Higher Hepatitis B Surface Antigen Research Articles

Correlates of Hepatitis B infection in pregnant women attending antenatal clinics in Wa Municipality, Ghana.

Despite the availability of an effective vaccine against viral hepatitis B infection, it remains prevalent, highly transmissible especially through mother-to-child, life-threatening, and a major public health challenge. A positive Hepatitis B e-Antigen (HBeAg) mother has a 90% risk of transmitting the virus to the unborn child in the perinatal period. This study sought to determine the prevalence and risk of Hepatitis B infection among pregnant women in the Wa Municipality of Ghana. A cross-sectional study employing systematic random sampling was conducted among 183 consented pregnant women who went for antenatal care in nine health facilities in the Wa Municipality. A structured validated questionnaire was used to collect information about socio-demographic and obstetric characteristics, awareness of Hepatitis B Virus (HBV) transmission and its prevention. Blood samples (3.0 mls) were collected from each participant to test for HBV serum markers using a Wondfo One Step HBV rapid immunochromatographic assay (Catalog number W003) for the Hepatitis B surface antigen (HBsAg). We conducted descriptive statistics including the prevalence and used multivariable logistic regression to determine the risk of Hepatitis B among study participants. Data was analysed using Stata/SE 15. About 20.2% of the 183 pregnant women screened tested positive for HBsAg. Generally, compared with younger pregnant women, older (> = 25) pregnant women were >9 times less likely to test positive for both chronic Hepatitis B core antibody (HBcAb) and (HBeAg) Hepatitis B infections. However, pregnant women in polygamous relationship were more likely to test positive for both (HBcAb) and (HBsAg and HBeAg) Hepatitis B infections compared with those in monogamous relationship. In a multivariable analysis, pregnant women in a polygamous relationships were about 5 times more likely to test positive for HBsAg (AOR = 4.61, 95% CI: 2.06-9.89) and HBcAb (AOR = 4.89, 95% CI:1.52-6.81) and HBeAg (AOR = 4.62, 95% CI:1.21-6.39) compared with those in a monogamous relationship. This study highlights a high HBsAg prevalence among pregnant women with those in polygamous relationship and younger age more likely to test positive. Facility and community-based health services should emphasize the need for regular screening, education, and vaccination of pregnant women, especially those at high risk, to prevent mother-to-child transmission of viral hepatitis B.

Application Study of Neutralization Confirmatory Testing for Low Positive Hepatitis B Surface Antigen.

The high sensitivity of HBsAg quantitative tests has led to some challenges in the qualitative interpretation of weakly positive specimens. This study aimed to explore the clinical utility of neutralization confirma-tory testing for specimens with low positive hepatitis B surface antigen (HBsAg). A retrospective analysis was conducted on outpatient and inpatient cases, from January 2021 to January 2022, at the Zhongshan City People's Hospital, Zhongshan. Confirmatory testing as well as enzyme-linked immunosorbent assay (ELISA) was applied to reanalyze 382 samples with low positive HBsAg detected by chemilumi-nescence microparticle immunoassay (CMIA). A retrospective analysis of hepatitis B serum markers, including e-antigen, e-antibody, and core antibody patterns, was also performed. When the HBsAg value ranged from 0.05 - 0.09 IU/mL, the positivity rate of the confirmatory testing was 34.5%. The HBsAg true positivity levels were all between 0.07 and 0.09. In the range of 0.10 - 0.49, the positivity rate of confirmatory testing was 96.1%. The three methods exhibited a high consistency, when testing samples with relatively high HBsAg values. A receiver operating characteristic (ROC) analysis showed that the optimal sensitivity and specificity were achieved at 0.14 IU/mL. For the HBV e-antigen-positive and negative groups, the positivity rate of confirmatory testing was 100% and 93.8%, with no statistical difference between them. For specimens with weakly positive, low-value HBsAg, particularly when the hepatitis B surface an-tigen level is less than 0.14 IU/mL, neutralization confirmatory testing can serve as a means for further confirmation.

Clinical outcomes of treatment-naïve HBeAg-negative patients with chronic hepatitis B virus infection with low serum HBsAg and undetectable HBV DNA

ABSTRACT Serum hepatitis B surface antigen (HBsAg) level < 100 IU/ml and undetectable hepatitis B virus (HBV) DNA have been recently proposed as an alternate endpoint of “partial cure” in chronic hepatitis B (CHB). We investigated clinical outcomes of hepatitis B e antigen (HBeAg)-negative CHB patients with HBsAg <100 IU/ml and undetectable HBV DNA. Treatment-naïve HBeAg-negative CHB patients with undetectable HBV DNA and normal alanine aminotransferase were retrospectively included from three institutions. Patients were classified into the low HBsAg group (<100 IU/ml) and the high HBsAg group (≥100 IU/ml). Liver fibrosis was evaluated by noninvasive tests (NITs). A total of 1218 patients were included and the median age was 41.5 years. Patients with low HBsAg were older (45.0 vs. 40.0 years, P < 0.001) than those in the high HBsAg group, while the NIT parameters were comparable between groups. During a median follow-up of 25.7 months, patients with low HBsAg achieved a higher HBsAg clearance rate (13.0% vs. 0%, P < 0.001) and a lower rate of significant fibrosis development (2.2% vs. 7.0%, P = 0.049) compared to patients with high HBsAg. No patient developed HCC in either group. HBsAg level was negatively associated with HBsAg clearance (HR 0.213, P < 0.001) and patients with HBsAg < 100 IU/ml had a low risk of significant fibrosis development (HR 0.010, P = 0.002). The optimal cutoff value of HBsAg for predicting HBsAg clearance was 1.1 Log10 IU/ml. Treatment-naïve HBeAg-negative CHB patients with HBsAg <100 IU/ml and undetectable HBV DNA had favourable outcomes with a high rate of HBsAg clearance and a low risk of fibrosis progression.

Mathematical Models of Early Hepatitis B Virus Dynamics in Humanized Mice

Analyzing the impact of the adaptive immune response during acute hepatitis B virus (HBV) infection is essential for understanding disease progression and control. Here we developed mathematical models of HBV infection which either lack terms for adaptive immune responses, or assume adaptive immune responses in the form of cytolytic immune killing, non-cytolytic immune cure, or non-cytolytic-mediated block of viral production. We validated the model that does not include immune responses against temporal serum hepatitis B DNA (sHBV) and temporal serum hepatitis B surface-antigen (HBsAg) experimental data from mice engrafted with human hepatocytes (HEP). Moreover, we validated the immune models against sHBV and HBsAg experimental data from mice engrafted with HEP and human immune system (HEP/HIS). As expected, the model that does not include adaptive immune responses matches the observed high sHBV and HBsAg concentrations in all HEP mice. By contrast, while all immune response models predict reduction in sHBV and HBsAg concentrations in HEP/HIS mice, the Akaike Information Criterion cannot discriminate between non-cytolytic cure (resulting in a class of cells refractory to reinfection) and antiviral block functions (of up to 99%\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$99\\%$$\\end{document} viral production 1–3 weeks following peak viral load). We can, however, reject cytolytic killing, as it can only match the sHBV and HBsAg data when we predict unrealistic levels of hepatocyte loss.

Persistently high HBsAg levels during HBeAg-seropositive stage predict lower risk of hepatocellular carcinoma in chronic hepatitis B patients.

High hepatitis B surface antigen (HBsAg) level predicts hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients with low viral load. The role of longitudinal HBsAg levels in predicting HCC in HBeAg-positive CHB patients remains unknown. HBeAg-positive CHB participants from the REVEAL-HBV cohort with ≥2 HBsAg measurements before HBeAg seroclearance were enrolled. Group-based trajectory modelling identified distinct HBsAg trajectory groups during a median of 11 years of HBeAg-positive status. Cox regression models were applied for investigating independent predictors of HCC and estimating adjusted hazard ratio (HRadj) with a 95% confidence interval (CI). A p-value less than 0.05 was considered statistically significant. A total of 319 patients were enrolled and classified by HBsAg trajectory patterns as (A) persistently high group (n = 72): HBsAg persistently ≥104 IU/mL, and (B) non-stationary group (n = 233): low HBsAg at baseline or declining to <104 IU/mL during the follow-up. Group B had higher proportions of abnormal ALT levels, HBV genotype C and basal core mutation than group A (p < 0.05); age at entry and gender were comparable. The annual incidence of HCC in group A and group B were 0.37% and 1.16%, respectively (p = 0.03). In multivariate analysis, age >40 years (HRadj [95% CI] = 4.11 [2.26-7.48]), genotype C (HRadj [95% CI] = 4.39 [1.96-9.81]) and the non-stationary group (HRadj [95% CI] = 3.50 [1.49-8.21]) were independent predictors of HCC. Basal core promoter mutation was the only risk factor of HCC in the persistently high HBsAg group (HRadj [95% CI] = 32.75 [5.41-198.42]). Patients with persistently high HBsAg levels during HBeAg-seropositive stage represent a unique population with low risk of HCC development.

Incidence and factors associated with hepatitis B surface antigen seroclearance in patients co-infected with HBV/HIV during antiretroviral therapy in Guangdong, China.

Hepatitis B surface antigen (HBsAg) clearance is vital for a functional cure of hepatitis B virus (HBV) infection. However, the incidence and predictors of HBsAg seroclearance in patients co-infected with HBV and human immunodeficiency virus (HIV) remain largely unknown in Guangdong, China. Between 2009 and 2019, patients co-infected with HBV/HIV undergoing antiretroviral therapy (ART) in Guangzhou Eighth People's Hospital affiliated to Guangzhou Medical University were retrospectively reviewed with the endpoint on December 31, 2020. The incidence and risk factors for HBsAg seroclearance were evaluated using Kaplan-Meier and multivariate Cox regression analyses. A total of 1550 HBV/HIV co-infected patients were included in the study, with the median age of 42 years and 86.0% (1333/1550) males. Further, 98.3% (1524/1550) received ART containing tenofovir disoproxil fumarate (TDF) plus lamivudine (3TC). HBV DNA was examined in 1283 cases at the last follow-up. Over the median 4.7 years of follow-up, 8.1% (126/1550) patients achieved HBsAg seroclearance, among whom 50.8% (64/126) obtained hepatitis B surface antibody, 28.1% (137/488) acquired hepatitis B e antigen seroconversion, and 95.9% (1231/1283) undetectable HBV DNA. Compared with patients who maintained HBsAg positive, cases achieving HBsAg seroclearance showed no differences in age, gender, CD4 + T cell count, alanine aminotransferase (ALT) level, or fibrosis status; however, they presented lower HBV DNA levels, lower HBsAg levels, and higher rates of HBV genotype B at the baseline. Multivariate analysis showed that baseline HBsAg <1500 cutoff index (COI) (adjusted hazard ratio [aHR], 2.74, 95% confidence interval [95% CI]: 1.48-5.09), ALT elevation >2 × upper limit of normal during the first six months after receiving ART (aHR, 2.96, 95% CI: 1.53-5.77), and HBV genotype B (aHR, 3.73, 95% CI: 1.46-9.59) were independent predictors for HBsAg seroclearance (all P <0.01). Long-term TDF-containing ART has high anti-HBV efficacy including relatively high overall HBsAg seroclearance in HBV/HIV co-infected patients. Lower baseline HBsAg levels, HBV genotype B, and elevated ALT levels during the first six months of ART are potential predictors of HBsAg seroclearance.

Hepatitis B surface antigen reduction is associated with hepatitis B core-specific CD8+ T cell quality.

Despite treatment, hepatitis B surface antigen (HBsAg) persists in patients with chronic hepatitis B (CHB), suggesting the likely presence of the virus in the body. CD8+ T cell responses are essential for managing viral replication, but their effect on HBsAg levels remains unclear. We studied the traits of activated CD8+ T cells and HBV-specific CD8+ T cells in the blood of CHB patients undergoing nucleos(t)ide analog (NUC) therapy. For the transcriptome profiling of activated CD8+ T cells in peripheral blood mononuclear cells (PBMCs), CD69+ CD8+ T cells were sorted from six donors, and single-cell RNA sequencing (scRNA-seq) analysis was performed. To detect HBV-specific CD8+ T cells, we stimulated PBMCs from 26 donors with overlapping peptides covering the HBs, HBcore, and HBpol regions of genotype A/B/C viruses, cultured for 10 days, and analyzed via multicolor flow cytometry. scRNA-seq data revealed that CD8+ T cell clusters harboring the transcripts involved in the cytolytic functions were frequently observed in donors with high HBsAg levels. Polyfunctional analysis of HBV-specific CD8+ T cells utilized by IFN-γ/TNFα/CD107A/CD137 revealed that HBcore-specific cells exhibited greater polyfunctionality, suggesting that the quality of HBV-specific CD8+ T cells varies among antigens. Moreover, a subset of HBcore-specific CD8+ T cells with lower cytolytic potential was inversely correlated with HBsAg level. Our results revealed a stimulant-dependent qualitative difference in HBV-specific CD8+ T cells in patients with CHB undergoing NUC therapy. Hence, the induction of HBcore-specific CD8+ T cells with lower cytolytic potential could be a new target for reducing HBsAg levels.

Hepatitis B prevention and treatment needs in women in Senegal (ANRS 12356 AmBASS survey)

BackgroundAlthough mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is prevalent in West Africa, epidemiological data on HBV infection in women remain scarce. We studied i) hepatitis B surface antigen (HBsAg) prevalence and its correlates, ii) HBV screening history and serological status awareness, iii) MTCT risk and treatment needs in Senegalese women.MethodsA cross-sectional population-based serosurvey for HBsAg positivity was conducted in 2018–2019 in the rural area of Niakhar (Fatick region, Senegal). Participants were offered home-based HBV screening and answered face-to-face questionnaires. HBsAg-positive participants underwent clinical and biological assessments. Data were weighted and calibrated to be representative of the area’s population. Logistic regression models helped identify factors associated with HBsAg-positivity in adult women (> 15 years old).ResultsHBsAg prevalence in adult women was 9.2% [95% confidence interval: 7.0–11.4]. Factors associated with HBsAg-positivity were being 15–49 years old (ref: ≥ 50), living in a household with > 2 other HBsAg-positive members, and knowing someone with liver disease. Only 1.6% of women had already been tested for HBV; no one who tested HBsAg positive was already aware of their serological status. In women 15–49 years old, 5% risked MTCT and none were eligible for long-term antiviral treatment.ConclusionsAdult women have a high HBsAg prevalence but a low MTCT risk. Low rates of HBV screening and serological status awareness argue for the adoption of systematic screening during pregnancy using free and rapid diagnostic tests. Additionally, screening household members of HBsAg-positive women may greatly improve the cascade of care in rural Senegal.Trial registrationClinicalTrials.gov identifier (NCT number): NCT03215732.

A Systematic Review on Current Trends in the Treatment of Chronic Hepatitis B to Predict Disease Remission and Relapse.

Despite decreasing the prevalence of chronic hepatitis B (CHB), it is still a major health care challenge. Current antiviral regimens aim to suppress hepatitis B virus (HBV) deoxyribonucleic acid (DNA) activity to prevent the risk of hepatic decompensation, liver cirrhosis, and hepatocellular carcinoma (HCC). Currently, pegylated interferon (Peg-IFN) and nucleos(t)ide analogs (NA) are the first-line choices of drugs. Peg-IFN is now discontinued due to its mode of application and side effects. NA is used once daily to suppress HBV DNA activity but has little effect on covalently closed circular DNA (cccDNA), so continuous long-term therapy is required to suppress HBV DNA. Due to this effect, disease remission, relapse, and even clinical flare are common phenomena after the end of treatment (EOT). This review aimed to analyze the current regimens for treating chronic hepatitis B. Their mode of action, duration of treatment, and events after stopping therapy. The review was performed using the preferred reporting items for systematic reviews and meta-analysis (PRISMA) 2020 guidelines. A search was undertaken in PubMed, PubMed Central, Google Scholar, and ScienceDirect. Screening of articles was carried out to find relevant and appropriate articles. Articles were then quality-checked before inclusion. Our analysis showed that long-term finite therapy with nucleoside analogs could improve clinical outcomes and suppress viral DNA activity. However, a functional cure, loss of hepatitis B surface antigen (HBsAg), is rarely achieved. The decision to end treatment depends on quantitative HBsAg level (qHBsAg), alanine aminotransferase (ALT), HBV DNA (deoxyribonucleic acid), hepatitis B e antigen (HBeAg), and fibrosis assessment. It is concluded that patients with HBeAg negative without cirrhosis can be easily withdrawn from treatment if they have long-term viral remission and a high HBsAg loss rate. However, patients with positive HBeAg should continue treatment because there is a high chance of disease relapse and even acute flare. To predict whether patients will benefit from EOT, some immunomodulatory markers are studied, including interleukin (IL-20, IL-8), fas ligand (FASGL), and IFN gamma. Although these factors are reliable, none pose an independent effect on disease remission. Combination therapy (IFN alpha + oral nucleoside analogs) is promising but has clinical shortcomings.

Clinical features of chronic hepatitis B patients with lean nonalcoholic fatty liver disease.

The clinical features have been well described in obese chronic hepatitis B (CHB) patients with nonalcoholic fatty liver disease (NAFLD). However, little is known about the clinical features of lean CHB-NAFLD patients. The study retrospectively included treatment-naïve CHB patients who underwent ultrasound between 2015 and 2021. Liver fibrosis was assessed by aspartate aminotransferase (AST) to platelet ratio index (APRI), Fibrosis-4 score (FIB-4), NAFLD fibrosis score (NFS), and transient elastography. Among 1226 CHB-NAFLD patients, 25.0% patients were lean. The age, gender, and platelet, alanine aminotransferase, AST, and albumin levels were comparable between lean CHB-NAFLD and nonlean patients. The levels of plasma glucose, triglycerides, total cholesterol, and uric acid, as well as proportions of concurrent hypertension and diabetes, were lower in lean patients. Lean patients presented higher hepatitis B surface antigen (HBsAg) levels (3.4 log10 IU/ml vs. 3.2 log10 IU/ml, p=0.006), hepatitis B virus (HBV) DNA levels (4.1 log10 IU/ml vs. 3.2 log10 IU/ml, p<0.001), and hepatitis B e antigen (HBeAg) positive proportions (40.4% vs. 30.2%, p=0.002) than nonlean patients. The values of APRI, FIB-4, and liver stiffness were comparable between two groups. However, lean patients had lower NFS values (-3.0 vs. -2.6, p<0.001) and lower proportions (12.6% vs. 21.1%, p=0.003) of advanced fibrosis (NFS≥-1.5) than nonlean patients. Similar results were observed in HBeAg-positive and HBeAg-negative subgroups. Nearly a quarter of CHB-NAFLD patients were lean. Lean patients had lower proportions of metabolic abnormalities and advanced liver fibrosis than nonlean patients. However, lean CHB-NAFLD patients had higher HBsAg levels, HBV DNA levels, and HBeAg-positive proportions. Registry and registration no. of the study/trial: Clinicaltrials.gov, Identifier: NCT03097952.

A booster hepatitis B vaccine for children with maternal HBsAg positivity before 2 years of age could effectively prevent vaccine breakthrough infections

BackgroundThe long-term protective effect of hepatitis B vaccine (HepB), the incidence of hepatitis B virus (HBV) vaccine breakthrough infections (VBIs), and whether a booster HepB is necessary remain to be clarified in children born to mothers with chronic HBV infection.MethodsBased on a long-term follow-up prospective cohort of 1177 hepatitis B surface antigen (HBsAg)-positive mothers and their paired infants which was established from 2009 to 2011, total 454 children with immunoprophylaxis success as determined by postvaccination serologic testing (PVST) at 7 months old were included in this study. Among the 454 children, 246 never had a booster HepB, and 208 children received a booster HepB from 1 to 5 years of age. Multivariate logistic regression analysis was used to analyse the risk factors for HBV VBIs.ResultsThe hepatitis B surface antibody (anti-HBs) levels declined sharply from 7 months to 2 years old, and the anti-HBs seronegative rate in the children increased significantly from 2 years old. A total of 31 (6.83%) of the 454 children experienced VBIs, of which 7 had overt and 7 had occult HBV infections. Notably, 14 (45.16%) of the 31 children with VBIs were diagnosed at 2 years old, and all of them had anti-HBs positivity (> 10 mIU/mL) at 1 year old. Maternal hepatitis B e antigen (HBeAg) positivity, higher HBV DNA and HBsAg levels, lower initial infant anti-HBs levels and not receiving a booster HepB were independent risk factors for VBIs. The incidence of VBIs was significantly lower in children with a booster HepB than in nonboosted children (0.50 vs. 11.90%, P < 0.001), and none of the boosted children developed overt or occult HBV infection. The anti-HBs levels of 76.67% for the children with VBIs in the nonboosted group indicated positivity before VBIs was detected.ConclusionsAfter the primary full immunization with HepB, children born to mothers with chronic HBV infection, especially the children with maternal HBeAg positivity, high HBV DNA levels, high HBsAg levels and/or low initial infant anti-HBs levels, were at a high risk of VBIs, and a booster HepB for these children before 2 years old, instead of when their anti-HBs level is < 10 mIU/mL, could reduce the incidence of VBIs.

Economic-related inequalities in hepatitis B virus infection among 115.8 million pregnant women in China from 2013 to 2020.

SummaryBackgroundHepatitis B virus (HBV) infection is a serious global health problem and China has the largest disease burden. Literatures focusing on economic-related inequalities in HBV infection among pregnant women are scarce. We aimed to quantify the economic-related inequalities and the change over time in HBV infection among pregnant women in mainland China from 2013 to 2020 to inform strategies considering economic-related inequalities.MethodsWe used national cross-sectional secondary data of pregnant women in 30 provinces from the National Integrated Prevention of Mother-to-Child Transmission of HIV, Syphilis and Hepatitis B Programme (iPMTCT Programme) from 2013 to 2020. We calculated concentration index and adjusted difference between the rich and the poor in the multivariable generalized estimating equation (GEE) model to measure economic-related inequality, after adjusted other risk factors.FindingsIn this study, a total of 115,789,148 pregnant women of mainland China from 2013 to 2020 were included, the overall hepatitis B surface antigen (HBsAg) prevalence was 6.27% (95%CI: 6.26%-6.28%). The curve lay above the equality line, with the negative value of the concentration index of -0.027, which indicated that economic-related health disparities exist in the distribution of HBV infection and the inequality disadvantageous to the poor (pro-poor). The concentration index showed a trend of fluctuating decline, indicating that economic-related inequalities in HBsAg prevalence were narrowing. The adjust difference between counties with lowest economic level and counties with highest economic level (reference group) were 46.3% in HBsAg prevalence (all p<0.05) in the multivariable GEE model, after controlling other confounders. A significant dose-response relationship was observed between low economic level and high HBsAg prevalence that the adjust difference increased from 15.6% (aOR=1.156, 95% CI: 1.064–1.257) in the high-economic group to 46.3% (aOR=1.463, 95% CI: 1.294–1.824) in the lowest-economic group, compared with the highest-economic group. The association between low economic level and high HBsAg prevalence was stable in the sensitivity analysis.InterpretationHBV infection was more concentrated among population with lower economic status. Economic-related inequalities in HBV infection decreased in the past decade. Our findings highlight the importance of developing equity-oriented policies and targeted interventions to reduce HBV infection among the poor and hard-to-reach populations to achieve the 2030 HBV elimination goals on time.Funding10.13039/501100001809National Natural Science Foundation of China.

Immune Mechanisms Underlying Hepatitis B Surface Antigen Seroclearance in Chronic Hepatitis B Patients With Viral Coinfection.

It is considered that chronic hepatitis B patients have obtained functional cure if they get hepatitis B surface antigen (HBsAg) seroclearance after treatment. Serum HBsAg is produced by cccDNA that is extremely difficult to clear and dslDNA that is integrated with host chromosome. High HBsAg serum level leads to failure of host immune system, which makes it unable to produce effective antiviral response required for HBsAg seroclerance. Therefore, it is very difficult to achieve functional cure, and fewer than 1% of chronic hepatitis B patients are cured with antiviral treatment annually. Some chronic hepatitis B patients are coinfected with other chronic viral infections, such as HIV, HCV and HDV, which makes more difficult to cure. However, it is found that the probability of obtaining HBsAg seroclearance in patients with coinfection is higher than that in patients with HBV monoinfection, especially in patients with HBV/HIV coinfection who have an up to 36% of HBsAg 5-year-seroclerance rate. The mechanism of this interesting phenomenon is related to the functional reconstruction of immune system after antiretroviral therapy (ART). The quantity increase and function recovery of HBV specific T cells and B cells, and the higher level of cytokines and chemokines such as IP-10, GM-CSF, promote HBsAg seroclearance. This review summarizes recent studies on the immune factors that have influence on HBsAg seroconversion in the chronic hepatitis B patients with viral coinfection, which might provide new insights for the development of therapeutic approaches to partially restore the specific immune response to HBV and other viruses.

Clinical Utility of SCALE-B to Predict Hepatitis B Virus Relapse, Hepatitis B Surface Antigen Loss After Antiviral Cessation in Asian Patients After 2-Year Follow-up.

BackgroundDiscontinuation of antiviral therapy in chronic hepatitis B (CHB) patients leads to a higher hepatitis B surface antigen (HBsAg) loss; yet, clinical relapse (CR) may occur. SCALE-B score was developed to predict off-treatment CR; however, validation of SCALE-B beyond a 48-week follow-up is rare. We studied whether SCALE-B and hepatitis B virus ribonucleic acid (HBV RNA) could predict outcomes in CHB patients after a 2-year follow-up.MethodsA total of 92 Thai CHB patients who stopped antiviral treatment were followed up; baseline characteristics, quantitative hepatitis B surface antigen (qHBsAg), hepatitis B core-related antigen (HBcrAg), and HBV RNA were collected at the time of discontinuation, and SCALE-B scores were calculated. Patients were followed up every 12 weeks for 48 weeks, and then, the intervals were upon primary doctors. Follow-up data regarding virological relapse (VR), CR, and HBsAg loss were obtained.ResultsThe median follow-up duration was 142 weeks; the cumulative incidences of VR, CR, and HBsAg loss were 65.2, 33.7, and 7.6%, respectively. After 48 weeks, VR and CR plateaued, but HBsAg loss increased from 2.2 to 7.6%. According to the SCALE-B strata, VR, CR, and HBsAg loss were significantly different. The highest stratum (≥ 320) was associated with higher VR, CR, and lesser HBsAg loss when compared to the lowest stratum, with adjusted hazard ratios of 5.0 (95% CIs: 1.8–14.4), 10.44 (95% CIs: 1.4–79.1), and 0.04 (95% CIs: 0.004–0.43), respectively.ConclusionAt a median follow-up of 2.5 years after discontinuing therapy, HBsAg loss in Thai patients was found to increase over time. SCALE-B is a valuable tool for predicting CR, VR, and HBsAg loss; HBV RNA is not significantly associated with long-term outcomes.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [TCTR20180316007].

Finite nucleos(t)ide analogue therapy in hepatitis B e antigen-negative chronic hepatitis B: From an "option" to an "active recommendation".

Nucleos(t)ide analogue (Nuc) including entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide may suppress hepatitis B virus (HBV) DNA profoundly but have no direct action on covalently closed circular DNA, which is a very stable template for HBV production. Therefore, decades of long-term Nuc therapy are required to maintain HBV suppression and to achieve hepatitis B surface antigen (HBsAg) loss in hepatitis B e antigen (HBeAg)-negative patients. However, there are concerns including financial burden, adherence, and willingness for indefinite long-term Nuc therapy. Patients lost to follow-up and hence not monitored may risk severe relapse that may deteriorate to hepatic decompensation or even hepatic failure. Cessation of Nuc therapy in HBeAg-negative patients was initially considered in early 2000s. Earlier findings in Asian patients that finite Nuc therapy over 2-3 years is feasible and safe have founded Asian-Pacific Association for the Study of Liver stopping rule since 2008. Subsequent studies have confirmed the feasibility and safety of the strategy of finite Nuc therapy, which has finally been accepted as "an option" by American and European liver associations since 2016. More recent large studies since 2018 have further confirmed the pivotal finding of greatly increased HBsAg loss rate (~5-year 39%) after stopping Nuc therapy. With the high HBsAg loss rate as the main justification, the paradigm shift from indefinite long-term therapy to finite Nuc therapy in HBeAg-negative patients has been changing from an "option" to an "active recommendation" aiming to achieve HBsAg loss. More studies are needed to fine-tuning the strategy, including research for the optimal duration of consolidation therapy, timing to stop, and to start retreatment.

Analyses of blood donor samples from eight provinces in Lao PDR suggest considerable variation concerning HBV exposure and carriage.

IntroductionHepatitis B is endemic in Lao PDR and about 9% of the adult population is chronically infected. In this study, we investigated regional, occupational, age and sex-related differences in hepatitis B epidemiology in Lao blood donors.Methods5017 voluntary blood donors from 8 different provinces were tested for hepatitis B markers by ELISA. Predictors for the prevalence of hepatitis B surface antigen (HBsAg) and antibodies against the core antigen (anti-HBc) were assessed by bivariate and multivariable analyses.ResultsIn total, 41% of the participants were positive for anti-HBc; the HBsAg prevalence was estimated at 6.9% among all participants (9.2% among first-time donors and 3.9% among repeat donors). Among first-time donors, HBsAg positivity was associated independently with being male (p<0.001), being from the North (p<0.001) and being soldier (p<0.001). Participants were more likely to be anti-HBc positive when they were male (p<0.001), from the Northern provinces (p<0.001) and older than 20 years (p<0.01).ConclusionIn conclusion, our study confirmed an overall high HBsAg and anti-HBc prevalence in Lao PDR, albeit with considerable regional variation. The identification of a sizeable number of HBsAg positives among repeat donors warrants a thorough investigation of current blood screening, record keeping, donor identification and counselling practises.

Mortality of inactive hepatitis B virus carriers in Japan is similar to that of the general population.

Data on the long-term outcomes of individuals with hepatitis B virus (HBV) infection who are hepatitis envelope antigen (HBeAg)-negative inactive carriers (ICs) are limited due to small numbers. We compared the long-term prognosis of well-defined ICs with that of age- and gender-matched general population controls. A total of 526 HBeAg-negative patients who demonstrated alanine aminotransferase (ALT) level ≤40U/L and HBV DNA level ≤4.3 log IU/ml at least three times within 1year after the start of follow-up were enrolled as ICs. Inactive carriers were divided into two groups: Group A (n=332), whose ALT level was ≤30U/L and HBV DNA level was ≤3.3 log IU/ml, and Group B (remaining patients, n=194). We determined the long-term prognosis of ICs and compared it with that of general population controls. We also analyzed factors associated with hepatitis B surface antigen (HBsAg) clearance and phase transition in ICs. There were no significant differences in hepatocellular carcinoma development or all-cause, liver-related, or non-liver-related mortality between Groups A and B. There was no significant difference in all-cause mortality between ICs and the general population. Low HBsAg level (≤3.0 log IU/ml) and the presence of fatty liver were associated with HBsAg clearance and high alpha-fetoprotein level was associated with phase transition. The long-term prognosis of well-defined ICs was similar to that of general population controls. In addition, the ICs had a high HBsAg clearance rate and low phase transition rate.

The relationship between hepatitis B virus serum DNA, RNA and quantitative hepatitis B surface antigen, and the predictive value for mother-to-child transmission: an observational cohort study.

To explore the relationships between hepatitis B virus (HBV) DNA, HBV RNA and hepatitis B surface antigen (HBsAg) and to evaluate their predictive value for mother-to-child transmission of HBV. An observational cohort study. First Hospital of Jilin University. HBsAg-positive and hepatitis B e antigen (HBeAg) -positive pregnant women were recruited. Blood samples were collected from mothers before delivery, and HBV infection of infants was evaluated at 7 months of age. Overall, 268 mothers and 271 infants were enrolled. HBV DNA and HBsAg levels were correlated (rs = 0.699; P < 0.001), and HBV DNA (rs = 0.500; P < 0.001) and HBsAg (rs = 0.372; P < 0.001) were both correlated with HBV RNA. The areas under the curve for HBV DNA, HBsAg and HBV RNA for prediction of infection were 0.69 (95% CI 0.57-0.82), 0.63 (95% CI 0.51-0.76) and 0.65 (95% CI 0.52-0.78), respectively. Higher HBV DNA (odds ratio [OR] 4.77, 95% CI 1.44-15.86), higher HBsAg (OR 4.13, 95% CI 1.12-15.25) and higher HBV RNA (OR 3.19, 95% CI 1.09-9.32) were risk factors for HBV infection. Analysis of the HBV DNA-RNA-HBsAg Score revealed that it was an independent predictive factor for mother-to-child transmission (the OR of Score 3 was 8.81, 95% CI 2.79-27.82). HBV DNA, HBV RNA and HBsAg were correlated in HBeAg-positive pregnant women. HBsAg could be considered as a substitute marker of HBV DNA for HBeAg-positive pregnant women in low-income regions. We should pay special attention to pregnant women with high levels of all three markers. HBsAg could be considered as a substitute marker of HBV DNA for HBeAg-positive pregnant women in low-income regions. Special attention should be given to pregnant women with high levels of all three markers (HBV DNA, HBV RNA and HBsAg).

Hepatitis B Core-Related Antigen is a Biomarker for off-Treatment Relapse After Long-Term Nucleos(t)ide Analog Therapy in Patients with Chronic Hepatitis B.

ObjectiveIt remains unknown how to stratify the risk of clinical relapse of chronic hepatitis B (CHB) patients after stopping nucleos(t)ide analogs (NAs) antiviral therapy.MethodsThe current post hoc analysis included 122 non-cirrhotic patients with chronic hepatitis B virus infection who were positive for hepatitis B envelope antigen (HBeAg) and discontinued long-term NA therapy after achieving HBeAg seroconversion for a median of 2.5 years. Post hoc analysis of end-of-treatment (EOT) hepatitis B core-related antigen (HBcrAg) levels was performed using a chemiluminescent enzyme immunoassay.ResultsA total of 78/122 (63.9%) patients experienced sustained response after NAs cessation, and 44/122 (36.1%) patients experienced clinical relapse. In multivariate analysis, EOT HBcrAg (hazard ratio [HR] = 2.105 95% CI: 1.440–3.077, p < 0.001), hepatitis B surface antigen (HBsAg) ≥100 IU/mL (HR = 4.406, 95% CI 1.567–12.389, p = 0.005) and age (HR = 1.051, 95% CI: 1.010–1.093, p = 0.049) were independently associated with clinical relapse. A cut-off value of 4.0 log10 U/mL of HBcrAg was defined by maximized Youden’s index. An EOT HBcrAg level of ≥4.0 log10 U/mL was associated with higher risks of clinical relapse (65.8% vs 23.2%, p<0.001) and HBeAg reversion (27.5% vs 1.6%, p < 0.001). In majority of patients (n = 91) who had a high EOT HBsAg level (≥100 IU/mL), serum HBcrAg level could further discriminate patients at low risk of clinical relapse. Patients with an HBcrAg level ≥4.0 log10 U/mL had significantly higher cumulative incidence rates of clinical relapse (78.1% vs 29.4%, p < 0.001) and HBeAg reversion (29.4% vs 0%, p < 0.001).ConclusionSerum EOT HBcrAg level can be a predictor of off-treatment relapse in patients with CHB. An HBcrAg level of 4.0 log10 U/mL may identify patients at high risk of clinical relapse after treatment cessation.

Challenges and opportunities for hepatitis B cure in the setting of HIV--hepatitis B virus co-infection.

To examine issues specific to HIV--HBV co-infection that are relevant to the search for and achieving hepatitis B cure in this the setting RECENT FINDINGS: In HIV--HBV co-infection, high rates of hepatitis B surface antigen (HBsAg) loss early after initiation of HBV-active antiretroviral therapy (ART) have previously been reported. Between 2012 and 2016, HBsAg loss from 2.8 to 23% was reported in numerous studies, including those already on suppressive HBV-active ART. Data published in 2018-2019 show that these rates have remained fairly stable (3.0-13.9%). However, it appears that higher HBsAg loss on starting HBV-active ART in co-infection falls within a few years to levels similar to that observed in long-term treated HBV mono-infection. Immune reconstitution and CD4+ T-cell recovery are likely to play a role in high HBsAg loss rates seen in early treated co-infection, although the mechanisms driving this are yet to be fully elucidated. High rates of HBsAg loss early after HBV-active ART initiation is unique to HIV--HBV co-infection, making it the ideal setting to investigate underlying mechanisms of HBV loss and develop new HBV cure strategies. This phenomenon could be used to enhance HBsAg loss with new therapeutic approaches currently being investigated; however, this is obstructed by excluding co-infection from such studies.