among blood donors in Chongqing. Double ELISA and single NAT can effectively prevent HBV leakage and improve blood safety. First-time donors have a high rate of HBV transplant failure; therefore, donors should be retained and recruited from low-risk groups.

Sociodemographic and clinical features related to hepatitis B virus infection among rejected blood donors in Luanda, Angola.

Background: Hepatitis B virus (HBV) remains a public health concern. Blood donors screened for HBV surface antigen (HBsAg) along with aspartate transaminase (AST)/alanine aminotransferase (ALT) could play a key in providing safe blood products. We investigated the features related to HBV infection among rejected blood donors in Luanda, Angola. Methods: This was a cross-sectional study conducted with 164 rejected donors. Donors were screened for HBsAg from March to May 2022. Overall, 63.4% tested positive for HBV. Results: The mean age of the HBV-positive (29.2 ± 8.02) was lower than the HBV-negative (33.9 ± 10.0) (p < 0.001). Donors between 20 and 40 years (odds ratio [OR]: 2.34, p = 0.045), females (OR: 1.40, p = 0.516), residents in urbanized areas (OR: 1.23, p = 0.530), low educational (OR: 1.54, p = 0.458), unemployed (OR: 1.65, p = 0.271), and unmarried (OR:1.41, p = 0.616) might be likely to contract HBV. AST/ALT ratio was higher in HBV-infected (2.07 ± 1.42) than in HBV-uninfected (1.90 ± 1.14). About 20% of HBV-positive were classified as having acute liver disease, while 80% with chronic liver disease, based on AST/ALT ratio. Age ranged from 20 to 40 years (OR: 1.97, p = 0.305), females (OR: 1.61, p = 0.557), donors from non-urbanized (OR: 1.69, p = 0.557), a low educational (OR: 1.64, p = 0.571), and unemployed donors (OR: 1.81, p = 0.289) were likely to develop chronic liver disease. Conclusions: Our findings indicated the failure of viral hepatitis control measures. Authorities should consider including HBV nucleic acid testing to ensure early identification of HBV in Angola.

HBcrAg values may predict virological and immunological responses to pegIFN-α in NUC-suppressed HBeAg-negative chronic hepatitis B.

OBJECTIVE: Selected populations of patients with chronic hepatitis B (CHB) may benefit from a combined use of pegylated interferon-alpha (pegIFN-α) and nucleos(t)ides (NUCs). The aim of our study was to assess the immunomodulatory effect of pegIFN-α on T and natural killer (NK) cell responses in NUC-suppressed patients to identify cellular and/or serological parameters to predict better T cell-restoring effect and better control of infection in response to pegIFN-α for a tailored application of IFN-α add-on. DESIGN: 53 HBeAg-negative NUC-treated patients with CHB were randomised at a 1:1 ratio to receive pegIFN-α-2a for 48 weeks, or to continue NUC therapy and then followed up for at least 6 months maintaining NUCs. Serum hepatitis B surface antigen (HBsAg) and hepatitis B core-related antigen (HBcrAg) levels as well as peripheral blood NK cell phenotype and function and HBV-specific T cell responses upon in vitro stimulation with overlapping HBV peptides were measured longitudinally before, during and after pegIFN-α therapy. RESULTS: Two cohorts of pegIFN-α treated patients were identified according to HBsAg decline greater or less than 0.5 log at week 24 post-treatment. PegIFN-α add-on did not significantly improve HBV-specific T cell responses during therapy but elicited a significant multispecific and polyfunctional T cell improvement at week 24 post-pegIFN-α treatment compared with baseline. This improvement was maximal in patients who had a higher drop in serum HBsAg levels and a lower basal HBcrAg values. CONCLUSIONS: PegIFN-α treatment can induce greater functional T cell improvement and HBsAg decline in patients with lower baseline HBcrAg levels. Thus, HBcrAg may represent an easily and reliably applicable parameter to select patients who are more likely to achieve better response to pegIFN-α add-on to virally suppressed patients.

Effect of hepatitis B vaccination on HBV-infection among school children in Yaounde; ten years after the introduction of HBV vaccine into routine Immunization Program in Cameroon.

Introduction: since the introduction of the anti-HBV vaccine into the Expanded Program on Immunization (EPI) in 2005 in Cameroon, vaccination coverage has reached 99.0%. This coverage would indicate an increase in the number of children immune to Hepatitis B Virus (HBV) and a decrease in susceptibility to HBV-infection. This study was conducted to evaluate the effect of the HBV vaccine on pediatric HBV-infection in Yaounde, Cameroon. Methods: this school-based cross-sectional study was conducted from February to May 2016 among 180 children from Nkomo public school. The study population was stratified into two groups: vaccinated (n=95) versus (vs) unvaccinated (n=85). Screening for HBV biomarkers was done using a rapid panel test for detection (HBsAg, HBeAg and anti-HBc) and anti-HBs titer using enzyme linked immunosorbent assay (ELISA). Statistical analyses were done using SPSS v. 22 with p < 0.05 considered significant. Results: the mean age was 9.65 years. HBsAg (p=0.019) and anti-HBc (p=0.001) rates were detected in children aged ≥10 years and children aged < 10 years (95.95% [71/74]) were vaccinated vs 22.64% (24/106) for those aged ≥10 years (OR: 80.86; 95% CI: 23.36%-279.87%, p < 0.0001). According to anti-HBV vaccination status, HBsAg rate varied from [9.41% (8/85) to 1.05% (1/95), p=0.025], HBeAg rate varied from [2.35% (2/85) to 0% (0/95), p= 0.42] and anti-HBc rate ranged from [12.94% (11/85) to 2.10% (2/95), p= 0.011]. Conclusion: despite the variability of the anti-HBs titer, vaccination against HBV has a positive effect on the reduction of HBV-infection in children in tropical settings such as Cameroon.

Insights into the Natural and Treatment Courses of Hepatitis B in Children: A Retrospective Study.

Chronic Hepatitis B virus (HBV) infection in children remains a significant public health challenge. The natural history and treatment outcomes of HBV can vary widely, influencing management strategies. This retrospective study was conducted in Northeast Romania and involved a cohort of 148 pediatric patients diagnosed with chronic viral Hepatitis B. Of these, 59 children underwent antiviral treatment while 89 were not treated. One of the main objectives was the rate of HBeAg (Hepatitis B-e antigen) seroconversion, a marker of disease progression and response to therapy. Among the treated group, 26 children (44%) achieved HBeAg seroconversion following therapy. In contrast, 44 of the untreated children (49%) experienced spontaneous HBeAg seroconversion, indicating a substantial rate of natural resolution within this population subset. The findings highlight a significant proportion of spontaneous seroconversion in untreated pediatric patients, suggesting a potential re-evaluation of treatment criteria and timing for children with chronic HBV infection. The comparable rates of seroconversion between treated and untreated cohorts underscore the need for individualized treatment approaches based on a combination of virological, biochemical, and clinical parameters. Further studies are required to refine management strategies to optimize long-term outcomes in pediatric HBV infections.

Surface antigen serocleared hepatitis B virus infection increases the risk of mixed cryoglobulinemia vasculitis in male patients with chronic hepatitis C.

Mixed cryoglobulinemia vasculitis (MCV) is caused in ~90% of cases by chronic hepatitis C virus (HCVposMCV) and more rarely by hepatitis B virus (HBV) infection, or apparently noninfectious. HCVposMCV develops in only ~5% of patients with chronic hepatitis C (CHC), but risk factors other than female gender have not been identified so far. We conducted a retrospective case control study investigating whether past active HBV infection, defined by hepatitis B surface antigen (HBsAg) seroclearance and anti-core antibody (HBcAb) positivity, could be a risk factor for developing HCVposMCV. The prevalence of HBsAg seroclearance was 48% within 123 HCVposMCV patients and 29% within 257 CHC patients (p=0.0003). Multiple logistic regression including as variables gender, birth year, age at HBV testing, cirrhosis, and hepatocellular carcinoma, confirmed an association of HBsAg seroclearance with HCVposMCV [adjusted odds ratio (OR) 2.82, 95% confidence interval (95% CI) 1.73-4.59, p<0.0001]. Stratification by gender, however, showed that HBsAg seroclearance was associated with HCVposMCV in male [OR 4.63, 95% CI 2.27-9.48, p<0.0001] and not in female patients [OR 1.85, 95% 95% CI 0.94-3.66, p=0.076]. HBsAg seroclearance, and more likely occult HBV infection, is an independent risk factor for HCVposMCV in male CHC patients.

Production and Purification of Adeno-Associated Viral Vectors for the Development of Immune-Competent Mouse Models of Persistent Hepatitis B Virus Replication.

Mice infected with a recombinant adeno-associated virus carrying a replication-competent hepatitis B virus genome (rAAV-HBV) via the intravenous route establish a persistent HBV replication in hepatocytes and develop immune tolerance. They serve as models to evaluate antiviral immunity and to assess potential therapeutic approaches for chronic HBV infection. Combining selected HBV variants and different mouse genotypes allows for addressing a broad spectrum of research questions. This chapter describes the basic principles of the rAAV-HBV mouse model, rAAV-HBV production and purification methods, and finally, the in vivo application.

The prevalence of hepatitis B virus infection among HIV-infected patients in the Ningxia Hui Autonomous Region, China, November 2002 to July 2023.

We tested HIV-infected people with HBV serological markers of Ningxia. Of 1008 HIV-positive individuals, 70 (6.9 %) tested positive for HBsAg, 570 (56.5 %) tested positive for anti-HBs, and 483 (47.9 %) tested positive for anti-HBc. Of 70 HBV-positive individuals, 13 (18.5 %) tested positive for HBeAg, 31 (44.3 %) tested positive for anti-HBe, 3 (4.2 %) exhibited acute infection.

Investigating linkage to care following community-based screening for hepatitis B virus in rural Senegal: A mixed methods study.

This paper investigates linkage to care following community-based screening for hepatitis B virus (HBV) in rural Senegal. HBV-positive participants who completed a biological and clinical examination to assess liver disease and treatment eligibility were referred to a regional hospital (if eligible for treatment), invited to join the Sen-B research cohort study (adults with detectable viral load) or referred to their local health centre (all others). Logistic regressions were conducted to investigate factors associated with (i) uptake of the scheduled post-screening examination, and (ii) HBV management initiation. Obstacles to HBV management were identified using thematic analysis of in-depth patient interviews. Of the 206 HBV-positive participants, 163 (79.1%) underwent the examination; 47 of the 163 (28.8%) initiated HBV management. Women, people not migrating for >6 months/year, individuals living in households with more agricultural and monetary resources, with other HBV-positive participants, and beneficiaries of the national cash transfer program, were all more likely to undergo the examination. The likelihood of joining the Sen-B cohort increased with household monetary resources, but decreased with agricultural resources. Initiation of HBV management in local health centre was higher among participants with a non-agricultural economic activity. Individuals reported wariness and confusion about HBV management content and rationale at various stages of the care continuum, in particular with respect to venous blood sampling and management without treatment. In conclusion, HBV community-based test-and-treat strategies are feasible, but early loss to follow-up must be addressed through simplified, affordable management and community support and sensitization.

Hepatitis B Elimination Globally-The Answer May Not Be the Same for Everyone.

While progress has been made towards global elimination of hepatitis B virus, many countries lag behind. A one-size-fits-all approach is not practical to address HBV. Rather, the approach should be tailored to local prevalence, risk factors and available resources.

Exploration of 1-(indolin-1-yl)-2-(thiazol-2-yl)ethan-1-one derivatives as novel anti-HBV agent with potential TLR7-agonistic effect.

Hepatitis B virus (HBV) infection, as a serious global public health issue, is closely related to the immune dysfunction. Herein, thirty-seven 1-(indolin-1-yl)-2-(thiazol-4-yl)ethan-1-one derivatives were prepared as potential immunomodulatory anti-HBV agents. Anti-HBV activity evaluation confirmed compound 11a could significantly suppress the HBV DNA replication in both wild and resistant HBV stains, with IC50 values of 0.13 µM and 0.36 µM, respectively. Preliminary action mechanism studies showed that 11a had an inhibitory effect on cellular HBsAg secretion and could effectively activate TLR7, thereby inducing the secretion of TLR7-regulated cytokines IL-12, TNF-α and IFN-α in human PBMC cells. SPR analysis confirmed that 11a could bind to TLR7 protein with an affinity of 7.06 µM. MD simulation predicted that 11a could form tight interactions with residues in the binding pocket of TLR7. Physicochemical parameters perdition and pharmacokinetic analysis indicated that 11a displayed relatively favorable drug-like properties. Considering all the results, compound 11a might be a promising lead for developing novel immunomodulatory anti-HBV agents.

Risk Factors and Comorbidities Associated With Hepatocellular Carcinoma in Patients With Chronic Hepatitis B Virus Infection.

INTRODUCTION/OBJECTIVES: Chronic hepatitis B virus infection (CHBVI) is a major public health problem affecting about 296 million people worldwide. HBV infects the liver, and when it becomes chronic, may cause cirrhosis and hepatocellular carcinoma (HCC). The aim of our study was to identify the risk factors and comorbid medical conditions that were associated with HCC in patients who had CHBVI. METHODS: We performed a retrospective electronic medical record review of adult patients diagnosed with CHBVI, who presented to our primary care office between October 1, 2017 and October 21, 2022. Selected variables in patients with CHBVI with HCC (HCC group) were compared to those without HCC (NoHCC group). RESULTS: Among 125 patients with CHBVI, 24% had HCC and 76% did not have HCC. There were higher frequencies of association of certain comorbidities in the HCC group compared to NoHCC group, such as anemia (63.3% vs 26.3%; P < .001), ascites (53.3% vs 1.1%; P < .001), portal hypertension (43.3% vs 0.0%; P < .001), chronic kidney disease (40.0% vs 13.7%; P = .002), and HCV coinfection (13.3% vs 7.4%; P < .001). The logistic regression model showed increased odds of HCC for each year of increase in age (OR = 1.06, 95% CI = 1.01-1.11; P = .014), and increased odds in men (OR = 5.96, 95% CI = 1.71-20.73; P = .005). Although Asians represented the racial majority in both the groups, there was no significant difference in the race distribution between the two groups. CONCLUSION: In patients with CHBVI, increasing age and male sex are factors associated with increased odds of having HCC. Patients with CHBVI and HCC have higher frequencies of association of tobacco use, recreational drug use, anemia, ascites, portal hypertension, chronic kidney disease, and co-infection with HCV.

Hepatitis B virus infection during pregnancy and the risk of postpartum hemorrhage: a protocol for systematic review and meta-analysis.

Background: Hepatitis B virus (HBV) infection is a significant public health issue worldwide, with a hepatitis B surface antigen (HBsAg) seroprevalence of 3.5%. Maternal HBV infection during pregnancy, a common comorbidity, is associated with an increase in the risk of adverse obstetric and perinatal outcomes. However, the relationship between maternal HBV infection and postpartum hemorrhage (PPH), a leading contributor to maternal morbidity and mortality, is currently uncertain. The aim of this study is to comprehensively clarify the potential impact of maternal HBV on PPH risk. Methods and Analysis: The authors initially searched five English databases and three Chinese databases from their inception to 26th June 2023. Two reviewers will independently conduct study selection, data extraction, and quality assessment. Cohort and case-control studies investigating the effect of maternal HBV infection on PPH will be included, with study quality assessed using the Newcastle-Ottawa Scale (NOS). Meta-analyses will be performed using a fixed-effects model for I 2≤50% or a random-effects model otherwise. Several categories of subgroup analyses (e.g. sample size more than 1000 vs. less than 1000) and sensitivity analyses (e.g. omit NOS scores less than 7) will be conducted, and publication bias will be assessed through funnel plots, Begg's and Egger's tests using STATA 18.0. Ethics and Dissemination: This systematic review and meta-analysis do not require ethics approval and the results will be published in peer-reviewed journals. The findings of this systematic review will provide evidence on the impact of maternal HBV infection on PPH, which will contribute to better prevention and management of PPH in clinical practice and a better understanding of the disease burden of HBV infection. PROSPERO registration number: CRD42023442626.

Reactivation Risk of Latent Tuberculosis or Inactive Hepatitis B Virus Infection and Effectiveness of Ustekinumab in Chinese Plaque Psoriasis Patients: A 28-Week Retrospective, Observational Study.

Introduction: This study observed the effectiveness of ustekinumab and reactivation risk of concurrent latent tuberculosis infection (LTBI) and inactive hepatitis B virus (HBV) infection in Chinese mainland psoriasis patients on ustekinumab treatment. Methods: This retrospective, multicenter, observational study was conducted in three centers in China. Adult patients with moderate to severe plaque psoriasis were treated with ustekinumab for 28 weeks. The effectiveness endpoint included 75% and 90% improvement in Psoriasis Area Severity Index (PASI75/90) response rate, percentage of PASI improvement, change of absolute PASI score and body surface area involvement (BSA) score, absolute PASI ≤1/3 and Physicians' Global Assessment (PGA)=0/1, as well as Dermatology life quality index (DLQI)=0/1 response rate at week 4, 16 and 28. Screening of tuberculosis and hepatitis were performed at baseline and week 28. Results: A total of 82 patients were enrolled between March 2021 and May 2023 and the number of patients combined with LTBI and inactive HBV infection was 20 and 21 respectively. The PASI75 and PASI90 response rate at week 28 was 95.1% and 81.7% respectively. The mean PASI score decreased from 14.93 ± 12.07 at baseline to 0.78 ± 1.86 at week 28, and the mean BSA score decreased from 21% ± 18% at baseline to 1% ± 2% at week 28 (both P<0.001 compared with baseline). DLQI 0/1 response rate at week 28 was 73.2%. No reactivation of LTBI and inactive HBV infection and also no new-onset tuberculosis and hepatitis B occurred in patients without LTBI and inactive HBV infection at baseline. Conclusion: Ustekinumab demonstrated great effectiveness in Chinese plaque psoriasis patients and good safety in psoriasis concurrent with LTBI and inactive HBV infection under the real-world setting.

Implementation of Guideline-Based HBV Reactivation Management in Patients with Chronic HBV Infections of HBsAg or Resolved HBV Infection Undergoing Immunosuppressive Therapy.

INTRODUCTION: Although patients with HBV have a risk of reactivation after immunosuppressive therapy (IST), the status of their risk management is unclear in Japan. This study aims to describe the proportion of patients who received preventive management of HBV reactivation during ISTs in patients with chronic HBV infection of HBsAg or resolved HBV infection. METHOD: A retrospective cohort study was conducted using the JMDC Japanese claims database from April 2011 to June 2021. Patients with HBV infections of HbsAg who received ISTs or patients who had resolved HBV infections who received ISTs were identified from the database and evaluated for appropriate management to prevent HBV reactivation. RESULTS: In total, 6242 eligible patients were identified. The proportions of patients with appropriate HBV reactivation management, stratified by the HBV reactivation risk level of IST, was 43.1% (276/641) for high-risk, 40.2% (223/555) for intermediate-risk and 14.9% (741/4965) for low-risk patients. When the evaluation period for the outcome calculation was shortened from 360 to 180 days, the proportion for high risk increased to 52.7%. The odds ratios of large hospitals for receiving appropriate management were 2.16 (95% CI 1.12-4.44) in the high-risk, 4.63 (95% CI 2.34-10.25) in the intermediate-risk and 3.60 (95% CI 3.07-4.24) in the low-risk patients. CONCLUSION: HBV reactivation management was tailored according to the reactivation risk associated with IST. However, adherence to HBV reactivation management guidelines was sub-optimal, even among high-risk patients. This is especially the case for ensuring smaller-sized medical institutions, highlighting the need for further educational activities.

The study assesses the implementation of guideline-based management of hepatitis B virus reactivation during immunosuppressive therapy in Japan. The appropriate management of hepatitis B virus treatment involves prophylactic nucleos(t)ide analog (NUC) therapy and regular monitoring of hepatitis B virus DNA. This study aims to assess the extent to which these management practices are implemented in a clinical setting in Japan using a retrospective cohort study using the Japanese Medical Claims Database. The analysis identified 6242 eligible patients and identified whether they received appropriate management to prevent hepatitis B virus reactivation based on the level of risk associated with their immunosuppressive therapy. Based on the guidelines, the proportions of patients receiving appropriate reactivation management were 43.1% for high-risk, 40.2% for intermediate-risk and 14.9% for low-risk immunosuppressive therapy patients. Shortening the evaluation period from 360 to 180 days showed an increase in the proportion of high-risk patients to 52.7%, which indicated the potential challenge for continued monitoring after immunosuppressive therapy administration. The study shows that large hospitals present higher odds of patients receiving appropriate management. Overall, adherence to hepatitis B virus reactivation management guidelines was suboptimal, especially in smaller medical institutions, emphasizing the need for additional educational activities.

A Systematic Review of the Advances in the Study of T Lymphocyte Suppressor Receptors in HBV Infection: Potential Therapeutic Targets.

Background: HBV-specific T lymphocytes are pivotal in eliminating the hepatitis B virus (HBV) and regulating intrahepatic inflammatory reactions. Effective T cell responses curtail HBV infection; however, compromised immunity can result in persistent infection. Beyond the acute phase, the continued presence of antigens and inflammation leads to the increased expression of various inhibitory receptors, such as PD-1, CTLA-4, Tim-3, LAG3, 2B4, CD160, BTLA, and TIGIT. This escalates the dysfunction of and diminishes the immune and proliferative abilities of T cells. Methods: In this study, we reviewed English-language literature from PubMed, Web of Science, and Scopus up to 9 July 2023. This paper aims to elucidate the inhibitory effects of these receptors on HBV-specific T lymphocytes and how immune function can be rejuvenated by obstructing the inhibitory receptor signaling pathway in chronic HBV patients. We also summarize the latest insights into related anti-HBV immunotherapy. Result: From 66 reviewed reports, we deduced that immunotherapy targeting inhibitory receptors on T cells is a reliable method to rejuvenate T cell immune responses in chronic HBV patients. However, comprehensive combination therapy strategies are essential for a functional cure. Conclusions: Targeting T cell suppressor receptors and combining immunotherapy with antiviral treatments may offer a promising approach towards achieving a functional cure, urging future research to prioritize effective combination therapeutic strategies for chronic HBV infection.

Effect of S-region mutations on HBsAg in HBsAg-negative HBV-infected patients.

BACKGROUND: Occult HBV infection (OBI) is a special form of hepatitis B virus (HBV) infection that may cause Liver cirrhosis and hepatocellular carcinoma, causing significant harm to patients. Given the insidious nature of OBI, it is usually not easy to be detected. Most of the samples currently studied are concentrated on blood donors, however, patients in this special state have not been fully studied. This project aimed to study the effect of HBV S region mutations on HBsAg in patients with clinical OBI. METHODS: Collect 107 HBsAg-/HBV DNA + blood samples from Beijing Youan Hospital, Capital Medical University from August 2022 to April 2023. Next, the successfully extracted and amplified HBV DNA S regions were sequenced. Construct mutant plasmids to verify the cell function of the high-frequency mutation sites and explore the possible molecular mechanism. RESULTS: Sixty-eight HBsAg-negative samples were sequenced, revealing high-frequency amino acid substitution sites in the HBV S protein, including immune escape mutations (i.e., sY100C、sK122R、sI126T、sT131P、and sS114T) and TMD (Transmembrane domain) region substitutions (i.e., sT5A、sG10D、sF20S、and sS3N). We constructed a portion of the mutant plasmids and found that sT5A, sF20S, sG10D, sS3N, sI68T, and sI126T single point mutations or combined mutations may decrease HBsAg expression or change the antigenicity of HBsAg leading to detection failure. CONCLUSIONS: HBsAg-negative patients may show various mutations and amino acid replacement sites at high frequency in the HBV S-region, and these mutations may lead to undetectable Hepatitis B surface antigen (HBsAg), HBsAg antigenic changes or secretion inhibition.

Diagnostic precision of Truenat® technique and co-relation of ALT levels with HBV-DNA viral load among HBsAg positive patients at a tertiary care hospital in Eastern Uttar Pradesh.

Background and Objectives: In India, it is estimated that there are 40 million people suffering from Hepatitis B virus (HBV). Quantification of the viral burden is an important laboratory tool in the management. However, widespread use of different HBV-DNA assays is still affected by the high cost and variable diagnostic precision. The present study was conducted to evaluate the diagnostic precision and co-relation of ALT levels with HBV-DNA by Truenat®-PCR. Materials and Methods: In this prospective cross-sectional study a total of 567 serums were collected from patients by rapid HBsAg, and processed for liver function tests (LFT). The viral HBV-DNA amplification detection was carried out through by Truenat®-PCR test. Results: Out of 567 samples, 452 samples were found to be positive by both rapid and Truenat®-PCR and 106 were negative for HBV-DNA followed by 9 invalid. High ALT level found in 73% of positive patients who had HBV-DNA level (>100000 copies/ml) which is significantly higher in 447 patients as compared to those have below ≤100000 copies/ml. Conclusion: Truenat®-PCR technique is a highly sensitive and can be performed with low resources for effective control of HBV infection. Evaluation of HBV-DNA levels and serum ALT levels showed a significant proportion of patient harbored ongoing viral replication and disease progression.