One of the key features of chronic hepatitis B virus (HBV) infection is the inability to mount sufficient and coordinated adaptive immune responses against HBV. Recent studies on HBV-specific B cells and antibody to hepatitis B surface antigen (anti-HBs) have shed light on their role in the pathogenesis of chronic hepatitis B (CHB). Anti-HBs is recognized as a protective immune marker, both for HBV infection clearance and following vaccination, and it is also considered an important indicator of functional cure for CHB. Notably, functional impairment of HBV-specific B cells may be reversible. The restoration of HBV-specific B cell function, along with the induction of an anti-HBs antibody response, is regarded as pivotal for terminating chronic HBV infection and achieving functional cure. This article reviews the significance of anti-HBs in both the infection and clearance of HBV, and discusses the potential of neutralizing antibodies and therapeutic vaccines as promising future strategies.

A notable proportion of CHB patients undergoing PEG-IFNα based therapy experience lagged serum HBeAg and/or HBV DNA disappearance in patients achieving HBsAg loss. In this study, we explored the molecular mechanisms behind this clinical phenomenon, offering novel insights into the sustainability of chronic HBV infection.

Two independent clinical cohorts were enrolled to validate this phenomenon. Then comprehensive analysis was performed using public datasets, coupled with a series of molecular biology experiments.

Approximately 17-20% CHB patients underwent PEG-IFNα based therapy experienced seroclearance of HBsAg, while serum HBeAg and/or HBV DNA remained positive. These patients are more prone to serum HBsAg reappearance compared to those achieving complete virological response. Analysis of public datasets revealed that compared to the PC/BCP, the SP1/SP2 promoter displayed more pronounced inhibitory epigenetic modifications in HBeAg-negative patients and SP1/SP2 in-frame mutation peaked in immune active patients. In vitro experiments demonstrated that introduced SP1/SP2 inactive mutations would enhance PC/BCP transcriptional activity by a mechanism known as adjacent transcriptional interference. Furthermore, the deletion of L-HBsAg facilitated intracellular cccDNA replenishment.

This study elucidates that under IFNα treatment and low viral load, transcriptional suppression of SP1/SP2 promoters through mutations and/or epigenetic changes would favour the maintenance of sustain chronic HBV infection, via enhancing the transcription activity of BCP to promote cccDNA replenishment.

In clinical practice with IFNα antiviral treatment for CHB patients, a "paradoxical" phenomenon is observed where serum HBsAg disappears while HBV DNA or/and HBeAg remains at low positive levels, with delayed disappearance. Our study confirms this clinical phenomenon using two independent clinical cohorts and explores the potential mechanisms behind the persistence of chronic HBV infection under IFNα treatment and low viral load. Transcriptional suppression of SP1/SP2 promoters through mutations and/or epigenetic changes supports the maintenance of chronic HBV infection by enhancing the transcriptional activity of the BCP, which in turn promotes cccDNA replenishment.

HighlightsApproximately 20% of patients with CHB who have just achieved HBsAg loss under IFNα treatment show positive serum HBV DNA and/or HBeAg.During disease progression, in frame indel mutations accumulate in the HBV genome's SP1 and SP2 promoters, with epigenetic modifications contributing to their suppression.In frame indel mutations in the HBV genome's SP1 and SP2 promoters inhibit the transcription of HBV S mRNA and promote the transcription of 3.5 kb HBV RNA.The loss of L-HBs and envelop proteins leads to an increase in intracellular cccDNA, promoting the maintenance of chronic infection.

Hepatitis B virus (HBV) is a leading cause of chronic hepatitis and remains a significant global public health concern due to the lack of effective treatments. HBV replicates through reverse transcription within the viral capsid, making capsid assembly a promising antiviral target. However, no approved therapies currently target this process. In our previous study, we optimized the structure-activity relationship (SAR) of NVR 3-778 by modifying the A and B rings, leading to the identification of KR-26556 and Compound 3. In this study, we further synthesized derivatives to modify the C ring, resulting in the discovery of KR019 and KR026. These compounds exhibited over 170-fold higher selectivity than the reference compound while demonstrating potent antiviral activity in HBV-replicating cells. Mechanistic studies revealed that KR019 binds to the hydrophobic pocket at the core protein dimer-dimer interface, misdirecting capsid assembly into genome-free capsids and thereby inhibiting viral replication. Additionally, pharmacokinetic profiling confirmed favorable stability and safety. These findings highlight the strong antiviral potential of KR019 and KR026 and provide a foundation for further in vivo investigation.

HCC is the most common type of primary liver cancer and is a common malignancy worldwide. About half of all new liver cancers worldwide each year occur in China, including Hong Kong, due to a high prevalence of HBV infection. HBV DNA integrates into the human genome, disrupting the endogenous tumor suppressors/regulatory genes or enhancing the activity of proto-oncogenes. It would be useful to examine the different NGS-based databases to provide a more unbiased and comprehensive survey of HBV integration.

We aimed to take advantage of publicly available data sets of different regional cohorts to determine the disparity landscapes of integration events among sample cohorts, tissue types, chromosomal positions, individual host, and viral genes, as well as genic locations. By comparing HCC tumors with non tumorous livers, the landscape of HBV integration was delineated in gene-independent and gene-dependent manners. Moreover, we performed mechanistic investigations on how HBV-TERT integration led to TERT activation and derived a score to predict patients' prognostication according to their clonal disparity landscape of HBV integration.

Our study uncovered the different levels of clonal enrichment of HBV integration and identified mechanistic insights and prognostic biomarkers. This strengthens our understanding of HBV-associated hepatocarcinogenesis.

The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents a significant global public health threat. Concurrently, hepatitis B virus (HBV) remains a significant public health challenge. While previous studies have indicated an association between COVID-19 and chronic hepatitis B, the common underlying pathogenesis of these diseases remains incompletely understood.

To investigate the shared molecular mechanisms between chronic HBV infection and COVID-19, a comprehensive investigation was conducted using bioinformatics and systems biology. Specifically, we utilized RNA-seq datasets (GSE196822 and GSE83148) to identify differentially expressed genes (DEGs) associated with both SARS-CoV-2 and HBV infection. Subsequently, these common DEGs were utilized to identify shared pathways, hub genes, transcriptional regulatory networks, and potential drugs. The differential expression of hub genes in both COVID-19 and HBV was verified using the GSE171110 and GSE94660 datasets, respectively.

From the 106 shared DEGs identified, immune-related pathways were found to play a role in the development and progression of chronic hepatitis B and COVID-19. Protein-protein interaction (PPI) network analysis revealed 8 hub genes: CDK1, E2F7, E2F8, TYMS, KIF20A, CENPE, TPX2, HMMR, CD8A, GZMA. In the validation set, the expression of hub genes was statistically significant in both the COVID-19 group and the HBV group compared with the healthy control group. Transcriptional regulatory network analysis identified 155 microRNAs (miRNAs) and 43 transcription factors (TFs) as potential regulatory signals. Notably, we identified potential therapeutic drugs for HBV chronic infection and COVID-19, including progesterone, estradiol, dasatinib, aspirin, etoposide, irinotecan hydrochloride, phorbol 12-myristate 13-acetate, lucanthone, calcitriol.

This research elucidates potential molecular targets, signaling pathways, and promising small molecule compounds that could aid in the treatment of chronic HBV infection and COVID-19.

Hepatitis B virus (HBV) is a causative agent for chronic liver hepatitis, which confers risk for liver cirrhosis and hepatocellular carcinoma. Among key viral transcripts, HBV pregenome RNA (pgRNA) is indispensable for viral replication, and therefore, quality control of pgRNA is critical for the HBV life cycle. Here, we revealed degradation of HBV RNAs by the nonsense-mediated mRNA decay (NMD) pathway, a host surveillance system of RNA quality. Degradation kinetics of the HBV RNAs indicated that pgRNA, 2.4 knt RNA, and 2.1 knt RNA were targets of the NMD pathway and also interacted robustly with phosphorylated UPF1 but not X RNA. Northern blotting showed that decay of the viral NMD candidates was also delayed in NMD-deficient cells. In contrast, NMD depletion promoted the formation of capsids containing genomic DNA and exhibiting antigen production. Our data strongly suggest that the NMD pathway inspects HBV transcripts to regulate HBV replication as an intrinsic antiviral defense.

Cell death occurs continuously throughout individual development. By removing damaged or senescent cells, cell death not only facilitates morphogenesis during the developmental process, but also contributes to maintaining homeostasis after birth. In addition, cell death reduces the spread of pathogens by eliminating infected cells. Cell death is categorized into two main forms: necrosis and programmed cell death. Programmed cell death encompasses several types, including autophagy, pyroptosis, apoptosis, necroptosis, ferroptosis, and PANoptosis. Autophagy, a mechanism of cell death that maintains cellular equilibrium via the breakdown and reutilization of proteins and organelles, is implicated in regulating almost all forms of cell death in pathological contexts. Notably, necroptosis, ferroptosis, and PANoptosis are directly classified as autophagy-mediated cell death. Therefore, regulating autophagy presents a therapeutic approach for treating diseases such as inflammation and tumors that arise from abnormalities in other forms of programmed cell death. This review focuses on the crosstalk between autophagy and other programmed cell death modalities, providing new perspectives for clinical interventions in inflammatory and neoplastic diseases.

The use of methylprednisolone (MP) is still controversial for hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF). We aimed to explore the change in dendritic cells (DCs) during MP treatment in HBV-ACLF to guide the use of MP to improve patient's prognosis.

Patients with HBV-ACLF were prospectively allocated to groups given methylprednisolone intravenously (1.5 mg/kg/day for the first 3 days, 1 mg/kg/day for the second 2 days, and 0.5 mg/kg/day for the last 2 days, MP group, n = 36) plus standard treatment or standard treatment only (CM group, n = 34). The phenotype [myeloid and plasmacytoid DCs (mDCs, pDCs)] and function of DCs (IL-12 and IFN-α production) were measured at baseline (0d), 3d, 7d, 10d, 14d, 28d, and then monthly until 3 months. Patients' survival was assessed until day 90.

The 3-month survival rate was significantly higher in the MP group than the control (72.0 % vs. 35.5 %，P < 0.01). The phenotype and function of DCs were suppressed in the MP group. The mDCs counts was lower in non-survivors compared to survivors at baseline. Patients with a decline in mDCs counts at the 7th day and a continuous increase in mDCs counts from the 10th day presented a better outcome for patients with MP treatment. Bilirubin was the only relative factor for the restoration of mDCs in the MP group (odds ratio, 0.991; 95 % confidence interval, 0.984-0.999; P = 0.023).

Methylprednisolone could improve the outcome of HBV-ACLF by inhibiting the circulating mDCs counts. And the recovery of mDCs counts after methylprednisolone treatment could represent a favorable response. We can consider monitoring the circulating DCs counts to guide the use of MP in HBV-ACLF in order to improve patient outcomes.

Chronic hepatitis B virus (HBV) infection affects approximately 254 million individuals globally, contributing to significant morbidity and mortality due to HBV-related liver failure and cirrhosis, which result in millions of fatalities each year. Although approved antiviral nucleos(t)ide analogues can effectively suppress HBV replication, their ability to reduce hepatitis B surface antigen (HBsAg) levels in plasma remains limited. The clinical application of the immunomodulator interferon-alpha is restricted by concerns regarding its safety and the severity of associated adverse reactions, rendering long-term administration challenging. Therefore, current drug development efforts for chronic hepatitis B aim to achieve a functional cure, which is defined as HBsAg serological clearance and sustained suppression of HBV DNA. This review discusses recent advancements in novel direct-acting therapeutic strategies for the treatment of chronic hepatitis B by focusing on the progresses in HBV entry inhibitors, monoclonal antibodies, RNA interferences, and other agents that directly target the virus. Furthermore, we discuss the development of immunomodulatory therapies, including TLR-7/8 agonists, immune checkpoint inhibitors, and therapeutic vaccines. In the end, we conclude by highlighting the importance of the rational combination-strategy design to improve the functional cure rate of HBV.

The high prevalence of hepatitis B weighs heavily on public health in China. In 2009, a catch-up vaccination program for children aged 8-15y was implemented to curb hepatitis B, while the effectiveness of this intervention has not been investigated. We aimed to evaluate the effectiveness of catch-up vaccination on the incidence of hepatitis B in Guangzhou, China.

We obtained individual data of all hepatitis B cases from 2005 to 2019 in Guangzhou from Guangzhou Center for Diseases Control and Prevention. Based on daily reported number of cases, we constructed generalized linear models to estimate the effectiveness of the intervention on the incidence of hepatitis B in each age group from 11 to 25 years. We further estimated the age-standardized effectiveness. Finally, we examined the effectiveness in different subgroups by sex and clinical types of hepatitis B.

A total of 58,204 hepatitis B cases among individuals aged 11-25y were reported in Guangzhou from 2005 to 2019, with an average annual age-standardized incidence of 117.30 cases per 100,000 individuals. The catch-up vaccination contributed to an age-standardized 20.02% (95% confidence interval: 15.97%, 23.87%) decrease in the hepatitis B incidence among individuals aged 11-25y and prevented an annual age-standardized average of 17.40 (95% empirical confidence interval [eCI]: 9.24, 23.78) cases per 100,000 individuals from hepatitis B during the study period. The intervention could better protect males (excess incidence rate [EIR]: -21.82 [95% eCI: -30.51, -10.15] cases per 100,000 individuals), and prevent chronic cases (EIR: -24.27 [95% eCI: -30.62, -16.09] cases per 100,000 individuals).

The massive catch-up vaccination against hepatitis B among children plays an important role in alleviating the burden of hepatitis B.

Objective The progression of liver fibrosis and a male sex are risk factors for hepatocarcinogenesis under nucleos(t)ide analog (NA) therapy. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a risk factor for hepatocarcinogenesis. This study aimed to investigate the factors involved in hepatocarcinogenesis during NAs therapy, including MAFLD. Methods This study is a retrospective study [observation period: median 9.4 years (2.1-19.6 years)]. The subjects were 164 patients taking NAs for more than 2 years and were hepatitis B envelope antigen (HBeAg)-negative with undetectable hepatitis B virus (HBV)-DNA. The patient had no history of hepatocellular carcinoma (HCC). We investigated the profile of HCC onset after NAs therapy using a decision tree analysis Results HCC developed in 20.7% (34/164) of the patients during the observation period. The prevalence of MAFLD was significantly higher in the HCC group than in the non-HCC group (64.7% vs. 43.9%, p=0.03). In particular, in the low-medium risk group classified by PAGE-B, MAFLD increased the risk of HCC development. According to a multivariate analysis, fibrosis-4 (FIB-4) index≥2.67, a male sex, and MAFLD (OR 2.4, 95%CI 1.0-6.0, p=0.04) were independent factors associated with the onset of HCC. In a decision tree analysis, MAFLD was the second classifier for the onset of HCC, next to the FIB-4 index (MAFLD 62.5%, non-MAFLD 28.5%). Conclusions We found that MAFLD was an independent risk factor for HCC in HBeAg-negative patients with undetectable HBV-DNA after NAs therapy. We further revealed that MAFLD was the second-best classifier for hepatocarcinogenesis, next to the FIB-4 index. MAFLD therefore appears to have a synergistic effect on hepatocarcinogenesis with hepatic fibrosis.

Functional cure strategies based on interferon therapy for chronic hepatitis B (CHB) are gaining increasing attention among clinicians. However, studies investigating the duration of response after achieving HBsAg clearance with interferon treatment are limited. This study aims to explore the patterns of sustained response following HBsAg clearance in patients treated with pegylated interferon alpha-2b (PegIFNα-2b) through long-term follow-up, providing guidance for clinical practice.

We collected data from CHB patients who achieved HBsAg clearance and were treated with either PegIFNα-2b monotherapy or in combination with nucleos(t)ide analogs (NAs) at Tianjin Third Central Hospital from January 2018 to May 2024. Regular follow-up assessments were conducted to observe the dynamic changes in HBsAg, HBV DNA, and liver function during the follow-up period. We recorded the time to HBsAg reversion (defined as HBsAg ≥ 0.05 IU/mL), analyzed the patterns of HBsAg reversion, and investigated the optimal time points for evaluating sustained HBsAg clearance.

A total of 173 patients with CHB or compensated hepatitis B cirrhosis were included. The mean age was 41.5 ± 9.0 years, with 16.19% of patients having compensated cirrhosis. The median follow-up duration was 89.3 weeks (range: 18.6 to 289.1 weeks). HBsAg reversion occurred in 26 patients, yielding a reversion rate of 15.03% (26/173). Among these 26 patients, 50% (13/26) experienced reversion within 24 weeks, and 80.77% within 48 weeks; thereafter, the number of reversions gradually decreased. At 48 weeks post-treatment cessation, the HBsAg sustained response rate was 95.45%, stabilizing at 100% after 120 weeks. Among patients with regular follow-ups, virtually none experienced reversion beyond 72 weeks. At the time of HBsAg reversion, all 26 patients exhibited normal alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) levels, with a median HBsAg level of 0.70 IU/mL (range: 0.05 to 8.13 IU/mL), and only one patient showing low-level positive HBV DNA (117 IU/mL). No adverse events, including liver failure, decompensation, or hepatocellular carcinoma, occurred during the follow-up period.

Patients with chronic hepatitis B treated with PegIFNα-2b demonstrated favorable long-term persistence of HBsAg clearance. However, there remains a risk of HBsAg reversion after treatment cessation, predominantly within the first 48 weeks. HBsAg sustained response (HSR) at 48 weeks post-treatment is a critical follow-up time point for CHB patients post-HBsAg clearance, with HSR at 72 weeks potentially representing an ideal follow-up timeframe, while HSR at 120 weeks may serve as a marker for extended follow-up.

The Association of Ringside Physicians (ARP) emphasizes the importance of screening combat sports athletes for blood-borne infections, including hepatitis B, HIV, and hepatitis C, to mitigate transmission risks and ensure participant safety. Although transmission of hepatitis B and C and HIV in combat sports is rare, protecting athletes is of utmost importance. It is the recommendation of the ARP that all fighters participating in combat sports, in which the presence of blood is a common occurrence and is allowed during competition, should undergo testing for HIV, hepatitis B (HBV), and hepatitis C (HCV). Testing should be conducted using serum samples, because rapid tests are not considered acceptable for accurate results. Testing for HBV, HCV, and HIV should optimally be done within 3 months of competition, but within 6 months is acceptable. Athletes whose tests suggest active HBV, HCV, or HIV infection should be disqualified from competition in sports where blood is common and allowed. Athletes with cured prior HCV infection may be cleared for competition in all combat sports. Athletes with prior HBV infection and no detectable HBV DNA in blood can be cleared for competition in all combat sports. Athletes with latent HBV infection with detectable HBV DNA in blood have a small risk of disease reactivation, so they should not be cleared.

Tenofovir amibufenamide (TMF) has demonstrated significant antiviral activity and safety in individuals with chronic hepatitis B (CHB) in randomized clinical trials. The purpose of this study was to investigate the effectiveness and safety disparities between TMF and Tenofovir alafenamide (TAF) in treating elderly patients with decompensated hepatitis B cirrhosis in real-world settings.

A retrospective cohort analysis of elderly patients with decompensated hepatitis B cirrhosis who were treated with TMF or TAF in our hospital's outpatient department between January 2022 and December 2023 was the focus of this study. Following a 24-week treatment period, this study evaluated the disparities between the TMF and TAF groups in terms of primary efficacy endpoints (virologic response rate, VR rate), secondary efficacy endpoints (normalization rate of ALT, HBsAg and HBeAg clearance rate, HBsAg and HBeAg seroconversion rates), as well as safety endpoints related to renal function and blood lipids.

The study included 171 patients (93 in the experimental group and 78 in the control group). Following a 24-week treatment period, HBV DNA, HBsAg, ALT, AST, and TBIL had significantly decreased compared to the baseline level, and the differences were statistically difference. Cr, eGFR, triglyceride, and TG had no significant changes compared with the baseline level, and the differences were no statistical difference. The virologic response rate in the experimental group was 70.97% (33/93), and that in the control group was 73.08% (57/78), with no statistical difference observed between the two groups (P = 0.760). ALT normalization rate was 83.33% in the experimental group and that was 100% in the control group, and there was not a statistically significant distinction between the two groups (P = 0.229). Compared with baseline data, Cr and eGFR of the experimental group increased (2.97 ± 14.66 μmol/L, P = 0.867; 0.29 ± 6.76 mL/min/1.72 m2, P = 0.680), TC and TG decreased (-0.5 ± 1.30 mmol/L, P = 0.589; -0.006 ± 0.23 mmol/L, P = 0.986), however, no statistical difference was observed. Compared with the control group, the change of safety dates was also no statistical difference.

TMF treatment in elderly patients with decompensated hepatitis B cirrhosis had a good antiviral effect, no adverse drug reaction on renal function and blood lipids, and high safety. TMF is not inferior to TAF in antiviral efficacy and safety.

Hepatitis B virus (HBV) RNA is an important serum biomarker of hepatic covalently closed circular DNA (cccDNA) transcriptional activity; however, its clinical characteristics remain unclear. This study evaluated the clinical utility of HBV RNA levels in patients with chronic hepatitis B (CHB).

We studied 87 CHB patients with serum HBV DNA levels ≥ 5.0 log IU/mL who initiated entecavir (ETV) treatment between 2000 and 2018. Serum HBV RNA levels were measured at three-time points: before ETV treatment, at 12 weeks, and at 48 weeks after starting ETV treatment. Clinical markers associated with the antiviral effects of ETV treatment were analyzed.

Serum HBV RNA levels decreased in both HBeAg-positive and -negative patients during the observation period. In HBeAg-positive patients, multivariable analysis showed that lower HBV RNA levels at 48 weeks of ETV treatment were independently associated with HBeAg seroconversion. Additionally, lower baseline HBV RNA levels significantly predicted virologic response in those patients. In contrast, among HBeAg-negative patients, lower HBV core-related antigen (HBcrAg) levels and the FIB-4 index were independently associated with virologic response. In HBeAg-positive patients, those with higher baseline HBV RNA levels showed a more significant reduction in hepatitis B surface antigen levels.

Serum HBV RNA levels predicted HBeAg seroconversion and early HBV DNA reduction in HBeAg-positive patients, while HBcrAg was significantly associated with virologic response in HBeAg-negative patients. These findings highlight the different predictive roles of HBV RNA and HBcrAg based on HBeAg status, which may provide individualized treatment strategies.

We evaluated the diagnostic accuracy of various international guideline criteria for identifying HBeAg-positive chronic HBV infection patients with no significant liver disease. A total of 1108 HBeAg-positive CHB patients were retrospectively enrolled. The guidelines assessed included those from the European Association for the Study of the Liver (EASL) 2017, the American Association for the Study of the Liver Disease (AASLD) 2018, the Asian Pacific Association for the Study of the Liver (APASL) 2015 and the Chinese Society of Hepatology (CSH) 2022. The CSH criteria demonstrated a higher proportion of patients with G0-1 and S0-1 (82.9%) compared to the EASL (75.9%), AASLD (75.3%) and APASL groups (58.8%). Additionally, the CSH criteria exhibited a significantly higher predictive value (AUC 0.782, 95% CI 0.754-0.809) than the EASL (AUC 0.765, 95% CI 0.737-0.793), AASLD (AUC 0.749, 95% CI 0.720-0.778) and APASL (AUC 0.720, 95% CI 0.690-0.750) criteria for identifying G0-1 and S0-1. Adding quantitative HBsAg levels (> 104 IU/mL) to the EASL, AASLD and APASL criteria improved diagnostic performance. Consequently, the CSH guideline thresholds showed higher accuracy in identifying Chinese HBeAg-positive patients with no significant liver disease compared to EASL, AASLD and APASL criteria, emphasising the importance of considering quantitative HBsAg in the evaluation of HBeAg-positive chronic HBV infection.

Despite significant advances in chronic hepatitis B (CHB) treatment, some patients receiving entecavir (ETV) still experience poor clinical outcomes. Identifying host factors contributing to ETV anti-HBV failure in CHB patients with persistent HBV DNA positivity is crucial for developing targeted therapies. We conducted a comprehensive study using univariate and reverse Mendelian randomization (MR), incorporating sequencing data and publicly available genetic data, followed by gene set variation analysis (GSVA), gene set enrichment analysis (GSEA) and immune cell infiltration analysis to systematically explore causal associations between host factors and CHB. Univariate MR analyses revealed a significant inverse association between increased HLA-DRB1 levels and CHB risk (odds ratio [OR] 0.607, 95% confidence interval [CI] 0.478-0.771, p = 0.00004), while increased LGALSL levels were significantly associated with a heightened risk of poor CHB prognosis (OR 1.110, 95% CI: 1.017-1.212, p = 0.01885), as estimated using the inverse variance weighting (IVW) method. Analysis of immune cell infiltration showed significantly higher HLA and mast cell levels in the poor prognosis group. HLA-DRB1 showed a significant positive correlation with HLA, whereas LGALSL showed a significant negative correlation. Compared to patients with favorable prognoses, those with poor prognoses exhibited significantly higher serum LGALSL levels (ELISA), lower HLA-DRB1 expression in peripheral blood mononuclear cells (PBMCs) (qPCR), and significantly increased LGALSL expression in liver tissue (IHC). Therefore, LGALSL and HLA-DRB1 may serve as potential prognostic biomarkers for CHB patients receiving ETV, providing novel avenues for diagnosis and treatment.

Chronic hepatitis B (CHB) remains a significant global health challenge, and effective antiviral therapies are essential for long-term management. This study aimed to evaluate the real-world effectiveness and safety of tenofovir amibufenamide (TMF) in a cohort of patients with chronic hepatitis B (CHB).

In this multicenter, prospective, real-world cohort study, 194 CHB patients were recruited from four hospitals between August 2021 and August 2022. Patients were divided into treatment-naïve (TN, n = 123) and treatment-experienced (TE, n = 71) groups. The TN group was further subdivided into TMF (n = 63) and tenofovir disoproxil fumarate (TDF, n = 60) subgroups. In the TE group, patients transitioned from prior antiviral therapies (entecavir or TDF) to TMF after meeting criteria for poor virological response or safety concerns. Treatment response was evaluated in terms of virological effectiveness and alanine transaminase normalization rates. Virological response (VR), ALT normalization rates, renal function markers, and lipid profiles were monitored.

In the TN cohort, VR rates at 24 and 48 weeks were 42.86% and 90.48% for TMF, and 60.00% and 83.33% for TDF. ALT normalization rates at 24 and 48 weeks for TMF were 56.82% and 70.45% (according to AASLD 2018 standards). In the TE group, VR rates at 24 and 48 weeks were 83.1% and 91.55%, respectively. ALT normalization rates were 86.67% and 93.33% (local standards), and 66.67% and 76.67% (AASLD 2018 standards) (z = -2.822, P = 0.005). Additionally, TMF showed improved renal safety over TDF, with no significant differences in lipid concentrations.

TMF is comparable to TDF in terms of CHB treatment effectiveness, with better renal safety and no impact on lipid levels. In TE patients, transitioning to TMF therapy does not affect antiviral treatment outcomes.

Liver cancer is the third leading cause of death globally, with hepatitis B virus (HBV) infection being identified as the primary risk factor for its development. The occurrence of HBV-related hepatocellular carcinoma (HCC) is attributed to various mechanisms, such as chronic inflammation and liver cell regeneration induced by the cytotoxic immune response triggered by the virus, abnormal activation of oncogenes arising from HBV DNA insertion mutations, and epigenetic alterations mediated by viral oncoproteins. The envelope protein of the HBV virus, known as hepatitis B surface antigen (HBsAg), is a key indicator of increased risk for developing HCC in HBsAg-positive individuals. The HBsAg seroclearance status is found to be associated with recurrence in HCC patients undergoing hepatectomy. Additional evidence indicates that HBsAg is essential to the entire process of tumor development, from initiation to advancement, and acts as an oncoprotein involved in accelerating tumor progression. This review comprehensively analyzes the extensive effects and internal mechanisms of HBsAg during the various stages of the initiation and progression of HCC. Furthermore, it highlights the importance and potential applications of HBsAg in the realms of HCC early diagnosis and personalized therapeutic interventions. An in-depth understanding of the molecular mechanism of HBsAg in the occurrence and development of HCC is provided, which is expected to develop more precise and efficient strategies for the prevention and management of HCC in the future.

Objectives: Chronic Hepatitis B virus (HBV) infection is a significant global health issue, with dialysis patients at increased risk and reduced response to HBV vaccination. The effects of HBV serological status on kidney transplant outcomes, particularly for patients with resolved or inactive HBV infection, needs more data, especially from current era. This study evaluated the impact of chronic and non-active HBV infection on patient and graft survival after kidney transplantation. Methods: Retrospective analysis was conducted of kidney-only transplant recipients at our center from 1 January 1990 to 31 August 2019 (end of observation). Patients were grouped by their HBV serostatus before transplantation into three categories: HBV negative (HBsAg-/Anti-Hbc-), non-active HBV infection (HbsAg-/Anti-Hbc+) and chronic HBV infection (HbsAg+/Anti-Hbc+). Primary outcomes included patient survival, graft survival, and overall graft and patient survival, analyzed using Kaplan-Meier (KM) curves, log-rank tests, Restricted mean survival times (RMST), and Accelerated failure time (AFT) models. Results: Among 2490 patients, 2197 were HBV negative, 218 had non-active HBV, and 75 had chronic HBV. Over a mean follow-up of 8.1 years, mortality and graft failure rates were highest in chronic HBV patients (49% and 37%), followed by non-active HBV (39% and 29%) and HBV-negative patients (30% and 20%). KM analysis revealed significantly lower overall survival rates for chronic HBV and non-active HBV groups compared to HBV-negative patients (p = 0.006). RMST confirmed significant reductions in survival for the non-active group (12.57 vs. 14.17 years, p = 0.007). Cox regression and AFT models identified older recipient/donor age, Hepatitis-C-virus coinfection, and broad antigen mismatches as negative predictors, while living donors improved outcomes. Conclusions: While unadjusted Kaplan-Meier curves and RMST analysis suggested differences in patient and graft survival, further thorough multivariable AFT analysis did not show a significant association between non-active or chronic HBV infection and patient or graft survival after kidney transplantation.

To refine the 23-item chronic Hepatitis B quality of life instrument (CHBQOL) using the modified Delphi method and Rasch model analysis, this study conducted a secondary data analysis on 578 chronic Hepatitis B (CHB) patients. The preliminary evaluation of the item's importance of the original CHBQOL and the final review of the short form of CHBQOL (CHBQOL-SF) were collected by the Delphi method. A bi-factor model was estimated and Rasch analysis with partial credit model was performed on each domain of the CHBQOL. Six items were suggested to remove based on the Delphi results. The fit of the bi-factor model was acceptable (RMSEA = 0.040; CFI = 0.983; TLI = 0.965). Disordered thresholds were initially found on three out of five items in Somatic symptoms, and four out of six items in Social stigma. Uniform differential item functioning was observed for three items for age group, two items for gender, and one item each for different ALT levels and HBV-DNA levels. Finally, the 10-item CHBQOL-SF retained the four-dimensional structure of the original instrument. The 10 items fit the Rasch model well and response options were set reasonably. The 10-item CHBQOL-SF would offer a brief and easily administrative CHB-specific patient-reported outcome measure for use in clinical practice and population studies.

Hepatitis B virus (HBV) is a major global health concern, with maternal-fetal transmission being the primary route of transmission, which can lead to chronic HBV infection in newborns. Long non-coding RNAs (lncRNAs) play crucial roles in gene regulation and immune responses, but their involvement in HBV transmission during pregnancy remains unclear. This study aimed to assess the impact of tenofovir disoproxil fumarate (TDF)-based antiviral therapy on lncRNA expression profiles and immune signaling pathways in umbilical cord blood and placental tissues and to identify potential therapeutic targets for preventing intrauterine HBV infection.

Umbilical cord serum and placental tissues were collected from six HBV carriers. Three carriers received TDF-based antiviral therapy, and the remaining carriers who did not receive antiviral therapy served as controls. LncRNA microarray analysis and bioinformatics were used to evaluate the effects of antiviral therapy on lncRNA expression profiles and signaling pathways.

Antiviral therapy exerted minimal effects on lncRNA expression profiles in umbilical cord blood. In placental tissues, significant alterations in lncRNA expression profiles were observed, including 249 upregulated and 381 downregulated lncRNAs. Antiviral therapy activated innate immune pathways, such as intracellular DNA sensing, chemokine signaling, type I interferon, Jak-Stat, and interferon-γ-mediated adaptive immunity. Through intersection analysis, CPED1 was found differentially expressed in both cord blood and placental tissues. KEGG pathway analysis suggested that low CPED1 expression may inhibit virus transmission via the JAK-STAT pathway.

This study demonstrated that TDF-based antiviral therapy altered lncRNA expression and activated immune signaling pathways in placental tissues, offering insights into the molecular mechanisms of maternal-fetal HBV transmission.

The costimulatory molecules OX40 and OX40L, members of the tumor necrosis factor (receptor) superfamily, play an important role in viral control through the activation of T cells. We speculate that activating the immune checkpoint OX40 may promote the inhibition of hepatitis B virus (HBV) replication.

To test this hypothesis, we investigated the expression dynamics of OX40/OX40L and studied the effects of activation of OX40 on HBV replication, and further explored the possible mechanism.

We found that the percentage of T cells expressing OX40 was lower in adult patients with chronic hepatitis B (CHB) than in healthy adults and was negatively correlated with serum viral load. In contrast, the percentage of B cells and monocytes expressing OX40L was increased in adult patients with CHB and positively correlated with liver inflammatory indicators. The expression of OX40 in T cells and OX40L in monocytes was positively correlated with age in healthy donors. In addition, the levels of serum HBsAg and intrahepatic HBV DNA decreased in an HBV mouse model with an agonistic antibody that activates OX40. This viral inhibition process coincides with changes in liver inflammation, the ratio of T cell subsets, and T cell-related cytokines. Finally, we found that the OX40 activation-mediated inhibition of HBV replication was more dependent on CD8+ T cells than on CD4+ T cells.

The expression levels of the immune checkpoints OX40/OX40L in adult patients with CHB are closely related to virus clearance. The activation of OX40 can suppress HBV replication through a mechanism that is more dependent on CD8+ T cells than on CD4+ T cells. Thus, OX40 is a promising therapeutic target for the treatment of CHB.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are significant global health challenges, leading to severe complications such as liver cirrhosis and hepatocellular carcinoma. Despite available vaccines and treatments, these infections persist, particularly, in regions such as Iraq. This study aimed to assess the prevalence of HBV and HCV among couples attending premarital screening programs in Zakho, Kurdistan Region of Iraq and explore the associated demographic risk factors.

A retrospective cross-sectional study was conducted from October 1, 2019 to December 31, 2023, including 15,091 couples. Laboratory screening for HBV and HCV was performed using enzyme-linked immunosorbent assay, followed by RNA quantification for HCV-positive cases.

Of the total of 15,091 couples, the overall prevalence of HBV was 0.92% and HCV was 0.07%. Males, individuals aged 23-31 years, and urban residents had higher infection rates. Significant risk factors included age 23-31 years, male gender, and urban residency (P <0.05).

The prevalence of HBV and HCV among couples in Zakho is consistent with regional data. Higher infection rates in males and urban areas suggest the need for targeted interventions, including public education and screening for high-risk populations.

Hepatitis B is a viral infection spread by contact with infected blood, semen, or other bodily fluids. The availability of a safe and effective vaccine has played a tremendous role in decreasing the prevalence of the disease since 1981. However, according to the Center for Disease Control, when adjusting for under-ascertainment and under-reporting, there were approximately 14,000 acute hepatitis B cases in the USA in 2020. There have been multiple outbreaks of vaccine-preventable disease in sports leagues including mumps and measles. However, there is limited literature available assessing hepatitis B prevalence of immunity in NCAA athletes.

Hepatitis B immunization data from local NCAA Division I and III athletes were analyzed from the years 2016-2023 through Epic chart review. The age range of the cohort was set at 18-24, upon time of evaluation. An Epic Reportwriter ran a SlicerDicer query searching for athletes who presented to our healthcare system clinic and/or training room facilities meeting the appropriate criteria outlined above. All NCAA sports were included. Data obtained included gender, race, country of birth, hepatitis B vaccination records, and hepatitis B surface antibodies if available.

We had a total of 379 athletes. The median age for the cohort was 20 years. Overall, 64.6% of the athletes had received the hepatitis B vaccine. Only 4 athletes (1.06%) had hepatitis B surface antibody results available in their chart. All 4 of those athletes had a negative titer.

A majority of the athletes in this study had completed their hepatitis B vaccination. While 64.6% of athletes were vaccinated, the healthcare system needs to do a better job addressing vaccine adherence and hesitancy to prevent future outbreaks.

The global strategy to eradicate Hepatitis B (HBV), Hepatitis C (HCV), and HIV by 2030 is critical due to their impact and challenges to healthcare systems. HCV is curable, but HBV and HIV are only suppressible, with a vaccine available solely for HBV. Innovative diagnostic methods are needed, especially for high-risk populations like people who inject drugs (PWID). This study validates a dried blood spot (DBS) nucleic acid amplification test (NAAT) using the Hologic Panther system for detecting HBV, HCV, and HIV. The method was used to screen among PWID in the Capital Region of Denmark. The DBS method demonstrated high sensitivity, with a 95 % limit of detection (LoD) of 2711 IU/mL for HBV, 525 IU/mL for HCV, and 4022 copies/mL for HIV. Screening of 83 PWID in Denmark revealed a 13 % prevalence of active HCV infection, offering significant benefits in settings where traditional venous access is difficult.

Accurate detection and monitoring of environmental pollutants are of paramount importance for disease prevention and public health. In recent years, the ever-expanding human activities and industrial production have given rise to a sharp increase in the complexity and variety of these pollutants, which pose significant threats to human well - being. Environmental pollutants stem from multiple sources, such as heavy metals, persistent organic pollutants, inorganic non - metallic pollutants, emerging pollutants, and biological contaminants. Traditional detection technologies, though valuable for their sensitivity and accuracy, are constrained by complex sample preparation, poor selectivity, and the absence of standardized detection methods. On the other hand, emerging technologies, including nanotechnology, molecular detection methods, biosensors, Surface-Enhanced Raman Spectroscopy (SERS), multi-omics, and big data analysis, offer promising solutions for rapid and sensitive pollutant detection. The establishment of environmental monitoring networks and data - sharing platforms further enhances real - time pollutant monitoring and provides solid data support for public health initiatives. Nonetheless, challenges persist, including data integration, exposure assessment, and the development of cost-effective and portable detection solutions. Future progress in interdisciplinary approaches and technology integration will be crucial for advancing environmental pollutant detection and facilitating comprehensive disease prevention. This review systematically classifies environmental pollutants and showcases the latest advancements in detection technologies, offering critical insights for environmental monitoring and public health protection.

The implementation of effective blood donation screening for hepatitis B virus (HBV) anti-core antibodies with highly sensitive molecular HBV DNA detection in low-endemic countries like the United Kingdom has improved blood safety. However, the linkage to care and management for blood donors with occult HBV infection (OBI) is a complex dilemma involving virological, clinical, methodological, and social issues. Limited evidence suggests that OBI may accelerate the progression of liver disease and cancer. The need for a specialist referral for donors identified with OBI carries mixed opinions from blood establishments, hepatologists, and public health. Following extensive multidisciplinary discussions, experts agree upon a need for clear messaging for donors and to consider the oncogenic implications of OBI. Proposals for future studies are identified, and the applicability of the recommendations in low-resource, high-endemic regions is considered, as well as the inclusion of OBI in global hepatitis elimination targets.

Entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide(TAF) are first-line nucleos(t)ide analogs (NUCs) with chronic hepatitis B (CHB). This study aimed to assess the renal safety profile in NUC-experienced CHB patients who received ETV, TDF or TAF therapy.

This retrospective observational cohort study investigated factors related to renal function in 154 patients with NUC-experienced CHB who received ETV, TDF, and TAF therapy for 48 weeks. Changes in UREA, uric acid (UA), creatinine (Cr), and estimated glomerular filtration rate (eGFR) were analyzed using a one-way analysis of variance. A linear mixed-effects model for repeated measures was used to evaluate the correlation between baseline information and eGFR changes 48 weeks following treatment initiation. The model considered sex, baseline age, viral load, aminotransferases, renal function, and treatment group as fixed effects, and incorporated random effects for individual subjects.

There were no significant differences in UA or Cr levels during therapy over time. The eGFR level was elevated in ETV-treated patients (117.5 ± 16.65 mL/min/1.7m2 vs 109.8 ± 15.69 mL/min/1.7m2, P=0.027), whereas it did not change significantly in TDF- (123.6 ± 28.54 mL/min/1.7m2 vs 115.5 ± 20.44 mL/min/1.7m2, P=0.070) and TAF-treated (121.6 ± 23.44 mL/min/1.7m2 vs 113.4 ± 16.90 mL/min/1.7m2, P=0.053) patients. Younger patients (<30 years) and those with higher HBV DNA (> 7 log10IU/mL) and lower alanine aminotransferase levels (<5 × upper limit of normal) showed a significant improvement in eGFR elevation during NUCs therapy. The linear mixed-effects model showed that the baseline HBV DNA level was an important positive predictor of eGFR elevation at 48 weeks following treatment initiation (estimate was 1.437 and 2.449, P<0.001).

In real-life experience, ETV, TDF, and TAF therapy may not be associated with eGFR changes in NUC-experienced CHB patients without baseline renal impairment.

Chronic infection with Clonorchis sinensis (C.sinensis) has been associated swith the development of intrahepatic cholangiocarcinoma (ICC); however, the relationship between C.sinensis and hepatocellular carcinoma (HCC) remains uncertain.

This study examined 120 patients with liver cancer in the clonorchiasis endemic area of Hengzhou, Guangxi, China. The type of cancer, the differentiation grade according to Edmondson Steiner's classification, and the pathological characteristics of HCC were determined through postoperative tissue biopsy. C.sinensis infection was detected by measuring serum specific IgG antibody, and hepatitis B virus (HBV) infection was determined by detecting serum HBsAg and HBV DNA in HCC tissues. The C.sinensis infection rates in control groups were drawn from the local general population based on previous surveys. The association between C.sinensis infection and HCC was analyzed by comparing the differences in C.sinensis infection rates between the two groups.

Of the patients evaluated, 98 (81.7%) had HCC, 21 (17.5%) had ICC, and 1 (0.8%) had comorbidity of HCC/ICC. Among the HCC patients, 24 (24.5%) were solely infected with HBV, 71 (72.4%) were C. sinensis seropositive, and 3 (3.1%) showed no evidence of infection. C. sinensis seropositive rates in HCC patients are much higher than in general outpatient and non-liver cancer inpatients (χ2 = 141.92, p < 0.001), as well as in the local residents (χ2 = 82.61/21.38, p < 0.001). There were no significant differences in the pathological type, differentiation grade, and lesion composition between the tumor associated with C.sinensis/HBV mono- and co-infection (p > 0.05). Among the patients with C.sinensis-related HCC, 8 (8.2%) were solely C.sinensis seropositive, while 63 (64.3%) were co-infected with HBV. Infection with C. sinensis and HBV has a significant impact on the pathological types of liver cancer (χ2 = 22.86, p < 0.001).

These findings indicate that HCC still accounts for the majority of liver cancer in this region. In addition to being most commonly related with HBV infection, HCC may also be related to C. sinensis infection. Co-infection of C. sinensis and HBV may enhance the development of HCC in this area.

Not applicable.

The effectiveness of the hepatitis E vaccine in high-risk groups, such as chronic hepatitis B (CHB) patients, remains understudied. A key clinical manifestation of CHB is the persistent positivity of hepatitis B surface antigen (HBsAg). We conducted a test-negative design study involving 2,926 HBsAg-positive individuals (born 1941-1991; median age 49.0; male-to-female ratio of 1.4), identified through a hepatitis surveillance system, as part of the phase 3 trial (NCT01014845) of the recombinant hepatitis E vaccine HEV 239 (Hecolin). This system monitored suspected hepatitis cases and performed diagnoses across 11 townships in Dongtai, Jiangsu, China, from 2007 to 2017. Vaccine effectiveness of HEV 239 was assessed by comparing vaccination status between confirmed 96 hepatitis E cases and 2830 test-negative controls, using logistic regression adjusted for sex and age. We found that HEV 239 vaccination was associated with a reduced risk of hepatitis E among HBsAg-positive individuals, with an estimated effectiveness of 72.1% [95% confidence interval (CI) 11.2-91.2], and 81.5% (95% CI 35.9-94.6) among phase 3 trial participants. Our findings show that HEV 239 is highly effective in HBsAg-positive adults, supporting its future recommended use in this population.

A causal mediation model with multiple time-to-event mediators is exemplified by the natural course of human disease marked by sequential milestones with a time-to-event nature. For example, from hepatitis B infection to death, patients may experience intermediate events such as liver cirrhosis and liver cancer. The sequential events of hepatitis, cirrhosis, cancer, and death are susceptible to right censoring; moreover, the latter events may preclude the former events. Casting the natural course of human diseases in the framework of causal mediation modeling, we establish a model with intermediate and terminal events as the mediators and outcomes, respectively. We define the interventional analog of path-specific effects (iPSEs) as the effect of an exposure on a terminal event mediated (or not mediated) by any combination of intermediate events without parametric models. The expression of a counting process-based counterfactual hazard is derived under the sequential ignorability assumption. We employ composite nonparametric likelihood estimation to obtain maximum likelihood estimators for the counterfactual hazard and iPSEs. Our proposed estimators achieve asymptotic unbiasedness, uniform consistency, and weak convergence. Applying the proposed method, we show that hepatitis B induced mortality is mostly mediated through liver cancer and/or cirrhosis whereas hepatitis C induced mortality may be through extrahepatic diseases.

To evaluate the therapeutic impact of reduced glutathione combined with entecavir on liver function, fibrosis, and HBV-DNA clearance in chronic hepatitis B patients.

This was a randomized controlled trial. This study included 90 patients diagnosed with chronic hepatitis B, who were randomly divided into two groups (observation group and control group) using a random number table, with 45 patients in each group. The control group received standard entecavir treatment (0.5 mg/time, once a day, continuous treatment for 3 months), while the observation group received a combination therapy of reduced glutathione and the standard entecavir treatment. Liver function markers (ALT, TBIL, AST, ALB), fibrosis markers (HA, PC III, LN), and liver fibrosis grades were assessed pre-and post-treatment. HBV-DNA negative conversion rates were recorded at 4, 12, 24, and 48 weeks. The incidence of adverse reactions, including nausea, vomiting, headache, and mild gastric discomfort, was recorded and compared between the two groups during the treatment period.

ALT decreased from 348.96 ± 31.47 U/L to 31.11 ± 9.78 U/L in the observation group and from 347.90 ± 31.40 U/L to 56.90 ± 16.32 U/L in the control group (P < 0.05). TBIL decreased from 61.78 ± 4.94 µmol/L to 18.82 ± 2.93 µmol/L in the observation group and from 61.32 ± 4.93 µmol/L to 26.70 ± 4.44 µmol/L in the control group (P < 0.05). ALB increased from 29.65 ± 0.94 g/L to 48.76 ± 4.85 g/L in the observation group and from 29.77 ± 0.90 g/L to 34.12 ± 0.84 g/L in the control group (P < 0.05). The observation group showed greater reductions in HA, PC III, and LN, and improved liver fibrosis grades (P < 0.05). HBV-DNA negative conversion rates in the observation group were 15.56%, 35.56%, 60.00%, and 68.89% at 4, 12, 24, and 48 weeks, respectively, compared to 2.22%, 6.67%, 17.78%, and 42.22% in the control group (P < 0.05). Adverse reaction rates were 8.89% in the observation group and 20.00% in the control group (P > 0.05).

Reduced glutathione combined with entecavir significantly improves liver function, reduces liver fibrosis, and enhances HBV-DNA clearance in chronic hepatitis B patients without increasing adverse reactions.

This study assessed the impact of chronic hepatitis B virus (HBV) infection on ovarian reserve in women.

We analyzed data from 38,861 infertile women undergoing their first in vitro fertilization (IVF) treatment (2016-2022), including 1574 HBsAg-positive cases. A control group of 1574 HBsAg-negative women was matched by age and body mass index (BMI). Comparison of clinical characteristics, antral follicle count (AFC), follicle-stimulating hormone (FSH), luteinizing hormone (LH)/FSH ratio, anti-Müllerian hormone (AMH), gonadotropins (Gn) days, total Gn dosage, number of retrieved oocytes, number of mature metaphase II (MII) oocytes, and the proportion of patients with diminished ovarian reserve (DOR; AMH < 1.1 ng/ml) between two groups.

HBsAg-positive women showed lower basal AFC and AMH, higher basal FSH, received more Gn, and had fewer retrieved and MII oocytes than HBsAg-negative women. No significant differences in ovarian reserve or stimulation outcomes were found between e antigen-positive and e antigen-negative HBV-infected groups. DOR was less prevalent in HBsAg-negative women, and logistic regression indicated a higher DOR risk with HBV infection.

HBsAg positivity significantly impairs ovarian reserve in women, but e antigen status does not notably affect it among HBV-infected individuals.

Changes in serum hepatitis B surface antigen (HBsAg) during treatment are associated with HBsAg loss. However, little is known about the trajectory patterns of HBsAg in early treatment and their relationship to subsequent HBsAg loss.

A retrospective study was conducted on 166 treatment-naive children with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB). Latent class trajectory analysis was used to identify trajectory groups of serum HBsAg. Cox proportional hazards models were used to assess the association between HBsAg trajectory groups and HBsAg loss.

The median follow-up time was 20.70 (interquartile range, 12.54-34.17) months, and HBsAg loss occurred in 70 (42.17%) of all study participants. Using latent class trajectory analysis, HBeAg-positive patients with CHB were classified into 3 trajectory groups: trajectory 1 (sustained stability, 24.70%), trajectory 2 (slow decline, 38.55%), and trajectory 3 (rapid decline, 36.75%), respectively. The risk of achieving HBsAg loss was higher in both trajectory 2 (hazard ratio, 3.65 [95% confidence interval, 1.70-7.83]) and trajectory 3 (7.27 [3.01-17.61]), respectively.

Serum HBsAg levels during early treatment can be classified into distinct trajectory groups, which may serve as an additional predictive indicator for HBsAg loss in HBeAg-positive children with CHB.