HBsAg Titer Research Articles

Evaluation of the Relationship of HBsAg Serum Plasma Values with HBV DNA and Other Serologic Markers in the Diagnosis of Hepatitis B

Objective: Hepatitis B virus (HBV) infections cause a major public health problem worldwide diagnosis and treatment of HBV infection is an important issue. Detection of HBV DNA by polymerase chain reaction (PCR) and demonstration of viral replication together with serologic and biochemical indicators are very useful in diagnosis and treatment. In this study, we aimed to evaluate the relationship between HBsAg serum concentration values and other serologic parameters related to HBV in the diagnosis of hepatitis B. Methods: HBsAg, HBV DNA, Anti HBc IgG, Anti HBc IgM, HBeAg, and Anti HBe values obtained from blood sera taken from patients in Sivas Cumhuriyet University Application and Research Hospital Microbiology Laboratory between 2012-2020 were retrospectively analyzed from laboratory records. Results: A positive correlation was found between HBsAg serum titers and HBV DNA and between HBeAg and HBV DNA. It was found that HBV DNA positivity rates increased as HBsAg titers increased. Similarly, it was found that HBc IgG positivity increased as HBsAg titers increased. HBeAg positivity increased with increasing HBsAg titers up to a certain point, while HBeAg positivity decreased after a certain titer. When HBV DNA results were compared with HBeAg results, the relationship between the two values was found to be significant. Conclusion: We think that it is useful to investigate the relationship between serum concentrations of HBsAg and HBV DNA and other serologic parameters in the accurate identification of HBV infection and monitoring of treatment.

Predictors of Functional Cure of Chronic Hepatitis B Virus Infection: A Long-Term Follow-Up Study

Functional cure is an essential endpoint in the management of patients with chronic hepatitis B virus (HBV) infection. We evaluated the cumulative probability and predictors of functional cure in patients with chronic HBV infection after hepatitis B e antigen (HBeAg)-seroconversion. We retrospectively analyzed 413 (249 males and 164 females) initially HBeAg-positive chronic HBV-infected patients, who were followed up for a mean of 26.36 ± 0.53 years. All underwent HBeAg-seroconversion during follow-up. A functional cure was defined as durable HBsAg and HBV DNA loss without antiviral treatment for more than 24 weeks. After 10,888 person-years of follow-up, the cumulative probability of functional cure was 14.53% (n = 60). There were 24 (40%) subjects with functional cure after antiviral therapy. The annual functional cure rate was 0.55% per perperson-year, and increased to 0.96% per person-year after HBeAg-seroconversion. In subjects with functional cure, the HBsAg and HBV DNA titers after HBeAg-seroconversion were positively correlated with the time to functional cure (P < .001 and < .001, respectively). Multivariate Cox proportional hazard analysis of the cohort revealed that HBeAg-seroconversion at < 18 years of age, high genetic barrier nucleos(t)ide analogue(s) therapy before HBeAg-seroconversion, and a serum HBsAg titer < 1,000 IU/mL at 18 months after HBeAg-seroconversion were significant predictors of functional cure (P < .001, .001, and .001, respectively). In a cohort of chronic HBV-infected patients with long-term follow-up, HBeAg-seroconversion in childhood, high genetic barrier nucleos(t)ide analogue(s) therapy, and low HBsAg titers after HBeAg-seroconversion were significant predictors of functional cure.

Evaluating the Status of Hepatitis B Vaccination in Healthcare Workers at a Central Laboratory in a Tertiary Care Hospital and Research Centre.

Introduction Hepatitis B virusis a significant occupational hazard for healthcare workers worldwide. Long-term protection against hepatitis B infection is conferred by the vaccineand the protective immune response is indicated by anti-hepatitis B surface antigen (HBsAg) titre. It is crucial to monitor anti-HBsAg titres as their levels decrease over time. The study aims to evaluate thestatus of hepatitis B vaccination among personnel working in the Central Laboratory of Shri B.M. Patil Medical College Hospital and Research Centre. The focus is on understanding the immunization practices and protection levels against HBV within this high-risk group. Materials and methods A cross-sectional analysis was conducted, including collecting demographic data, determining HBsAgstatus, evaluating anti-HBsAg titre value, and getting vaccination details of the laboratory personnel. The study participants included doctors, lab technicians, and attendants who were assessed for both vaccination coverage and immunity levels. After obtaining their written consent, 4 ml of blood was collected in sterile blood collection tubes. All the samples were tested for HBsAg. The negative samples were tested for anti-hepatitis B surface antigen antibody (HBsAg-Ab (IgG)) titre. The enzyme-linked immunosorbent assay (ELISA) method was used to evaluate the obtained samples for HBsAg and anti-HBsAg titre. Results A total of 99 healthcare workerswere included in the study. Most of the laboratory healthcare workers were in the age range of 20-30 years.In 84.8% of the subjects, protective antibody levels (>10 IU/ml) were found. The highest protection was seen among doctors (94.5%), followed by lab technicians (82.9%) and attendants (66.6%). However, 15.2% exhibited inadequate immunity, predominantly among the attendants (33.3%). The highest vaccination coverage was among doctors (91.8%), followed by lab technicians (78.7%) and attendants (53.3%). Most doctors had completed the full vaccination schedule (70.2%) or received a booster dose (24.3%) compared to lab technicians (57.4%)and attendants (46.6%). Conclusion The study highlights effective preventive measures against HBV among laboratory healthcare workers, as indicated by the absence of active infections. But it also emphasizes the necessity of focused initiatives to raise vaccination rates, particularly among attendants, in order to guarantee complete protection against HBV for all levels of laboratory workers.

Assessment of hepatitis B virus relapse in cancer patients receiving chemotherapy with prophylactic nucleos(t)ide analogues: Implications for overall mortality.

We aimed to explore the risk factors associated with virological and clinical relapse, as well as their impact on overall mortality, in hepatitis B virus (HBV)-infected patients receiving nucleos(t)ide analogues (NUCs) therapy prior to chemotherapy initiation. From 2010 to 2020, we conducted a prospective cohort study involving patients with HBV infection undergoing cytotoxic chemotherapy. We utilized the Kaplan-Meier method and Cox proportional hazard regression models to assess risk factors. We observed that TDF or TAF (HR: 2.16, 95% CI 1.06-4.41; p = .034), anthracycline (HR: 1.73, 95% CI 1.10-2.73; p = .018), baseline HBV DNA (HR: 1.55, 95% CI 1.33-1.81; p < .001) and end-of-treatment HBsAg titre >100 IU/mL (HR: 7.81, 95% CI 1.94-31.51; p = .004) were associated with increased risk of virological relapse. Additionally, TDF or TAF (HR: 4.91, 95% CI 1.45-16.64; p = .011), baseline HBV DNA (HR: 1.48, 95% CI 1.10-1.99; p = .009) and end-of-treatment HBsAg titre >100 IU/mL (HR: 6.09, 95% CI .95-38.87; p = .056) were associated with increased risk of clinical relapse. Furthermore, we found that virological relapse (HR: 3.32, 95% CI 1.33-8.32; p = .010) and clinical relapse (HR: 3.59, 95% CI 1.47-8.80; p = .005) significantly correlated with all-cause mortality in HBV patients receiving cytotoxic chemotherapy with prophylactic NUCs therapy. The risk of virological and clinical relapse was linked to baseline HBV DNA, end-of-treatment HBsAg levels and TDF or TAF for prophylaxis; additionally, experiencing relapse heightens the risk of all-cause mortality. Further research is warranted to explore potential strategies for preventing virological and clinical relapse in high-risk patients.

Plasma Adiponectin Levels in Relation to Chronic Hepatitis B Infection Progression to Liver Cancer Milestones: A Prospective Study

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Our previous nested-case-control study demonstrated elevated adiponectin increased liver cirrhosis and HCC risk in HBV carriers. We extended the analysis to the whole REVEAL-HBV cohort to prospectively evaluate whether adiponectin directly affected end-stage liver diseases, or through affecting HBV progression. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Baseline plasma adiponectin was determined to investigate the association between adiponectin and subsequent HBeAg, HBsAg, and HBV DNA seroclearance, and the development of cirrhosis, HCC and liver-related death. Whether HBV characteristics modify the adiponectin-milestones associations was also examined. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Among 3,931 HBsAg(+)/anti-HCV(−) REVEAL-HBV participants, 3,684 had sufficient biosamples left for adiponectin assay. Elevated adiponectin was associated with a higher chance of HBeAg-seropositive, high HBV viral load (≥2 × 10&lt;sup&gt;5&lt;/sup&gt; IU/mL) and high HBsAg titers (≥1,000 IU/mL) in a dose-response manner (OR = 2.25, 95% CI: 1.55–3.28; OR = 2.11, 95% CI: 1.47–3.04; and OR = 1.92, 95% CI: 1.47–2.52 for Q5 vs. Q1, respectively). Those with the highest quintile had a lower chance of achieving HBeAg (HR = 0.48, 95% CI: 0.27–0.85), HBsAg (HR = 0.69, 95% CI: 0.49–0.97), and HBV DNA seroclearance (HR = 0.63, 95% CI: 0.43–0.90) and a higher chance of developing liver cirrhosis (HR = 2.88, 95% CI: 1.98–4.20, HCC (HR = 2.38, 95% CI: 1.52–3.73), and died from liver-related causes (HR = 2.32, 95% CI: 1.51–3.54). HBV genotype significantly modified the adiponectin-HCC (P&lt;sub&gt;interaction&lt;/sub&gt; = 0.005) and adiponectin-liver death associations (P&lt;sub&gt;interaction&lt;/sub&gt; = 0.0157), with higher risk among genotype C. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; Elevated adiponectin is consistently associated with all important chronic HBV infection milestones toward progression to liver cancer. The exact mechanism of how adiponectin mediates HBV infection toward carcinogenesis remains unclear and warrants further investigation. Disentangling this may help us in finding new HBV treatment target, biomarker in HBV surveillance to identify high-risk patients, or even cancer prevention.

Modulation of monocyte activity by hepatocellular MicroRNA delivery through HBsAg particles: Implications for pathobiology of chronic hepatitis B.

HBsAg serves as an important immune-modulatory factor in chronic hepatitis B. One aspect of such modulation may act through monocytes, which are the major Ag-presenting cells taking up HBsAg. There is evidence for the encapsulation of hepatocellular microRNAs (miRNAs) by HBsAg particles, while its pathobiological significance is unclear. Here, we characterized the miRNA profile in patients with chronic hepatitis B and probed their association with liver inflammation. We collected plasma from patients that are treatment-naive with chronic hepatitis B (n = 110) and quantified total/HBsAg-enveloped miRNAs by qRT-PCR and plasma cytokines by ELISA. The biological effects of HBsAg-delivered miRNAs in monocytes were evaluated using multiple approaches. The clinical significance of candidate miRNAs and cytokines was corroborated in patients with HBV-associated advanced liver diseases. The plasma miRNA profile showed 2 major clusters, one significantly associated with HBsAg titer and the other correlated with liver inflammation. Among HBsAg-carried miRNAs, miR-939 displayed the most significant correlation with IL-8. Mechanistically, miR-939 in subviral particles enters monocytes and significantly augments IL-8 production through the mitogen-activated protein kinase (MAPK) p38 signaling pathway. Finally, the findings that miR-939 positively correlated with IL-8 level and inflammation/fibrosis stage in the cohort of HBV-associated advanced liver diseases support its causative role in the progression of liver diseases. HBsAg particles carry hepatocellular miRNAs, including miR-939, which enter monocytes and alter their functional status, such as IL-8 secretion. Our findings demonstrate that the HBsAg-miR-939-IL-8 axis may play a crucial role in HBV-induced hepatic necro-inflammation and the progression of advanced liver diseases.

Correlation between quantitative HBsAg and quantitative HBV DNA in chronic hepatitis B patients: a systematic review and meta-analysis

BackgroundHBV DNA assays have several limitations including being expensive and not widely available. Detection of HBsAg in serum has been the hallmark of HBV infection. However, previous studies regarding the association between HBsAg and HBV DNA revealed contradictory results. This study aims to reassess the correlation between HBsAg and HBV DNA in chronic hepatitis B patients.MethodsObservational studies with näive chronic hepatitis B patients were included, while studies with other coinfections were excluded. The studies were identified by searching through Google Scholar, PubMed, ScienceDirect, and Springer Link for English and Bahasa articles from 2011 to 2021. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) was followed. Study quality was assessed using the Joanna Briggs Institute (JBI) critical appraisal.ResultsA total of 17 studies with 4134 participants met the criteria. The overall analysis revealed a moderate correlation between quantitative HBsAg and quantitative HBV DNA in the total sample of chronic hepatitis B patients (r = 0.57, 95% CI 0.40–0.75, P < 0.00001). In HBeAg + group, a moderate correlation was indicated while in HBeAg − revealed a weak association (r = 0.55, 95% CI 0.39–0.70, P < 0.00001 vs r = 0.29, 95% CI 0.20–0.38, P < 0.00001). The strongest correlation was discovered in HBeAg + chronic HBV infection phase (r = 0.59, 95% CI 0.35–0.82, P < 0.00001).ConclusionSerum HBsAg titer supports as a predictor of serum HBV DNA levels in clinical practice with moderate strength of correlation.Trial registrationThis review had been registered in PROSPERO (ID: CRD42023421246).

Factors Positively Correlated with Hepatitis B Surface Antigen Seroconversion in Chronic Hepatitis B.

Chronic hepatitis B virus (HBV) infection is a global public health challenge since more than 250 million individuals are affected worldwide. Since different treatment modalities are available and not all patients are candidates for antiviral treatment, biomarkers that potentially predict the possibility of HBsAg clearance and seroconversion may be useful in clinical practice. In this retrospective study, we aimed to identify factors positively correlated with HBsAg seroconversion in a large cohort of 371 chronic hepatitis B patients treated at a German tertial center between 2005 and 2020. Seroconversion occurred in 25/371 (6.7%) and HBsAg loss in 29/371 patients (7.8%) with chronic HBV infection. Antiviral therapy was associated with a lower chance of seroconversion (seroconversion antiviral therapy 14/260 (5.4%) vs. therapy-naïve patients 11/111 (9.9%), p = 0.027). Seroconversion rates were higher in patients with (very) low titers of HBV DNA (best cut-off value 357 IU/mL) and quantitative HBsAg. The best cut-off value with regard to seroconversion was 357 IU/mL for HBV DNA (AUC 0.693 (95%-CI 0.063-0.422), sensitivity 0.714, specificity 0.729; p < 0.0005) and 33,55 IU/mL for HBsAg (AUC 0.794 (95%-CI 0.651-0.937), sensitivity 0.714, specificity 0.949; p < 0.0005). However, male gender was positively associated with seroconversion (seroconversion: males 7.6% vs. females 2.7%, p = 0.036). Treatment-naïve male chronic HBV patients with low viral load and inflammatory activity have the best chance to achieve seroconversion. In the absence of cirrhosis, antiviral therapy should therefore not be performed in this patient collective.

Longterm Outcome of Therapeutic Vaccination with a Third Generation Pre-S/S HBV Vaccine (PreHevbrioR) of Chronically HBV Infected Patients.

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 PreHevbrioR. 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.

Long-Term HBsAg Titer Kinetics with Entecavir/Tenofovir: Implications for Predicting Functional Cure and Low Levels.

The long-term kinetics of quantitative HBsAg levels in HBV-infected patients treated with entecavir or tenofovir, as well as the role of quantitative HBsAg in predicting functional cure (HBsAg loss) and low HBsAg levels (<2 log IU/mL) remain unclear. Of some 1661 consecutively enrolled patients newly treated with entecavir or tenofovir, we analyzed 852 patients who underwent serial HBsAg level checks every 6-12 months. The primary outcomes included long-term kinetics in HBsAg levels and the rate of functional cure and achieving low HBsAg levels. Over a mean 6.3-year follow-up, the functional cure rate was 2.28% (n = 19), and 12.9% (n = 108) achieved low HBsAg levels. A significant HBsAg level reduction was seen in the first treatment year (p < 0.05), with another stepwise decrease between year 6-7. These trends were pronounced in patients with chronic hepatitis and HBeAg-positivity compared to those with cirrhosis and HBeAg-negativity, respectively. Baseline HBsAg of ≤3 log IU/mL and the first-year HBsAg reduction were key predictors for both functional cure and low HBsAg levels (p < 0.05). In conclusion, our findings elucidate the stepwise reduction in quantitative HBsAg dynamics during high-potency NA therapy (entecavir or tenofovir) along with variations based on different conditions. We also underscore the significance of quantitative HBsAg titer in predicting functional cure and low-HBsAg levels.

Clinical Value of Hepatitis B Virus RNA Detection in Patients with Chronic Hepatitis B Infection

Objective: To study the clinical value of hepatitis B virus pregenomic RNA (HBV-pgRNA) detection in the treatment of hepatitis B. Methods: 60 patients with hepatitis B were included in the study. Serum HBV-pgRNA and HBV DNA levels in different phases of infection and during treatment were detected, and serum hepatitis B surface antigen (HbsAg) titer was detected by chemiluminescent immunoassay. DNA was extracted from liver biopsy tissue, and covalently closed circular DNA was detected to predict the therapeutic value in patients. Results: At the initial stage of treatment, the level of HBV-pgRNA in phase I, II, III, and IV showed a gradual decrease. Comparing the levels of HBV-pgRNA before and after treatment, we found that the level of HBV-pgRNA was significantly lower after treatment (P &lt; 0.05). Among the indicators for predicting HBsAg seroconversion, the accuracy of HBV-pgRNA level was 85.0% (51/60). Conclusion: The clinical value of HBV-pgRNA detection in the treatment of hepatitis B is high.

FRI-268 - COVID-19 vaccination alters NK cell dynamics and transiently reduces HBsAg titers among patients with chronic hepatitis B

FRI-268 - COVID-19 vaccination alters NK cell dynamics and transiently reduces HBsAg titers among patients with chronic hepatitis B

Performance evaluation of in vitro diagnostic kits for hepatitis B virus infection using the regional reference panel of Japan

BackgroundHepatitis B virus (HBV) infection is a global public health concern. Precise and sensitive detection of viral markers, including HBV DNA and HBs antigen (Ag), is essential to determine HBV infection.MethodsThe sensitivities and specificities of 5 HBV DNA and 14 HBsAg kits were evaluated using World Health Organization International Standards (WHO IS) and the Regional Reference Panel (RRP) consisting of 64 HBsAg-negative and 80 HBsAg-positive specimens.ResultsAll 5 HBV DNA kits detected HBV DNA in the WHO IS at a concentration of 10 IU/mL. The sensitivity and specificity to the RRP were 98.8–100% and 96.9–100%, respectively. HBV DNA titers were well correlated among the 5 kits regardless of HBV genotype. However, discordance of the HBV DNA titer was found in 5 specimens measured by CAP/CTM HBV v2.0. Among 12 automated HBsAg kits, the minimum detectable concentrations in the WHO IS varied from 0.01 to 0.1 IU/mL. Two lateral flow assays were positive for WHO IS concentrations greater than or equal to 1.0 and 0.1 IU/mL, respectively. When analyzed by the RRP, 12 automated kits exhibited a sensitivity of 98.8–100%, and 2 lateral flow assays showed sensitivities of 93.8% and 100%. The specificities of HBsAg kits were 100%. In the quantification of HBsAg, some kits showed a poor correlation of measurements with each other and showed up to a 1.7-fold difference in the regression coefficient of HBsAg titers. There were variations in the correlations of measurements among HBsAg kits when analyzed by genotype.ConclusionsFive HBV DNA kits showed sufficient sensitivity and specificity to determine HBV infection. HBV DNA titers were compatible with each other irrespective of HBV genotypes. HBsAg kits had enough sensitivity and specificity to screen for HBV infection. One of the lateral flow assays had a nearly equivalent sensitivity to that of the automated HBsAg kit. HBsAg titers quantified by the evaluated kits were not compatible across the kits. Genotype-dependent amino acid variations might affect the quantification of HBsAg titers.

The Coexistence of Hepatitis B Surface Antigen and Anti-HBs in Patients With Chronic HBV Infection: Prevalence and Related Factors.

The prevalence of coexistence of HBsAg and anti-HBs in chronic hepatitis B virus (HBV)-infected patients is different between studies. The mutations on the S gene were proved as the cause of this coexistence. This study determined the frequency and factors associated with coexistence of HBsAg and anti-HBs in chronic HBV-infected patients. This cross-sectional study was conducted at University Medical Center at Ho Chi Minh City, Vietnam, from April 2014 to December 2020. HBeAg, HBsAg, and anti-HBs were measured by chemiluminescent immunoassay. Mutations on the HBV small S gene from amino acids 1-227 were detected using Sanger sequencing on 177 patients. A total of 521 chronic HBV-infected patients were enrolled, including 350 males (62.7%), 17.1% with hepatic fibrosis of ≥ F3 and 9.8% with hepatocellular carcinoma (HCC). The coexistence of HBsAg and anti-HBs was detected in 9.8%, with 17.9% among genotype C compared to 7.4% in genotype B, P= .001. The coexistence group had lower levels of HBsAg titers (P= .052). There were significantly higher rates of coexistence in the group with HCC (19.6% vs 8.7%, P= .013). The existence of point mutations on the major hydrophilic region and the "a" determinant region of HBV was more frequently detected in the HBsAg and anti-HBs coexistence group (P= .043 and P= .008, respectively). The coexistence of HBsAg and anti-HBs was detected more frequently in the HBV genotype C group. The coexistence status was related to lower HBsAg titers, mutations on the major hydrophilic region, and/or the "a" determinant and exposed significant relation with HCC.

Hepatitis B virus haplotype number at baseline is a predictive marker of functional cure during antiviral therapy for patients with genotypes A and D HBeAg-positive chronic hepatitis B.

We investigated associations between hepatitis B virus (HBV) genome-length haplotype number (HN) at baseline in subjects with HBeAg-positive chronic hepatitis B (CHB), and the likelihood of achieving functional cure during direct-acting antiviral therapy METHOD: We analysed 86 HBeAg-positive baseline samples from patients with HBV genotypes A and D who were enrolled in a Phase II trial of tenofovir disoproxil fumarate (TDF) to determine if HN was a biomarker of HBsAg loss during therapy. Findings were validated using baseline samples from 181 patients with HBV genotypes A and D from an independent clinical trial utilising TDF or tenofovir alafenamide therapy in HBeAg-positive CHB. In the HBeAg-positive test cohort, patients with genotypes A or D and ≤2 haplotypes had a minimum of 21-fold higher likelihood of achieving HBsAg loss on TDF. Baseline HN (p < 0.0001) was a stronger predictor of HBsAg loss on therapy than HBsAg titre (p=0.03), HBeAg titre (p=0.0002), or the presence of HBV basal core promoter (A1762T, p=0.0379 and G1764A, p=0.0176) or G1896A precore mutations (p= 0.0218). This finding was validated in the independent validation cohort. HN was statistically higher in patients with HBV genotypes B or C infection compared to genotypes A and D. Baseline HN ≤2 predicts which patients with HBV genotypes A or D will more likely progress to functional cure on current direct-acting antiviral therapy, with greater accuracy than current biomarkers including baseline HBsAg and HBeAg titre.

Effectiveness of prophylaxis for hepatitis B in infants born to mothers serologically positive in Benghazi Medical center

Background: The seroprevalence of HBs Ag among the general population in Libya was found to be 2.2 %. Libya is therefore considered an area of intermediate endemicity for hepatitis B. vertical transmission is considered as the main route of spread of this infection. Trans placental (intra-uterine) transmission is presumed to cause the minority. Risk factors for transmission of HBV include maternal HBe Ag positivity, HBs Ag titer, and HBV viral load. Active immunization with hepatitis B vaccine (Hep. B vaccine), and hepatitis B immunoglobulin (HBIG) is 85-95% effective in preventing the disease. The objective of the study: To assess the effectiveness of hepatitis B vaccine and hepatitis B immunoglobulin in the prevention of the Hep. B. virus transmission and to study the factors that affected the immune response of the newborn babies of mothers with hepatitis B positive infection during pregnancy. Patients &amp; Methods: A longitudinal cross-section study included 40 babies born to mothers with hepatitis B during the period from 1.1.2017 To 1.3.2019 at Benghazi Medical Center. The newborn babies have been immunized with Hepatitis BIG and Hepatitis B vaccine at birth, and further 3 doses of hep. B vaccine and HBIG. Multivariable analyses were done to assess the statistical significance associated with responders and nonresponders to HB immune prophylaxis. Results: all babies were negative for hepatitis Bs Ag in 40(100%), 35 (88%) their viral load was 10 mlIU/ml) in More than two-thirds (60%) and (63%) of infants at 9 months and 12 months respectively. Birth weight &gt;2.5 kg was significantly associated with immune response &gt;10 mIU/ml, whereas, Maternal viral load, time of administration of HBIG, and hep. B vaccine, gestational age, mode of delivery, type of feeding were statistically not significant. Conclusion: the study reported that all the newborn babies were negative for hepatitis B sAg after delivery, more than two-thirds of the babies were responders to immune-prophylaxis, and birth weight of &gt;2.5kg was significantly related to high immune-response.

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

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. 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. 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: 128.8IU/ml) were much higher than non-vaccinated infected blood donors (58.4IU/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. 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.

Association of Toll-Like Receptor 2 (TLR2) Expression in Placenta and Intrauterine Exposure to Hepatitis B Virus.

Introduction The placenta is a specialized organ that only performs during pregnancy and serves as an immunological barrier in preventing pathogens to reach the fetus. It has been known that toll-like receptors (TLRs) on the placenta respond to antigens, such as zymosan, lipopolysaccharide, and other viral infections. This study analyzes the distribution of TLR2 protein and hepatitis B DNA virus (HBV DNA) virus identification to gain an understanding of hepatitis B viral transmission from the mother to child. Methods We performed enzyme-linked immunoadsorbent assay of HBeAg, HBsAg titer, Anti-HBs, and Anti-HBc to 59 HBsAg-positive pregnant women and identified HBV DNA using nested PCR in their cord blood during delivery for evidence of exposure to HBV DNA. The expression of TLR2 protein in the placenta was performed using immunohistochemistry analysis. Results Intrauterine exposure to the hepatitis B virus occurred in 69.5% of all pregnant women who were HbsAg positive. TLR2 expression was predominantly identified in syncytiotrophoblast and cytotrophoblast cells with the highest score in mothers aged 20–35 years (75%), multigravida (58.3%), and mothers with term pregnancies (70.8%). Statistical analysis results showed that placental TLR2 expression did not indicate any association with hepatitis B virus DNA identified in cord blood with a p value of 0.730 and an OR of 0.650 (95% CI 0.173–2.440). Conclusion TLR2 expression is not associated with intrauterine exposure of hepatitis B virus.

Standardized Hepatitis B Virus RNA Quantification in Untreated and Treated Chronic Patients: a Promising Marker of Infection Follow-Up.

ABSTRACTThe measurement and interpretation of HBV DNA and RNA levels in HBV infected patients treated with antiviral therapy supports the objective of HBV disease management. Here, we quantified circulating HBV RNA through a standardized and sensitive assay in follow-up samples from both naive and treated patients as a marker of infection evolution. HBV DNA (HBV DNA for use in Cobas 6800/8800 Automated Roche Molecular Systems), RNA (Roche HBV RNA Investigational Assay for use in the Cobas 6800/8800; Roche), HBeAg and HBsAg (Elycsys HBsAg chemiluminescence immunoassay by Cobas 8000; Roche), and core-related antigen (Lumipulse G chemiluminescence assay; Fujirebio) levels were measured in cohorts of untreated or nucleos(t)ide treated, HBV-infected subjects in an outpatient hospital setting. HBV DNA levels in untreated people were 3.6 log10 higher than corresponding RNA levels and were stable over 5 years of observation. While only five of 52 treated patients had DNA levels below the lower limit of quantification (10 IU/mL) at the end of follow-up, 13 had HBV RNA levels persistently above this limit, including eight with undetectable DNA. In samples with undetectable core-related antigen we observed a median HBsAg titer 2.7-fold higher than in samples with undetectable RNA (adjusted P = 0.012). Detectable HBV RNA with undetectable HBV DNA was a negative predictor of HBsAg decrease to a level ≤100 IU/mL (P = 0.03). In naive patients the difference between HBV DNA and RNA was higher than previously reported. HBV RNA rapidly decreased during treatment. However, in some cases, it was detectable even after years of effective therapy, being a negative predictor of HBsAg decrease. The investigational RNA assay for use on the Cobas 6800/8800 instruments is a sensitive and standardized method that could be applied in general management of HBV infection.IMPORTANCE This study focused on the quantification of circulating HBV RNA by using a standardized and sensitive assay. Thanks to this system we observed a higher difference between circulating HBV DNA and RNA than previously reported. In treated patients, HBV RNA decreased together with DNA, although some patients presented detectable levels even after years of successful antiviral treatment, suggesting a persistent viral transcription. Of note, the detection of viral RNA when HBV DNA is undetectable was a negative predictor of HBsAg decrease to a level ≤100 IU/mL. This assay could be extremely helpful in HBV patients management to study viral transcription and to identify those treated patients that may achieve sustained viral suppression.

Spontaneous Seroclearance Is Associated with Lower Liver Fibrosis in Treatment-Naïve Chronic Hepatitis B Patients.

Chronic hepatitis B virus (HBV) is amajor publichealthconcern. Transient elastrography (TE) is a reliable method in assessing hepatic fibrosis in patients with liver disease. We assess the potential clinical associations between HBsAg seroclearance and the severity of liver fibrosis. We retrospectively performed a matched analysis of 23 consecutive HBsAg seroclearance patients who underwent TE between March 2008 and August 2021 from a community practice at a 1:3 ratio based on clinic visit date. Baseline laboratory and clinical data were collected. Fisher's exact test and Chi-square test for proportions, and Wilcoxon rank-sum test for median were performed. Twenty-three cases and 69 controls were identified.Median follow up (interquartile range) for the cases and controls was 24,314 (1402) and 2332 (1587) days (p = 0.15), respectively. All patients were Asian. Median age of cases was higher than controls (64 vs 52, p < 0.01, respectively). While most comorbidities were similar, diabetes and hyperlipidemia were more prevalent in cases. Baseline HBV DNA was detectable in 78% of cases and 97% of controls (p < 0.01).More cases had baseline HBsAg titers below 1000IU/mL than controls (81% vs 8.7%, p < 0.01). Other baseline laboratory values were similar. Few cases had a fibrosis score greater than 1, while control had over a quarter of patients with a fibrosis score of 2 or 3. Spontaneous HBsAg seroclearance remains rare in patients with chronic HBV infection. It is associated with low baseline HBsAg, and lower level of liver fibrosis as detected by TE.