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Flares after nucleos(t)ide analogue (NA) cessation are common and potentially harmful. Predictors of flares are required for risk stratification and to guide off-treatment follow-up. This multicenter cohort study included virally suppressed patients with chronic hepatitis B (CHB) who were hepatitis B e antigen negative at NA cessation. Hepatic flares were defined based on ALT levels of ≥5x, 10x or 20x the upper limit of normal (ULN). Multivariable Cox regression analyses were performed with censoring at retreatment, HBsAg loss or loss to follow-up. A sub-analysis was performed including HBV DNA levels within the first 12 weeks as a time-dependent covariate. Of the 1,552 included patients, 350 developed a flare (ALT ≥5x ULN), of whom 70.6% did within the first year. One-year cumulative incidences for ALT flares ≥5x, ≥10x, ≥20x ULN were 18.6%, 10.2% and 3.4%, respectively. Severity of flares decreased over time, but severe flares still occurred after 1 year. Thirteen patients decompensated after a flare, of whom three died. Flares did not seem to be associated with increased rates of HBsAg loss (adjusted hazard ratio [aHR] 1.42, p = 0.28). Multivariable analyses showed that older age (aHR 1.02, p = 0.001), male sex (aHR 1.57, p = 0.003), HBsAg levels at NA withdrawal (100-1,000 IU/ml; aHR 1.99, p < 0.001; >1,000 IU/ml; aHR 2.65, p < 0.001) and tenofovir disoproxil fumarate vs. entecavir therapy (aHR 2.99, p < 0.001) were predictive of flares (≥5x ULN). Early HBV DNA levels >5log 10 IU/ml were associated with the highest risk of flares (aHR 2.36, p < 0.001). Flares are common after NA withdrawal, especially within the first year and can result in hepatic decompensation and death. Older age, male sex, higher HBsAg levels at end of treatment and tenofovir therapy were associated with a higher risk of flares. Close monitoring and retreatment should be considered if HBV DNA levels exceed 5log 10 IU/ml within the first 12 weeks. This is the first large global multi-centered cohort study which provides detailed data about flares after nucleos(t)ide analogue cessation in patients with chronic hepatitis B. Older age, male sex, higher HBsAg levels at end of treatment and tenofovir therapy were associated with a higher risk of flares. These results could guide follow-up after withdrawal, helping clinicians identify high-risk patients and decide when to restart anti-viral therapy, which we recommend if HBV DNA levels exceed 5log 10 IU/ml within the first 12 weeks. not applicable. [Display omitted] • Flares are common after NA cessation (5 year: 33%) and can still occur after 1 year. • These flares do not increase HBsAg loss and should be considered undesirable events. • HBsAg ≥100 IU/ml at end of therapy, TDF and male sex were associated with increased flare risk. • Retreat if (early) HBV DNA levels exceed 5log 10 IU/ml. [ABSTRACT FROM AUTHOR]

Background: The function of CD69 expressed on T cells in chronic hepatitis B (CHB) remains unclear. We aimed to elucidate the roles of CD69 on T cells in the disease process and in antiviral therapy for CHB. Methods: We enrolled 335 treatment-naive patients with CHB and 93 patients with CHB on antiviral therapy. CD69, antiviral cytokine production by T cells, T-helper (Th) cells, and inhibitory molecules of T cells were measured using flow cytometry, and clinical-virological characteristics were examined dynamically during antiviral therapy. Results: CD69 expression on CD3+, CD4+, and CD8+ T cells was the lowest in the immune-active phase and was negatively correlated with liver transaminase activity, fibrosis features, inflammatory cytokine production by T cells, and Th-cell frequencies but positively with inhibitory molecules on T cells. CD69 expression on CD3+, CD4+, and CD8+ T cells decreased after 48 weeks of antiviral therapy, and patients with hepatitis B e antigen (HBeAg) seroconversion in week 48 showed lower CD69 expression on T cells at baseline and week 48. The area under the ROC curve of CD69 expression on T cells at baseline for predicting HBeAg seroconversion in week 48 was 0.870, the sensitivity was 0.909, and the specificity was 0.714 (P =0.002). Conclusions: CD69 negatively regulates T-cell immunity during CHB, and its expression decreases with antiviral therapy. CD69 expression predicts HBeAg seroconversion in week 48. CD69 may play an important negative role in regulating T cells and affect the efficacy of antiviral therapy. [ABSTRACT FROM AUTHOR]

Background: The coexistence of viral hepatitis with diabetes mellitus (DM) significantly escalates the risk of severe outcomes. This study aimed to determine the seroprevalence and associated factors of hepatitis B (HBV) and hepatitis C (HCV) viral infections among DM patients in northern Tanzania. Materials and methods: Conducted between February 2023 and May 2023, this hospital-based cross-sectional study enrolled 189 patients with DM from the Diabetic Clinic of Kilimanjaro Christian Medical Centre. A structured questionnaire captured relevant clinical information, and plasma blood sample was assessed for hepatitis B surface antigen and anti-hepatitis C antibody seropositivity. Data analysis employed SPSS v26, and a chi-square test was used to determine the statistical difference of HBV and HCV among patients with DM. Logistic regression was performed to determine factors associated with HBV and HCV. Results: Among the 189 patients with DM, the seroprevalence of HBV and HCV infections stood at 2.1% and 0.5%, respectively. Males constituted a significant majority (80%) of those affected by viral hepatitis. Furthermore, 60% of affected patients were in non-union relationships (single, widowed, or divorced), and 40% reported multiple sexual partners. However, the study found no significant association between traditional associated factors and viral infection acquisition. Conclusion: The study's findings reveal a relatively low prevalence of HBV and HCV infections among patients with DM compared to the general population, with no significant association among factors. Nonetheless, the results underscore the importance of early screening and vaccination for HBV and HCV in patients with DM. Such efforts are crucial for curbing infection spread and reducing the risk of hepatocellular carcinoma development in this vulnerable population. [ABSTRACT FROM AUTHOR]

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. Effectiveness of the hepatitis E vaccine HEV 239 amongst high-risk groups isn't well studied. Here, Zhuang et al. analyse a decade of surveillance data (2007–2017) from Dongtai, China, and estimate HEV 239 effectiveness of 72% amongst hepatitis B virus infected people. [ABSTRACT FROM AUTHOR]

Background: In Ethiopia, hepatitis B virus infections are prevalent and highly endemic. Additionally, there has been a significant increase in hospital admissions, morbidity, and mortality associated with hepatitis B virus infections. This study aimed to assess the prevalence of hepatitis B virus infection and associated factors among adult intrafamilial household contacts of pregnant women index cases attending antenatal care clinics in the central Ethiopian region. Methods: A community-based cross-sectional study was conducted between October 1, 2023, and March 1, 2024. Three hundred eighty-five adult intrafamilial household contacts were randomly selected via lottery methods. A 3 ml venous blood sample was taken from adult intrafamilial household contacts and checked for hepatitis B virus infection through hepatitis B surface antigen. An interviewer-administered questionnaire was used to collect the data. A logistic regression model predicted the relationship between predictor and outcome variables. A p-value of < 0.05 indicated statistical significance. Results: The overall response rate was 96.1%. Two-thirds of the adults of intrafamilial household contacts (n = 229; 61.9%) were aged between 18 and 28 years, with a mean age of 28 years. The prevalence rate of hepatitis B virus infection among adults of intrafamilial household contacts with pregnant women as the index case was 11.6% (95% CI, 8.6 to 15.1). Being male (AOR: 0.09; 95% CI: 0.03, 0.37) and a duration of stay with the index case of less than six months (AOR: 0.30; 95% CI: 0.11, 0.81) were associated with a reduced risk of hepatitis B virus infection. Meanwhile, large family sizes (≥ 7) (AOR: 4.32; 95% CI: 1.34, 13.98), genital discharge (AOR: 3.14; 95% CI: 1.60, 6.15), engagement in unsafe sex (AOR: 2.37; 95% CI: 1.13, 4.97), and a history of mortality due to hepatitis in the family (AOR: 3.03; 95% CI: 1.09, 8.42) were associated with an increased risk of hepatitis B virus infection. Conclusion: This study found that hepatitis B surface antigen seropositivity among adult intrafamilial household contacts with pregnant women index cases in the central Ethiopia region was high at 11.6%. These findings suggest that interventions to prevent HBV infection should prioritize educational campaigns targeting adult intrafamilial household contacts of HBV-positive index cases, focusing on risk factors associated with HBV transmission, prevention, counselling, testing, and vaccination. [ABSTRACT FROM AUTHOR]

Background: The problem caused by viral hepatitis is a major public health challenge faced in the past decade, and the global goal of eliminating viral hepatitis by 2030 is still far away. With the use of hepatitis B vaccine and the launch of new drugs, there are more means to control viral hepatitis and more technologies to prevent, diagnose and treat it. While improving the coverage of vaccine use, drugs for treating hepatitis B are not only becoming more effective, but also decreasing in price. The objective of this article was to explore the urgent issues that need to be addressed in global viral hepatitis with the increasing availability of vaccines and antiviral drugs. Main text: The updated World Health Organization guidelines for the prevention, diagnosis, care and treatment for people with chronic hepatitis B infection (2024 edition) and Chinese guidelines for the prevention and treatment of chronic hepatitis B (version 2022) simplify clinical algorithms for the diagnosis, treatment, and monitoring of hepatitis B, expand treatment eligibility criteria, and provide alternative treatment options, which will cover a higher proportion of all hepatitis B surface antigen positive populations. These actions promote the global goal of eliminating the public health hazards of viral hepatitis by 2030. Among the countries that have made remarkable progress in eliminating viral hepatitis policies, the key strategy is to simplify the diagnosis and treatment plan. Furthermore, the World Health Organization has identified 38 priority countries for viral hepatitis. Expand access to viral hepatitis services in these countries. Conclusions: Regions and countries with the high burden of viral hepatitis still need to take urgent action regarding the new measures proposed by the WHO to achieve the 2030 targets. First, countries must establish a complete public health system aligned with the World Health Organization's strategy. Second, provide effective, people-oriented services and public prevention strategies. Third, prioritize the implementation of health strategies in the 38 identified priority countries. Finally, use complete and measurable data to monitor progress. [ABSTRACT FROM AUTHOR]

Background: As an uncommon serological pattern, the effect of hepatitis B e antigen/anti-hepatitis B e (HBeAg/anti-HBe) coexistence on peginterferon-α (Peg-IFN-α) therapy in patients with chronic hepatitis B (CHB) remains unknown. Moreover, Peg-IFN-α is clinically limited due to several side effects. It is of significant value to early identify the favored population for Peg-IFN-α therapy in CHB patients. Objectives: This study aimed to analyze the impact of HBeAg/anti-HBe coexistence on the effectiveness of Peg-IFN-α and to construct a nomogram for predicting the occurrence of HBeAg seroconversion in treatment-naïve CHB patients with Peg-IFN-α therapy. Design: Retrospective, case–control study of treatment-naïve CHB patients with Peg-IFN-α at a tertiary care center. Methods: Data from HBeAg-positive treatment-naïve CHB patients were retrospectively analyzed. Clinical characteristics of the HBeAg/anti-HBe coexistence group were compared with those of the anti-HBe-negative group. In addition, univariate and multivariate logistic regression analyses were performed to identify independent risk factors for HBeAg seroconversion. The nomogram for the prediction of HBeAg seroconversion was constructed and evaluated. Results: A total of 140 HBeAg-positive CHB patients were enrolled. Patients with HBeAg/anti-HBe coexistence accounted for 11.4% of HBeAg-positive patients, and their hepatitis B surface antigen (HBsAg) and HBeAg levels were significantly lower than those of anti-HBe negative patients, but the HBeAg seroconversion rate was higher after Peg-IFN-α treatment. As revealed by multivariate logistic analysis, HBeAg/anti-HBe coexistence, baseline HBsAg, baseline HBeAg, and alanine aminotransferase ratio at baseline were independent correlates of HBeAg seroconversion. The nomogram model constructed based on these four independent correlates demonstrated good discrimination (area under the curve = 0.866), calibration, and clinical adaptability. Conclusion: HBeAg/anti-HBe coexistence is associated with a higher HBeAg seroconversion rate, and the nomogram model constructed based on HBeAg/anti-HBe coexistence performs well in predicting HBeAg seroconversion in treatment-naïve CHB patients treated with Peg-IFN-α therapy. [ABSTRACT FROM AUTHOR]

Current treatments for hepatitis B virus (HBV), such as interferons and nucleic acid analogs, have limitations due to side effects like depression and the development of drug-resistant mutants, highlighting the need for new therapeutic approaches. In this study, we identified microRNA-3145 (miR-3145) as a host-derived miRNA with antiviral activity that is upregulated in primary hepatocytes during HBV infection. The expression of its precursor, pri-miR-3145, increased in response to the the virus infection, and miR-3145 downregulated the hepatitis B virus S (HBS) antigen and hepatitis B virus X (HBX), thereby inhibiting viral replication. The binding site for miR-3145 was located in the HBV polymerase (pol) region, as experimentally confirmed. Moreover, overexpression of HBS and HBX induced pri-miR-3145 expression through endoplasmic reticulum stress. The expression of pri-miR-3145 showed a strong correlation with the Nance–Horan syndrome-like 1 (NHSL1) gene, as it is encoded within an intron of NHSL1, and higher NHSL1 expression in hepatocellular carcinoma patients with HBV infection was associated with better prognosis. These findings suggest that miR-3145-3p, along with small molecules targeting its binding sites, holds promise as a potential therapeutic candidate for HBV treatment. [ABSTRACT FROM AUTHOR]

Key Points: Question: In pregnant individuals with hepatitis B virus (HBV) and high viremia, is initiation of tenofovir disoproxil fumarate (TDF) at gestational week 16 combined with HBV vaccinations of infants noninferior to initiation of TDF at week 28 combined with HBV vaccinations and HBV immune globulin (HBIG) in preventing mother-to-child transmission? Findings: Initiating maternal TDF therapy at week 16 combined with HBV vaccinations for infants was noninferior to initiating maternal TDF therapy at week 28 combined with HBIG and HBV vaccinations for infants in preventing mother-to-child transmission of HBV (0.76% [1/131] vs 0% [0/142]). Meaning: TDF therapy at gestational week 16 combined with HBV vaccinations of infants avoided the need for HBIG and was noninferior to standard care for preventing HBV transmission from pregnant women to infants. Importance: Standard care for preventing mother-to-child transmission (MTCT) of hepatitis B virus (HBV) in highly viremic mothers consists of maternal antiviral prophylaxis beginning at gestational week 28 combined with an HBV vaccine series and HBV immune globulin (HBIG) at birth. However, HBIG is unavailable in some resource-limited areas. Objective: To determine whether initiating tenofovir disoproxil fumarate (TDF) at gestational week 16 combined with HBV vaccinations for infants is noninferior to the standard care of TDF at gestational week 28 combined with HBV vaccinations and HBIG for infants in preventing MTCT in mothers with HBV and high levels of viremia. Design, Setting, and Participants: An unblinded, 2-group, randomized, noninferiority clinical trial was conducted in 7 tertiary care hospitals in China. A total of 280 pregnant individuals (who all identified as women) with HBV DNA levels greater than 200 000 IU/mL were enrolled between June 4, 2018, and February 8, 2021. The final follow-up occurred on March 1, 2022. Interventions: Pregnant individuals were randomly assigned to receive either TDF starting at gestational week 16 with HBV vaccinations for the infant or TDF starting at gestational week 28 with HBV vaccinations and HBIG administered to the infant. Main Outcomes and Measures: The primary outcome was the MTCT rate, defined as detectable HBV DNA greater than 20 IU/mL or hepatitis B surface antigen positivity in infants at age 28 weeks. Noninferiority was established if the MTCT rate in the experimental group did not increase by more than an absolute difference of 3% compared with the standard care group, as measured by the upper limit of the 2-sided 90% CI. Results: Among 280 pregnant individuals who enrolled in the trial (mean age, 28 years; mean gestational age at enrollment, 16 weeks), 265 (95%) completed the study. Among all live-born infants, using the last observation carried forward, the MTCT rate was 0.76% (1/131) in the experimental group and 0% (0/142) in the standard care group. In the per-protocol analysis, the MTCT rate was 0% (0/124) in the experimental group and 0% (0/141) in the standard care group. The between-group difference was 0.76% (upper limit of the 2-sided 90% CI, 1.74%) in all live-born infants and 0% (upper limit of the 2-sided 90% CI, 1.43%) in the per-protocol analysis. Both comparisons met the criterion for noninferiority. Rates of congenital defects and malformations were 2.3% (3/131) in the experimental group and 6.3% (9/142) in the standard care group (difference, 4% [2-sided 95% CI, −8.8% to 0.7%]). Conclusions and Relevance: Among pregnant women with HBV and high levels of viremia, TDF beginning at gestational week 16 combined with HBV vaccination for infants was noninferior to the standard care of TDF beginning at gestational week 28 combined with HBIG and HBV vaccination for infants. These results support beginning TDF at gestational week 16 combined with infant HBV vaccine to prevent MTCT of HBV in geographic areas where HBIG is not available. Trial Registration: ClinicalTrials.gov Identifier: NCT03476083 This noninferiority randomized clinical trial investigates whether administering tenofovir to pregnant individuals with hepatitis B virus beginning at gestational week 16 is noninferior to administering tenofovir beginning at gestational week 28 in preventing mother-to-child transmission. [ABSTRACT FROM AUTHOR]

Background: This study assessed the impact of chronic hepatitis B virus (HBV) infection on ovarian reserve in women. Methods: 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. Results: 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. Conclusions: HBsAg positivity significantly impairs ovarian reserve in women, but e antigen status does not notably affect it among HBV-infected individuals. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency of hepatitis b surface antigen (HBsAg) positivity and associated risk factors among children screened before surgical procedures. Study Design: Cross-sectional study. Setting: Department of Pediatric Medicine, National Institute of Child Health (NICH), Karachi, Pakistan. Period: 1st February 2024 to 30th July 2024. Methods: A total of 188 children of either gender, aged between 3 months to 15 years, and admitted for any surgical procedure were screened. Demographic information like gender, age, and weight were noted. Information regarding risk factors of HBV infection included evaluation of vaccination status, history of hospital admission, history of injection, blood transfusion, surgical procedure, body piercing, and family history of HBV. HBV infection was labeled on the basis of the presence of surface antigen tested using ELISA. Results: In 188 children, 122 (64.9%) were male, and the mean age was 7.23±7.00 years. HBsAg was positive in 57 (30.3%) children. HBsAg seropositivity was significantly associated with female gender (p=0.001), higher mean age (p=0.001), and higher mean weight (p<0.001). Absence of HBV vaccination (p<0.001), history of hospitalization (45.6% vs. 30.5%; p=0.046), injections (19.3% vs. 8.4%; p=0.033), blood transfusions (31.6% vs. 9.9%; p<0.001), family history of HBV (p=0.015), maternal HBV positivity (p<0.001), and body piercing (33.3% vs. 13.0%; p=0.001) were significantly associated with HBsAg positivity. Conclusion: The frequency of HBsAg positivity among children undergoing surgical procedures was high. Key risk factors associated with HBV seropositivity included absence of vaccination, maternal HBV positivity, family history of HBV, blood transfusions, hospital admissions, and body piercing. [ABSTRACT FROM AUTHOR]

The interaction of lipopolysaccharide with a recombinant protein is a serious bottleneck, particularly in the purification step of bioprocessing. Recombinant hepatitis B surface antigen (rHBsAg), the active ingredient of the hepatitis B vaccine, is probably contaminated by extrinsic LPS like other biopharmaceuticals. This research intends to eliminate LPS from its mixture with rHBsAg efficiently. Immobilized polymyxin B on magnetic nanoparticles (PMB-MNPs) was synthesized and implemented as an enhanced LPS affinity adsorbent (LAA). The 20–80 EU/dose binary samples with and without surfactant were applied to PMB-MNPs. Formerly, dynamic light scattering (DLS) and transmission electron microscopy (TEM) were examined on the samples to qualitatively show the dissociation effect of the surfactant. Considering the high potential interaction of LPS with HBsAg, the dissociation effects of 0.5 and 1.5% Tween 20 on the binary samples were assessed using immunoaffinity chromatography (IAC) as a quantification tool. The dissociation effect of Tween 20 substantially diminished the interaction, leading to a proportional increase of free LPS up to 66%. The synergetic effect of Tween 20 and privileged LAA was highly effective in eliminating more than 80% of LPS with a remarkable LPS clearance factor of 5.8 and a substantial protein recovery rate of 97%. [ABSTRACT FROM AUTHOR]

The risk of hepatocellular carcinoma (HCC) and hepatic decompensation persists after hepatitis B surface antigen (HBsAg) seroclearance. This study aimed to develop and validate a machine learning model to predict the risk of liver-related outcomes (LROs) following HBsAg seroclearance. A total of 4,787 consecutive patients who achieved HBsAg seroclearance between 2000 and 2022 were enrolled from six centers in South Korea and a territory-wide database in Hong Kong, comprising the training (n = 944), internal validation (n = 1,102), and external validation (n = 2,741) cohorts. Three machine learning-based models were developed and compared in each cohort. The primary outcome was the development of any LRO, including HCC, decompensation, and liver-related death. During a median follow-up of 55.2 (IQR 30.1–92.3) months, 123 LROs were confirmed (1.1%/person-year) in the Korean cohort. The model with the best predictive performance in the training cohort was selected as the final model (designated as PLAN-B-CURE), which was constructed using a gradient boosting algorithm and seven variables (age, sex, diabetes, alcohol consumption, cirrhosis, albumin, and platelet count). Compared to previous HCC prediction models, PLAN-B-CURE showed significantly superior accuracy in the training cohort (c-index: 0.82 vs. 0.63–0.70, all p <0.001; area under the receiver-operating characteristic curve: 0.86 vs. 0.62–0.72, all p <0.01; area under the precision-recall curve: 0.53 vs. 0.13–0.29, all p <0.01). PLAN-B-CURE showed a reliable calibration function (Hosmer–Lemeshow test p >0.05) and these results were reproduced in the internal and external validation cohorts. This novel machine learning model consisting of seven variables provides reliable risk prediction of LROs after HBsAg seroclearance that can be used for personalized surveillance. Using large-scale multinational data, we developed a machine learning model to predict the risk of liver-related outcomes (i.e., hepatocellular carcinoma, decompensation, and liver-related death) after the functional cure of chronic hepatitis B (CHB). The new model named PLAN-B-CURE was constructed using seven variables (age, sex, alcohol consumption, diabetes, cirrhosis, serum albumin, and platelet count) and a gradient boosting machine algorithm, and it demonstrated significantly better predictive accuracy than previous models in both the training and validation cohorts. The inclusion of diabetes and significant alcohol intake as model inputs suggests the importance of metabolic risk factor management after the functional cure of CHB. Using seven readily available clinical factors, PLAN-B-CURE, the first machine learning-based model for risk prediction after the functional cure of CHB, may serve as a basis for individualized risk stratification. [Display omitted] • A new machine learning model was developed to predict the risk of liver-related outcomes after the functional cure of CHB. • PLAN-B-CURE incorporated 7 variables: age, sex, alcohol consumption, diabetes, cirrhosis, serum albumin, and platelet count. • PLAN-B-CURE demonstrated significantly superior predictive accuracy to previous models in both training and validation cohorts. • PLAN-B-CURE low-risk group showed a significantly lower 5-year incidence of liver-related outcomes than the other groups. [ABSTRACT FROM AUTHOR]

Bepirovirsen, an antisense oligonucleotide, induces sustained reductions in hepatitis B surface antigen (HBsAg) and HBV DNA to below the lower limit of quantification (

Nucleo(s)tide analogue (NUC) cessation can lead to hepatitis B surface antigen (HBsAg) clearance but also a high rate of virological relapse. However, the effect of pegylated interferon alpha-2a (PegIFN-α-2a) on virological relapse after NUC cessation is unknown. Therefore, this study aimed to evaluate the effect of switching from NUC to PegIFN-α-2a treatment for 48 weeks on virological relapse up to week 96. In this multicenter randomized-controlled clinical trial, 180 non-cirrhotic patients with HBeAg-negative chronic hepatitis B on continuous NUC therapy for ≥2.5 years, with HBV DNA levels <60 IU/ml, were randomized to discontinue NUC therapy (n = 90) or receive 48 weeks of PegIFN-α-2a treatment (n = 90). Patients were followed up for up to 96 weeks. The primary endpoint was the virological relapse rate up to week 96. Intention-to-treat analysis revealed patients in the interferon monotherapy group had significantly lower cumulative virological relapse rates than the NUC cessation group until week 96 (20.8% vs. 53.6%, p <0.0001). Consistently, a significantly lower proportion of patients in the interferon monotherapy group had virological relapse than those in the NUC cessation group at 48 weeks off treatment (17.8% vs. 36.7%, p = 0.007). The virological relapse rate positively correlated with HBsAg levels in the NUC cessation group. The interferon monotherapy group had a lower cumulative clinical relapse rate (7.8% vs. 20.9%, p = 0.008) and a higher HBsAg loss rate (21.5% vs. 9.0%, p = 0.03) than the NUC cessation group. Switching from NUC to PegIFN-α-2a treatment for 48 weeks significantly reduces virological relapse rates and leads to higher HBsAg loss rates than NUC treatment cessation alone in patients with HBeAg-negative chronic hepatitis B. Nucleo(s)tide analogue (NUC) cessation can lead to HBsAg clearance but also a high rate of virological relapse, but an optimized scheme to reduce the virological relapse rate after NUC withdrawal is yet to be reported. This randomized-controlled trial investigated the effect of switching from NUC to PegIFN-α-2a treatment for 48 weeks on virological relapse up to week 96 in patients with HBeAg-negative chronic hepatitis B. The interferon monotherapy group had a significantly lower cumulative virological relapse rate (20.8% vs. 53.6%, p <0.0001) and higher HBsAg loss rate (21.5% vs. 9.0%, p = 0.03) than the NUC cessation group up to week 96. This provides an optimized strategy for NUC cessation in HBeAg-negative patients. NCT02594293. [Display omitted] • Switching to PegIFN-α reduces virological relapse and increases HBsAg loss after NUC cessation in HBeAg(-) patients. • HBeAg(-) patients with HBsAg <10 IU/ml have a high likelihood of HBsAg clearance when switching from NUCs to PegIFN-α. • Discontinuation is not appropriate in patients with HBsAg >1,000 IU/ml due to high relapse rate and poor HBsAg clearance. • It is safe to switch from NUCs to PegIFN-α in HBeAg(-) patients without significant fibrosis or cirrhosis. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) infection is associated with hepatitis, often progressing to liver cirrhosis or cancer, posing a significant public health challenge, particularly in Thailand. Previous research revealed that viral causes account for 18.5% of acute undifferentiated febrile illness (AUFI) in Asian countries. This study examined the prevalence of HBV and its seroprevalence among patients with AUFI at Tha Song Yang Hospital (Tak Province, Thailand). Methods: A cross-sectional study was conducted using residual serum samples collected between 2016 and 2017 from patients exhibiting symptoms of AUFI at Tha Song Yang Hospital. DNA was extracted and identified for HBV using real-time polymerase chain reaction (PCR). Positive samples were further characterized for the HBV genotype using semi-nested PCR targeting the pre-S gene. The serum samples were subjected to enzyme-linked immunosorbent assay to detect antibodies against hepatitis B core antigen (HBcAg) and hepatitis B surface antigen (HBsAg). Results: Among AUFI patients, the prevalence of HBV infection was 6.45% (18 of 279). Genotyping revealed the presence of genotype C with subgenotype C1 (88.89%) and genotype B with subgenotype B3 (11.11%). The seroprevalence of HBcAb and HBsAb was observed in 40.58% (112 of 276) and 48.98% (120 of 245) of the cases, respectively. Conclusions: The detection of HBV infection among AUFI patients (6.45%) underscores the spread of HBV within neighboring countries, such as Thailand and Myanmar. Pending confirmation of test results, physicians should maintain vigilance regarding potential HBV infection in AUFI cases. The overall seroprevalence showed 40.58% positivity for HBcAb and 48.98% for HBsAb. Therefore, individuals residing near the Thai border who did not receive the HBV vaccine at birth were recommended to complete a catch-up vaccination series of three doses to mitigate the HBV infection rate and enhance HBV antibody levels. [ABSTRACT FROM AUTHOR]

Key Points: Question: Does vaccination with a hepatitis B vaccine with a cytosine phosphoguanine adjuvant (HepB-CpG vaccine) improve hepatitis B virus (HBV) seroprotection in people with HIV and nonresponse to prior hepatitis B vaccine? Findings: In this open-label randomized clinical trial that included 561 people with HIV, 93% achieved HBV seroprotection with 2 doses of HepB-CpG vaccine and 99% achieved HBV seroprotection with 3 doses of HepB-CpG vaccine vs 81% with 3 doses of conventional hepatitis B vaccine with an aluminum hydroxide adjuvant. Meaning: A superior response was achieved in people with HIV and nonresponse to prior hepatitis B vaccination who received 2 or 3 doses of HepB-CpG vaccine. Importance: Nonresponse to hepatitis B vaccine is common among people with HIV, resulting in vulnerability to infection with hepatitis B virus (HBV). Objective: To compare the seroprotection response achieved with a 2-dose (noninferiority, 10% margin) and a 3-dose hepatitis B vaccine with a cytosine phosphoguanine adjuvant (HepB-CpG vaccine) vs a conventional 3-dose hepatitis B vaccine with an aluminum hydroxide adjuvant (HepB-alum vaccine) in people with HIV and prior nonresponse to HepB-alum vaccine. Design, Setting, and Participants: This phase 3, open-label, randomized clinical trial included people with HIV receiving antiretroviral therapy (CD4 cell count ≥100 cells/μL and HIV RNA <1000 copies/mL) without past or present serological evidence of having HBV or a response to hepatitis B vaccine. From December 2020 to February 2023, 561 adults were enrolled in the study at 41 sites in 10 countries in Africa, Asia, North America, and South America with follow-up for the primary outcome analysis through September 4, 2023. Interventions: Participants were randomly assigned to receive 2 doses of HepB-CpG vaccine administered intramuscularly at weeks 0 and 4; 3 doses of HepB-CpG vaccine administered intramuscularly at weeks 0, 4, and 24; or 3 doses of HepB-alum vaccine administered intramuscularly at weeks 0, 4, and 24. Main Outcomes and Measures: The primary outcome was a seroprotection response to hepatitis B vaccine (defined as level of antibody titer against hepatitis B surface antigen [HBsAg] ≥10 mIU/mL) at week 12 for the 2-dose regimen (8 weeks after dose 2) and at week 28 for 3-dose regimens (4 weeks after dose 3). Key secondary outcomes included seroprotection response at additional time points, antibody titer against HBsAg, and adverse events within 4 weeks of hepatitis B vaccination. Results: Of 561 participants included in the analysis (median age, 46 years [IQR, 31-56 years]); 64% were male; 17% of participants were Asian, 42% were Black, and 35% were White), a seroprotection response was achieved in 93.1% who received 2 doses of HepB-CpG vaccine (n = 174), in 99.4% who received 3 doses of HepB-CpG vaccine (n = 169), and in 80.6% who received 3 doses of HepB-alum vaccine (n = 165). The stratified difference in seroprotection response between the 2-dose HepB-CpG vaccine group and the 3-dose HepB-alum vaccine group was 12.5% (97.5% CI, 4.1%-20.9%), achieving noninferiority and indicating superiority. The 3-dose HepB-CpG vaccine regimen was superior to the 3-dose HepB-alum vaccine regimen (stratified difference in seroprotection response, 18.4% [repeated 97.5% CI, 10.4%-26.2%]). By week 12, more than 90% of participants who received HepB-CpG vaccine achieved a seroprotection response. The 3-dose regimen of HepB-CpG vaccine achieved a higher proportion of participants with antibody titer against HBsAg greater than 1000 mIU/mL (78.1%) vs the other 2 regimen groups (26.4% for 2 doses of HepB-CpG vaccine and 35.2% for 3 doses of HepB-alum vaccine). No unexpected safety issues were observed. Conclusions and Relevance: Among people with HIV and nonresponse to prior hepatitis B vaccination, both the 2-dose and 3-dose regimens of HepB-CpG vaccine achieved a superior seroprotection response compared with 3 doses of HepB-alum vaccine. Trial Registration: ClinicalTrials.gov Identifier: NCT04193189 This randomized clinical trial compares the seroprotection response achieved with a 2-dose and a 3-dose hepatitis B vaccine with a cytosine phosphoguanine adjuvant vs a conventional 3-dose hepatitis B vaccine with an aluminum hydroxide adjuvant in people with HIV and prior nonresponse to hepatitis B vaccine. [ABSTRACT FROM AUTHOR]

In recent years, the use of cationic peptides as alternative drugs with anticancer activity has received attention. In this study, the targeted release of curcumin (Cur) and CM11 peptide alone and together against hepatocellular carcinoma (HCC) was evaluated using chitosan nanoparticles (CS NPs) coated with Pres1 that target the SB3 antigen of HCC cells (PreS1-Cur-CM11-CS NPs). SB3 protein is the specific antigen of HCC and the PreS1 peptide is a part of the hepatitis B antigen, which can specifically bind to the SB3 protein. Chitosan was used to prepare NPs. To Cur and CM11 loading, drugs were added to the CS solution in appropriate concentrations. Pres1 was coupled to the surface of the NPs using EDC catalyst to target NPs against HepG2 cells. SEM and DLS analysis confirmed that the PreS1-Cur-CM11-CS NPs had a size of about 132 nm, the ideal size for penetrating the cell membrane. The loading of Cur and CM11 was equal to 87% and 65%, respectively, which had a sustained and better release in the acidic environment than in the physiological environment. The MTT assay showed that PreS1-Cur-CM11-CS NPs act in a targeted and specific manner with the highest toxicity on the HepG2 cells compared to the control by a decrease in viability of about 26% after 48 h based on cell apoptosis. The results showed that PreS1-Cur-CM11-CS NPs are capable of targeted and specific drug release against HepG2 cancer cells and have significant potential to fight this cancer. [ABSTRACT FROM AUTHOR]

Objective: Although pegylated interferon α-2b (PEG-IFN α-2b) therapy for chronic hepatitis B has received increasing attention, determining the optimal treatment course remains challenging. This research aimed to develop an efficient model for predicting interferon (IFN) treatment course. Methods: Patients with chronic hepatitis B, undergoing PEG-IFN α-2b monotherapy or combined with NAs (Nucleoside Analogs), were recruited from January 2018 to December 2023 at Tianjin Third Central Hospital. All patients achieved hepatitis B surface antigen (HBsAg) clearance post-treatment. Result: The study enrolled 176 patients with chronic hepatitis B, with the median IFN treatment course of 35.23 ± 25.22 weeks. They were randomly divided into two cohorts in a ratio of 7:3. And there were 123 patients in the training cohort and 53 patients in the validation cohort. Univariable and multivariable analyses demonstrated that baseline HBsAg, 12 weeks HBsAg and the presence of cirrhosis significantly influenced IFN treatment course, and both are risk factors (β=7.27,4.27,10.91; p<0.05). After adjusting for confounding factors, HBsAg remained a significant predictor (β=6.99, 95%CI: 3.59,10.40; p<0.05), which was finally included to establish the model. The actual and predicted values in the validation cohort were highly matched, meanwhile the mean absolute percentage error (MAPE), root mean square error (RMSE) and accuracy (ACC) of the validation cohort were calculated. External validation also suggests that the model can be used as a tool for initial assessment. Conclusion: Baseline HBsAg in chronic hepatitis B patients were a risk factor for prolonged IFN treatment course with a positive correlation. Ultimately, a personalized model based on baseline HBsAg levels can be established to roughly estimate the duration of interferon therapy prior to treatment initiation, thereby guiding clinical decision-making. [ABSTRACT FROM AUTHOR]

Background Approximately 296 million people have chronic hepatitis B (CHB) caused by hepatitis B virus (HBV). Current standard treatment, nucleos(t)ide analogs, are not efficient enough to eradicate HBV from the hepatocytes. Thus, developing new drugs for CHB is needed to achieve complete cure. Methods Here we established a novel HBV reporter system, HBV-HiBiT-PS2, to screen new drugs for CHB. HBV-HiBiT-PS2 was constructed by adding an HiBiT-tag at the 5′ end of preS2 and introduced this into HepG2-NTCP cells. Culture supernatant containing HBV-HiBiT-PS2 virions was fractionated by sucrose density gradient ultracentrifugation to characterize their components. Replication kinetics and reporter function of HBV-HiBiT-PS2 were determined by analyzing the parameters for HBV replication in the presence or absence of HBV inhibitors. Results HBV-HiBiT-PS2 could be used for monitoring most of the replication cycle of HBV. The effects of well-characterized HBV inhibitors could be evaluated by the HiBiT activity. HBV-HiBiT-PS2 could be specialized for screening secretion inhibitors for hepatitis B surface antigen (HBsAg) because most of the HiBiT activity was derived from subviral particles which are the multimers of HBsAg. Conclusions We demonstrated that HBV-HiBiT-PS2 would be a robust tool for screening novel drugs, especially HBsAg secretion inhibitors, targeted against CHB. [ABSTRACT FROM AUTHOR]

Background 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. Methods 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. Results 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. Conclusions 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. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) surface antigen (HBsAg) seroprevalence was high before the national vaccine policy was introduced in Taiwan, indicating significant HBV infection rates. The success of the HBV immunization program and other preventive measures likely led to decreased HBsAg prevalence among pregnant women. This study reports on the HBV seroprevalence among pregnant women in Taiwan from 2016 to 2021, including those potentially affected by the universal hepatitis B vaccination at birth. Methods: This claim-based cohort study included pregnant women with hospital-based prenatal HBV screening data: 162,662 for HBsAg and 161,729 for HBeAg, from 2016 to 2021. Patient medical records were reviewed to collect information on demographic characteristics and other health conditions. Logistic regression models were used to identify risk factors associated with HBsAg and HBV e antigen (HBeAg) positivity. Results: The seroprevalence for HBsAg and HBeAg during the study period was 4.0% and 0.6%, respectively. HBsAg positivity was highest among women born before July 1984 (pre-vaccination period; 8.6%), decreasing to 2.2% among those born between July 1986 and 1988 (national vaccination implementation) and further declining to 1.1% for those born after 1997. These data underscore the crucial role of large-scale immunization strategies in controlling HBV infections. Similarly, HBeAg positivity was highest among pregnant women born before the vaccination program (~ 1.0%), decreasing significantly to 0.4% for those born after 1989. The results showed geographic variations, potentially reflecting factors such as the mother's age and foreign nationality. However, the birth year was the most crucial factor associated with HBV marker positivity. Conclusions: The implementation of national vaccination programs has demonstrated significant success in reducing HBV seroprevalence among pregnant women, which is particularly evident in the substantial decrease in HBsAg seroprevalence in Taiwan post-July 1986. These findings emphasize the importance of continued and consistent vaccination efforts, supporting the need for ongoing public health strategies to combat HBV infections effectively. [ABSTRACT FROM AUTHOR]

Coexistence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) has been observed in some chronic hepatitis B (CHB) patients (DP patients), but the clinical outcomes and comprehensive characterization of immune micro-environmental changes for this specific population remain inconclusive. In this study, we retrospectively analyze the prognosis of 305 patients in Foshan City, Guangdong Province, China, and also investigated the molecular immunology changes in HBsAg and anti-HBs double positive CHB patients (DP group), CHB patients who had recovered from IFN-ɑ treatment (RP group), and healthy controls (HC group) using T cell receptor (TCR) and B cell receptor (BCR) immune repertoire sequencing. Our findings revealed that 22.30% of DP patients were diagnosed with severe liver disease. Immune repertoire sequencing revealed significant skewing in the diversities of T cell receptor β-chain (TRB) and immunoglobulin heavy chain (IGH) in the DP group compared to the RP group. Unique V(D)J gene combinations, such as IGHV1-18/IGHD3-22/IGHJ5, IGHV1-8/IGHD6-13/IGHJ3, and IGHV1-8/IGHD6-19/IGHJ3, as well as TRBV12-3/TRBD1/TRBJ1-5 and TRBV11-2/TRBD2/TRBJ2-1, exhibited distinct utilization patterns in the DP group. Moreover, the top ten most utilized amino acid motifs in the complementarity determining region 3 (CDR3) of TRB in the DP group showed significant differences from those in the RP group. Notably, motifs such as "xxxYDSSGYx" and "AREx" in the IGH CDR3s were selectively prevalent in the DP group. These findings are expected to provide evidence supporting the poor clinical prognosis of DP patients and offer new insights into the distinct immune micro-environmental changes of this group. [ABSTRACT FROM AUTHOR]

This study evaluated the long-term efficacy and safety of the widely used drugs entecavir (ETV) and tenofovir alafenamide (TAF), as well as the incidence of HCC.A nonrandomized, prospective, observational analysis included 77 patients with chronic hepatitis B who were assigned to continue ETV or switch TAF. After 240 weeks, the mean changes in serum hepatitis B surface antigen (− 0.365 ± 0.069 log IU/mL vs. 0.301 ± 0.039 log IU/mL, p = 0.39) and hepatitis B core-related antigen (− 0.215 ± 0.092 log IU/mL vs. − 0.195 ± 0.056 log IU/mL) were not significantly different between the ETV and TAF groups. There were also no differences between the two groups in estimated glomerular filtration rate (− 5.407 ± 1.660 vs. − 2.666 ± 1.52, p = 0.240), urinary β2-microglobulin β/creatinine (ETV: 2.330 ± 0.374 at baseline and 2.335 ± 0.257 at 240 weeks; TAF: 2.720 ± 0.073 and 2.123 ± 0.310, p = 0.996 and 0.455, respectively) or urinary N-acetyl-β-D-glucosaminidase/creatinine (ETV: 0.040 ± 0.005 at baseline and 0.044 ± 0.004 at 240 weeks; TAF: 0.049 ± 0.005 and 0.053 ± 0.005, p = 0.642 and 0.684, respectively). Finally, no significant difference was found in the incidence of HCC between the ETV and TAF groups (log-rank test, p = 0.08). In conclusion, the long-term observation of this study demonstrated that ETV and TAF have comparable efficacy and safety. Clinical trial registration: UMIN000026465. [ABSTRACT FROM AUTHOR]

Aim: Patients with chronic hepatitis B (CHB) remain at risk for hepatocellular carcinoma (HCC) even with nucleos(t)ide analog therapy. We evaluated risk factors for HCC development, including serum hepatitis B virus (HBV) RNA, hepatitis B core‐related antigen level, and growth differentiation factor 15 (GDF15) level, a predictor of HCC development in patients with chronic hepatitis C. Methods: We collected clinical data and stored serum from CHB patients without a history of HCC who were receiving nucleos(t)ide analog treatment for more than 1 year and whose HBV DNA level was less than 3.0 log IU/mL. We measured the serum levels of HBV RNA and GDF15. Results: Among 242 CHB patients, 57 had detectable HBV RNA, and GDF15 was quantified in all patients. The median GDF15 level was 0.86 ng/mL. Cox proportional hazards analysis revealed that male sex and higher GDF15, FIB‐4 index, alpha‐fetoprotein and gamma‐glutamyl transpeptidase were independent risk factors for HCC. The presence of HBV RNA above the lower limit of quantification was not a risk factor. When we set cutoff values based on the Youden index, the cumulative incidence of HCC was significantly higher in the male, AFP ≥3.0 ng/mL, gamma‐glutamyl transpeptidase ≥22 U/L, FIB‐4 index ≥1.93, and GDF‐15 ≥1.17 ng/mL groups. In patients with no or more than three of these five risk factors, the 10‐year HCC cumulative incidence rates were 0% and 41.0%, respectively. Conclusions: High serum GDF15 is an independent risk factor for the occurrence of HCC in CHB patients treated with nucleos(t)ide analogs. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) can restore exhausted T-cell immunity not only for cancer treatment but also potentially to cure chronic hepatitis B (CHB). Thus, we aimed to determine the previously unclear impact of ICIs on hepatitis B surface antigen (HBsAg) seroclearance in patients with cancer. Consecutive patients with cancer from 2016 to 2020 (cohort 1, n = 118), and hepatocellular carcinoma from 2020 to 2022 (cohort 2, n = 44, as validation) receiving ICIs and positive for HBsAg were retrospectively recruited. An additional HBV-HCC cohort (cohort 3, n = 85) not receiving ICIs served as a control group. Factors associated with HBsAg loss or a HBsAg decline >1 log were analyzed. With median follow-up of 17.5 months, 8 (6.8%) patients in cohort 1 and 4 (9.1%) in cohort 2 achieved HBsAg seroclearance, and an additional four in cohort 1 and one in cohort 2 had a HBsAg decline >1 log. In multivariate analysis, HBsAg <100 IU/ml was associated with HBsAg seroclearance (hazard ratio 6.274, p = 0.028). In the validation cohort, the cumulative incidences of HBsAg loss at months 12 and 24 were 13.0% and 38.4%, respectively, for baseline HBsAg <100 IU/ml, which were significantly higher than those in the control group (p = 0.0267). No case in cohort 3 achieved HBsAg loss within 24 months. Of the 17 cases who achieved HBsAg loss or a decline >1 log, 16 (94.1%) received nucleos(t)ide analogue treatment. The median time to HBsAg loss or HBsAg decline was 16.5 (range 9.6 to 27.5) months. ICIs may accelerate HBsAg seroclearance in patients with cancer and baseline HBsAg <100 IU/ml. This finding provides important information for the design of future trials evaluating the ability of ICIs to induce functional cure in patients with CHB. Immune checkpoint inhibitors (ICIs) can restore exhausted T-cell immunity not only for cancer treatment but also potentially to cure chronic hepatitis B. Functional cure of hepatitis B was observed in patients with cancer or HCC undergoing ICI treatment, and the cumulative incidence of HBsAg loss was higher compared with controls without ICIs. ICIs may accelerate the HBsAg loss in patients with baseline HBsAg levels <100 IU/ml. This finding provides important information for the design of future ICI trials evaluating the ability of ICIs to induce functional cure in patients with CHB. [Display omitted] • ICIs can restore exhausted T-cell immunity, which may potentially cure chronic hepatitis B. • Functional cure of hepatitis B was observed in patients with cancer or HCC undergoing ICI treatment. • ICIs may accelerate HBsAg loss in patients with baseline HBsAg level <100 IU/ml. [ABSTRACT FROM AUTHOR]

Objective: This study aims to determine the prevalence of Occult Hepatitis B and C Infections among Egyptian injection drug users (IDUs) and identify key risk factors contributing to their occurrence within this high-risk group. Methods: In this cross-sectional study, 200 Egyptian IDUs were assessed. Participants were negative for Hepatitis B surface antigen and hepatitis C virus (HCV) RNA, with anti-HCV positive patients who achieved sustained virologic response after treatment included. Quantitative polymerase chain reaction (PCR) was used to detect HCV RNA in plasma and peripheral blood mononuclear cells, while HBV DNA was identified via nested PCR. Comparisons were made between Occult Hepatitis B infection (OBI) positive and OBI negative subgroups, as well as between other comprehensive income (OCI) positive and OCI negative subgroups. A significance level of 0.05 was set, with P-values below this indicating statistical significance. Statistical comparisons between OBI and OCI-positive and negative groups were performed using the Mann–Whitney U test and Chi-square test. Results: OBI was found in 32% of IDUs, while OCI was detected in 42% of IDUs, and was present in 53.6% of seropositive individuals. All OBI patients showed a significant increase in all liver function tests, while OCI patients had significant elevations in alanine transaminase and aspartate transaminase values. HIV coinfection was identified in 39.1% and 26.1% of OBI and OCI cases respectively. OBI and OCI coinfection were detected in 31 patients. Conclusion: Hidden infections such as OBI and OCI remain an overlooked public health issue in Egypt’s IDU population. These findings highlight the need for targeted strategies to address these reservoirs of infection and could inform similar approaches in countries with comparable HBV/HCV epidemiology. [ABSTRACT FROM AUTHOR]

The document "1965: a 'new' antigen in leukemia sera" published in the journal "Hepato-Gastro & Digestive Oncology" relates the discovery of a new antigen in the serum of patients with leukemia in 1965. This discovery was made possible thanks to the technique of starch gel electrophoresis developed by Oliver Smithies in Oxford. The antigen, named "antigen Australia [Au]", was identified in patients with acute leukemias and in individuals predisposed to leukemia, as well as in patients with viral hepatitis. [Extracted from the article]

Background: The management of chronic hepatitis B (CHB) infection is complex due to its natural history, which includes fluctuating viral replication and associated hepatic dysfunction. Aims and Objectives: The study was conducted to evaluate quantitative hepatitis B virus (HBV) DNA and hepatitis B e antigen (HBeAg) titers in patients of chronic HBV infection on entecavir and to find the rate of hepatitis B surface antigen (HBsAg)-positive patients among clinically suspected cases of hepatitis. The objective of the study was to find the rate of HBeAg-positive patients in HBsAgpositive cases on entecavir and to correlate the level of alanine aminotransferase (ALT) with status of HBeAg and HBV DNA level in HBsAg-positive cases on entecavir. Materials and Methods: The study population consisted of 87,600 patients from MG hospital, affiliated with RVRS Medical college in Bhilwara, Rajasthan. Screening of HBsAg was performed using rapid card test method, HBeAg was done by enzyme-linked immunosorbent assay, and HBV DNA was quantified by real-time polymerase chain reaction. Aspartate aminotransferase and ALT were also measured. Results: Blood samples from 87,600 individuals who had a clinical suspicion of having hepatitis B were used in the study. A total of 3650 people (4.1%) had positive HBsAg tests. Of the 3650 (4.1%), 312 (8.54%) experienced a chronic illness. 109 (312) showed positive HBeAg, 102 (312) had elevated ALT enzyme levels, and 117 (312) had positive HBV DNA among the 312 people with CHB. Conclusion: In conclusion, the findings of our study indicate a low prevalence of CHB virus infection. [ABSTRACT FROM AUTHOR]

Prognostic factors for the long‐term evolution of chronic hepatitis B e antigen (HBeAg)‐negative hepatitis B virus (HBV) infection may vary depending on local epidemiology. We aimed to identify these factors in France, where the epidemiology is influenced by diverse immigration. Hepatitis B surface antigen (HBsAg)‐positive, HBeAg‐negative adults with normal transaminase levels and viral loads < 20,000 IU/mL for 1 year, without viral co‐infection or advanced liver disease, were enrolled for a 5‐year follow‐up. A total of 564 patients were recruited from 23 centres (54.4% women, mean age 42.3 ± 12 years, 47.7% from sub‐Saharan Africa). HBV DNA was detectable but < 2000 IU/mL for most (71.3%). Genotypes E (27.8%) and A (20.0%) were predominant. The mean HBsAg titre was 3.8 ± 3.4 log IU/mL, > 1000 IU/mL in 60% of cases, and higher in genotype E (p < 0.0001). During follow‐up, 18 patients received antiviral treatment, 9 for viral reactivation (0.3% per year) and 9 preemptively. HBsAg loss occurred in 39 patients (1.4% per year). These patients were older (p < 0.0001), more frequently treated for dyslipidemia, hypertension or diabetes (p < 0.05), and had lower baseline HBV DNA (p = 0.0112) and HBsAg (p < 0.0001), but similar levels of HBcrAg compared to those who did not clear HBsAg. Baseline HBsAg was the only independent predictor of HBsAg loss (p = 0.009). In this cohort, HBsAg < 153 IU/mL predicted clearance with 87% sensitivity and specificity. In conclusion, baseline HBsAg accurately predicted seroclearance at 5 years in patients with chronic HBeAg‐negative infection, regardless of genotype, sex, or geographical origin, indicating that this marker is widely applicable for reducing the frequency of patient monitoring. [ABSTRACT FROM AUTHOR]

The diagnosis of occult hepatitis B virus (HBV) infection (OBI) is influenced by factors such as the lower limit of detection (LOD) of the HBV DNA test. However, in clinical practice and scientific research, the lower limit of quantification (LOQ) is often misused as the LOD. This study aims to investigate the impact of misuse of the LOD of the HBV DNA test on the detection rate of OBI, as well as the risk factors for OBI. Four hundred twelve patients who were HBsAg‐negative and had undergone high‐sensitivity HBV DNA testing were included in this study. HBV DNA was detected using the Cobas 6800 System with an LOD of 2.4 IU/mL and an LOQ of 10 IU/mL. The effect of using the LOQ as the LOD on the detection rate of OBI was compared, and univariate and multivariate logistic regression analyses were used to explore the risk factors for OBI. (1) Of the 412 patients, 63.3% (n = 261) were male, with a median age of 47 (range 34–55) years. A total of 473 HBV DNA test results were obtained, with 366 individuals undergoing only one HBV DNA test and the remaining 46 patients undergoing 2 to 5 HBV DNA tests (resulting in a total of 107 test results). (2) Considering only the first HBV DNA test result, the detection rate of OBI was 4.1% (17/412). However, when the LOQ (10 IU/mL) was used as the LOD, the detection rate of OBI was only 1.5% (6/412) (p < 0.001). (3) Univariate analysis showed that there were statistically significant differences in age, anti‐HBe positivity rate and anti‐HBc positivity rate between OBI and non‐OBI individuals (p < 0.05). Multivariate regression analysis showed that anti‐HBe positivity was an independent risk factor for OBI in this study (odds ratio [OR] = 3.807, 95% confidence interval [CI]: 1.065–13.617, p = 0.040), while anti‐HBs positivity was a protective factor against OBI (OR = 0.271, 95% CI: 0.093–0.787, p = 0.016). (4) Among the 46 patients who underwent repeated testing, a total of seven individuals were found to be HBV DNA‐positive in the first test, and six individuals tested positive for HBV DNA one or more times in subsequent tests. When OBI was confirmed by ≥ 1 out of 1–5 tests with detectable HBV DNA, the detection rate of OBI in this study could increase from 4.1% to 5.6%. The detection rate of OBI among HBsAg‐negative adult patients attending hepatology departments in this region is 4.1%. Misusing the LOQ as LOD can significantly decrease the detection rate of OBI. The presence of anti‐HBe positivity and undergoing multiple HBV DNA tests can lead to a significant increase in the detection rate of OBI. [ABSTRACT FROM AUTHOR]

Since the discovery of the Australia antigen, now known as the hepatitis B surface antigen (HBsAg), significant research has been conducted to elucidate its physical, chemical, structural, and functional properties. Subviral particles (SVPs) containing HBsAg are highly immunogenic, non-infectious entities that have not only revolutionized vaccine development but also provided critical insights into HBV immune evasion and viral assembly. Recent advances in cryo-electron microscopy (cryo-EM) have uncovered the heterogeneity and dynamic nature of spherical HBV SVPs, emphasizing the essential role of lipid–protein interactions in maintaining particle stability. In this review, recent progress in understanding the molecular architecture of HBV SVPs is consolidated, focusing on their symmetry, lipid organization, and disassembly–reassembly dynamics. High-resolution structural models reveal unique lipid arrangements that stabilize hydrophobic residues, preserve antigenicity, and contribute to SVP functionality. These findings highlight the significance of hydrophobic interactions and lipid–protein dynamics in HBV SVP assembly and stability, offering valuable perspectives for optimizing SVP-based vaccine platforms and therapeutic strategies. [ABSTRACT FROM AUTHOR]

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

Background: Psoriasis patients who are seropositive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) face an elevated risk of hepatitis B virus reactivation (HBVr) when treated with cytokine inhibitors. This study aims to elucidate the risk in this population. Methods: A retrospective chart review was conducted to assess the risk of HBVr in 73 psoriasis patients treated with cytokine inhibitors from 2013 to 2023. Additionally, a systematic review and meta-analysis were performed, pooling data from 10 studies (including our cohort) and adhering to PRISMA guidelines. Statistical heterogeneity was assessed using the I2 statistic, and pooled proportions were calculated using a random effects model. Results: No HBVr cases were observed among the 11 HBsAg+ patients in the cohort. However, two of the sixty-two (3.2%) HBsAg−/HBcAb+ patients experienced reactivation during therapy, with outcomes ranging from spontaneous recovery in one case to death from hepatic failure despite antiviral treatment in the other. The meta-analysis, pooling data from 10 studies, revealed a reactivation rate of 21.2% (95% CI: 9.4–41.0%) in HBsAg+ patients without prophylaxis and 4.4% (95% CI: 2.2–8.7%) in HBsAg−/HBcAb+ patients. Conclusion: Antiviral prophylaxis is essential for HBsAg+ patients receiving cytokine inhibitors, given the high risk of reactivation. Despite the lower risk for HBsAg−/HBcAb+ patients, the potential severity of outcomes demands careful monitoring and timely action. [ABSTRACT FROM AUTHOR]

Objective: Hepatitis B virus (HBV), a significant global health concern, remains a source of infection despite the availability of effective vaccines. The progression of the disease is influenced by HBV antigens and autoimmune reactions. A deficiency in the immunomodulatory vitamin D is associated with the severity of various illnesses. The purpose of this research was to explore the relationship between HBV serological test results and 25-hydroxyvitamin D levels. Materials and Methods: The study included 120,004 HBV serological tests (Hepatitis B surface antigen (HBsAg), Hepatitis B e-antigen (HBeAg), anti-HBsAg, anti-HBeAg, antibodies to Hepatitis B core immunoglobulin G (anti-HBc IgG), and anti-HBc IgM) and 62.835 25-hydroxyvitamin D tests. Results: In spring, summer, and fall, 25-hydroxyvitamin D levels in HBsAg-positive individuals were lower compared to HBsAg-negative individuals. Conversely, 25-hydroxyvitamin D levels in individuals positive for anti-HBsAg were higher than those in anti-HBsAg-negative individuals across all seasons. Furthermore, in both cases of 25-hydroxyvitamin D deficiency and optimal 25-hydroxyvitamin D levels, individuals positive for anti-HBsAg showed higher 25-hydroxyvitamin D values than those negative for anti-HBsAg. Additionally, individuals positive for anti-HBc IgG demonstrated higher 25-hydroxyvitamin D levels compared to anti-HBc IgG-negative individuals during winter and fall. Moreover, 25-hydroxyvitamin D levels in individuals negative for anti-HbeAg were found to be below the optimal range. Conclusion: In conclusion, there may be a relationship between 25-hydroxyvitamin D levels and hepatitis B serological test positivity. Therefore, vitamin D levels should be monitored in populations affected by HBV. [ABSTRACT FROM AUTHOR]

Functional cure of chronic hepatitis B (CHB)—defined as sustained seroclearance of hepatitis B surface antigen (HBsAg) with unquantifiable hepatitis B virus (HBV) DNA at 24 weeks off treatment, is an optimal treatment endpoint. Nonetheless, it cannot be consistently attained by current treatment modalities. RNA interference (RNAi) is a novel treatment strategy using small-interfering RNA (siRNA) or antisense oligonucleotide (ASO) to target HBV post-transcriptional RNA, in turn suppressing viral protein production and replication. Hence, RNAi has indirect effects in promoting host immune reconstitution against HBV. Multiple RNAi therapeutics have entered phase II/III clinical trials, demonstrating potent, dose-dependent, and sustainable effects in suppressing HBsAg. Incidences of HBsAg seroclearance, particularly with the use of ASO, have also been documented. The combination of RNAi with other antivirals/immunomodulators (e.g. pegylated interferon), have shown promising results in potentiating RNAi effects and enhancing treatment durability. Further research will be required to establish predictors of response, optimal treatment protocols, and long-term outcomes in patients on RNAi. RNAi therapeutics have shown promising results and will likely be the keystone of future HBV treatment. [ABSTRACT FROM AUTHOR]

Due to the lack of agents that directly target covalently closed circular DNA and integrated HBV DNA in hepatocytes, achieving a complete cure for chronic hepatitis B (CHB) remains challenging. The latest guidelines recommend (hepatitis B surface antigen) HBsAg loss as the ideal treatment target for improving liver function, histopathology, and long-term prognosis. However, even after HBsAg loss, hepatitis B virus can persist, with a risk of recurrence, reactivation, cirrhosis, and hepatocellular carcinoma. Therefore, follow-up and surveillance are still necessary. With increasing treatment options available for achieving HBsAg loss in patients with CHB, developing effective surveillance strategies has become crucial. Recent studies on outcomes following HBsAg loss provide new insights for refining current surveillance strategies, though further improvement is needed through long-term observation and follow-up. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) infection remains a major health challenge in Nigeria, with high prevalence rates among pregnant women. The prevalence of overt and occult hepatitis B infection (HBIOV and HBIOC) among pregnant women was investigated to understand the burden and associated risk factors in this population. Methods: A cross-sectional study was conducted among 200 pregnant women. Socio-demographic and clinical data were collected, and blood samples were screened for hepatitis B surface antigen (HBsAg) and hepatitis B virus DNA (HBV-DNA) using Enzyme-Linked Immunosorbent Assay (ELISA) and real time Polymerase Chain Reaction max Eco 48 system. Data were analyzed using GraphPad Prism software (v6) and Statistical Package for the Social Sciences (IBM SPSS 23.0). A significance level of P ≤ 0.05 was considered statistically significant. Results: The overall prevalence of hepatitis B infection was 6.0% (12/200), comprising 2.5% HBIOC and 3.5% HBIOV. The participants, aged 19 to 43 years, were predominantly married (89.5%) and urban-dwelling (69.0%), with diverse educational levels and occupations. There were no statistically significant differences in demographic factors such as age, marital status, or education between HBIOC and HBIOV groups. However, significant associations were observed between HBV infection and risk factors including blood transfusion (p = 0.01), cigarette exposure (p = 0.03), and alcohol consumption (p = 0.01). Viral load was significantly higher in the HBIov group [4.84 log IU/mL (IQR: 4.00–9.14)] compared to the HBIoc group [2.30 log IU/mL (IQR: 2.19–3.00)] (p = 0.001). Conclusion: The findings reveal a 6.0% prevalence of hepatitis B infection among pregnant women, with 3.5% overt and 2.5% occult infections. The results emphasize the need for HBV DNA testing in screening protocols to detect occult and overt HB infections and address key risk factors to improve antenatal care and prevention strategies. [ABSTRACT FROM AUTHOR]

Background: A multivariate predictive model was constructed using baseline and 12-week clinical data to evaluate the rate of clearance of hepatitis B surface antigen (HBsAg) at the 48-week mark in patients diagnosed with chronic hepatitis B who are receiving treatment with pegylated interferon α (PEG-INFα). Methods: The study cohort comprised CHB patients who received pegylated interferon treatment at Mengchao Hepatobiliary Hospital, Fujian Medical University, between January 2019 and April 2024. Predictor variables were identified (LASSO), followed by multivariate analysis and logistic regression analysis. Subsequently, predictive models were developed via logistic regression, random forest (RF), gradient boosting decision tree (GBDT), extreme gradient boosting (XGBoost), and support vector machine (SVM) algorithms. The efficacy of these models was assessed through various performance metrics, including the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and F1 score. Results: This study included a total of 224 individuals diagnosed with chronic hepatitis B. The variables baseline log2(HBsAg), gender, age, neutrophil count at week 12, HBsAg decline rate at week 12, and HBcAb at week 12 were closely associated with functional cure and were included in the predictive model. In the validation term, the logistic regression model had an AUC of 0.858, which was better than that of the other machine learning models (AUC = 0.858,F1 = 0.753). Consequently, this model was selected for the development of the predictive tool. Conclusions: The combined use of the baseline log2(HBsAg) value, HBsAg decline rate at week 12, gender, neutrophil count at week 12, and age can serve as a foundational predicting model for anticipating the clearance of HBsAg in individuals with chronic hepatitis B who are receiving PEG-INFα therapy. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B infection is a major public health concern in Vanuatu, with approximately 9% of the general population estimated to be living with chronic hepatitis B. Most new infections are due to mother-to-child transmission (MTCT). Hepatitis B vaccination is available in Vanuatu, but coverage rates for first dose within 24 h of birth and third dose are suboptimal. While treatment of chronic hepatitis B infection with tenofovir disoproxil fumarate (TDF) is available in country, there is no capacity to test hepatitis B e antigen and limited capacity to test hepatitis B virus (HBV) DNA viral load, which is a current eligibility requirement for women in pregnancy to access hepatitis B prophylaxis for MTCT per National guidelines. Recently, the World Health Organization guidelines have been updated to recommend universal peripartum antiviral prophylaxis (PAP) of pregnant women living with hepatitis B to prevent MTCT of HBV, without assessment of viral load in places without access to testing. However, these recommendations are conditional based on low-certainty evidence. The aim of this trial is to evaluate the effectiveness and safety of universal PAP and provide evidence for the global guidelines. Methods: A single arm field trial compared to real world control sites will be conducted in Vanuatu involving pregnant women attending antenatal care services with positive HBsAg rapid tests. Participants at the control sites will undergo routine care. Participants at the intervention sites will all receive oral TDF prophylaxis from second trimester to completion of infant primary hepatitis B vaccination schedule. Primary data analysis will be by intention-to-treat. Initial analyses will be unadjusted comparisons of the intervention sites and control sites. Adjusted analyses will be performed, as needed, and presented in addition to unadjusted comparisons. Discussion: This study will provide evidence of acceptability, effectiveness and cost-effectiveness of prophylaxis for all women with hepatitis B during pregnancy, as per the updated WHO guidelines, compared with current practice. The outcome of this trial will provide critical information to inform national and global guidelines around universal peripartum antiviral prophylaxis for hepatitis B during pregnancy. Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN: ACTRN12623001202651p. Registered 21 November 2023. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated steatotic liver disease (MASLD) is common in patients with obesity and diabetes and can lead to serious complications. This study aimed to evaluate fundus photographs using artificial intelligence to explore the relationships between diabetic retinopathy (DR), MASLD, and related factors. In this cross-sectional study, we included 1,736 patients with a history of diabetes treatment or glycated hemoglobin (HbA1c) levels of ≥6.5%. All participants were negative for hepatitis B surface antigen and hepatitis C virus antibody and were selected from 33,022 examinees at a health facility in Japan. Fundus photographs were analyzed using RetCAD software, and DR scores were quantified. The presence of DR was determined using two cutoffs: sensitivity (CO20) and specificity (CO50). Steatotic liver (SL) stages were assessed via ultrasound and fibrosis indices and classified into three groups: no SL (SL0), SL with low fibrosis (SL1), and SL with high fibrosis (SL2). Odds ratios (ORs) for the risk of DR associated with each SL stage were calculated using logistic regression, adjusted for age, sex, body mass index, HbA1c, C-reactive protein level, and alcohol consumption. The risk of DR was lower in the SL1 (OR: 0.63, 0.54) and SL2 (OR: 0.64, 0.77) groups compared to the SL0 group at CO20 for both the Fibrosis-4 Index (FIB-4) and the non-alcoholic fatty liver disease fibrosis score (NFS), respectively. Additionally, higher levels of cholinesterase were consistently associated with a reduced risk of DR (FIB-4: OR 0.52, NFS: OR 0.54) at CO50. This study demonstrates that MASLD was associated with a reduced risk of DR, with cholinesterase levels providing further protective effects, highlighting the need for further research into the protective mechanisms and refinement of DR evaluation techniques. The standardized AI evaluation method for DR offers a reliable approach for analyzing retinal changes. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions Hepatitis C virus (HCV) infection is a risk factor of intrahepatic cholangiocarcinoma (ICC). However, the impact of HCV infection control status on prognosis after surgery for ICCs is still unclear.This multicenter retrospective study included patients who underwent curative resection for ICCs. The sera of 56 patients tested positive for anti‐HCV antibody and negative for hepatitis B surface antigen (HCV group). Additionally, the sera of 358 patients tested negative for anti‐HCV antibody and hepatitis B surface antigen (NBNC group). In the HCV group, 33 of 56 patients achieved sustained virologic response (SVR) for HCV (SVR group), whereas 23 patients did not (non‐SVR group). To investigate the prognostic impact of HCV infection control status in the whole study cohort and in patients with solitary ICC without lymph node metastasis (StN0 study cohort), the postoperative prognosis of the SVR, non‐SVR, and NBNC groups was compared.In the whole study cohort, there were no significant differences in terms of recurrence‐free survival (RFS) or overall survival among the three groups. Based on the multivariate Cox regression analysis, non‐SVR was an independent unfavorable prognostic factor of RFS. In the StN0 study cohort, the non‐SVR group had a significantly lower RFS than the NBNC and SVR groups. Based on the multivariate analysis, non‐SVR was an independent unfavorable prognostic factor of RFS.The achievement of SVR for HCV infection in patients with HCV infection‐related ICCs is associated with a better RFS after surgery for HCV‐related ICCs, particularly solitary ICC without lymph node metastasis. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions Microvascular invasion (MVI) affects the prognosis and treatment of hepatocellular carcinoma (HCC); however, its preoperative diagnosis is challenging. Analysis of computed tomography (CT) images using radiomics can detect MVI, but its effectiveness depends on the imaging conditions. We compared the efficacies of radiomics, clinical, and combined models for predicting MVI in HCC using nonstandardized scanning protocols.This multicenter study included 533 patients who underwent hepatic resection for HCC. Patients were divided randomly into training (n = 426) and test groups (n = 107). We manually extracted 3D CT features in hepatic arterial, portal venous, and venous phases. The radiomics model was trained by machine learning. A logistic regression model was developed based on clinical information, and a fused model was created integrating clinical information and radiomics prediction score (Rad_Score). We calculated areas under the receiver operating characteristic curves (AUCs) for the radiomics, clinical, and mixed models in the test groups.The clinical model incorporated hepatitis B virus surface antigen, tumor diameter, and log‐transformed α‐fetoprotein and des‐gamma‐carboxyprothrombin. The AUCs of the radiomics and clinical models were comparable (p = 0.76). Rad_Score was not an independent significant factor in the fused model (p = 0.40) and its addition did not improve the accuracy of the clinical model alone (p = 0.51).A clinical model is as effective as a CT radiomics model for predicting MVI status in patients with HCC based on real‐world scanning data, and integration of both models does not improve the predictive performance compared with a clinical model alone. [ABSTRACT FROM AUTHOR]

The article discusses the efficacy and safety of xalnesiran in combination with immunomodulators for treating chronic hepatitis B virus (HBV) infection. Topics include the role of xalnesiran as an RNA interference therapeutic and its impact on HBsAg loss in patients with chronic HBV; the use of immunomodulators, specifically pegylated interferon alfa-2a and ruzotolimod, in combination with xalnesiran; and the global burden of chronic HBV infection.

BACKGROUND: Xalnesiran, a small interfering RNA molecule that targets a conserved region of the hepatitis B virus (HBV) genome and silences multiple HBV transcripts, may have efficacy, with or without an immunomodulator, in patients with chronic HBV infection. METHODS: We conducted a phase 2, multicenter, randomized, controlled, adaptive, open-label platform trial that included the evaluation of 48 weeks of treatment with xalnesiran at a dose of 100 mg (group 1), xalnesiran at a dose of 200 mg (group 2), xalnesiran at a dose of 200 mg plus 150 mg of ruzotolimod (group 3), xalnesiran at a dose of 200 mg plus 180 Bg of pegylated interferon alfa-2a (group 4), or a nucleoside or nucleotide analogue (NA) alone (group 5) in participants with chronic HBV infection who had virologic suppression with NA therapy. The primary efficacy end point was hepatitis B surface antigen (HBsAg) loss (HBsAg level, <0.05 IU per milliliter) at 24 weeks after the end of treatment. Safety was also assessed. RESULTS: Among 159 participants (30,30,34,30, and 35 in groups 1 through 5, respectively), the primary end-point event occurred in 7% (95% confidence interval ICI], 1 to 22) of those in group 1, in 3% (95% CI, 0 to 17) of those in group 2, in 12% (95% CI, 3 to 28) of those in group 3, in 23% (95% CI, 10 to 42) of those in group 4, and in none (95% CI, 0 to 10) of those in group 5. In groups 1 through 5, respectively, HBsAg seroconversion occurred in 3%, none, 3%, 20°/0, and none of the participants at 24 weeks after the end of treatment. HBsAg loss with or without seroconversion occurred only in participants with a screening HBsAg level below 1000 IU per milliliter. In groups 1 through 5, respectively, grade 3 or 4 adverse events occurred in 17°/0, 10°/0, 18°6, 50%, and 6% of the participants, with the most frequent event being an elevated alanine aminotransferase level. CONCLUSIONS: Among participants with chronic HBV infection who had virologic suppression with NA therapy, treatment with xalnesiran plus an immunomodulator resulted in HBsAg loss at 24 weeks after the end of treatment in a substantial percentage of participants. Grade 3 or 4 adverse events were not uncommon. (Funded by F. Hoffmann-La Roche; Piranga ClinicalTrials.gov number, NCT04225715. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aims Methods Results Conclusions Trial Registration Despite European guidelines recommending anti‐hepatitis D virus (HDV) screening for all hepatitis B surface antigen (HBsAg)‐positive cases, screening rates remain insufficient.We analysed anti‐HDV screening rates in primary care and implemented prospective HDV screening in HBsAg‐positive cases identified in the preventive medical examination from the age of 35 (“Check‐Up 35+”).From 2012 to 2021, we reviewed anti‐HDV and HDV RNA test rates in HBsAg‐positive patients at 11 sites of a large German laboratory group. From 2022 to 2023, we prospectively screened HBsAg‐positive samples from the “Check‐Up 35+” for anti‐HDV. Anti‐HDV positive patients were then contacted again for HDV RNA testing.Retrospectively, 2792/13,905 (20%) HBsAg‐positive cases were tested for anti‐HDV, with 142/2792 (5.1%) being positive. HDV RNA was tested in 57/142 (40%) anti‐HDV‐positive cases, with 26/57 (46%) being positive. In the prospective screening, 1159/225,901 (0.51%) individuals were HBsAg‐positive. Of these, 700 (60%) were tested for anti‐HDV, with 18/700 (2.6%) positive test results. 4/18 (22%) were successfully contacted again for HDV RNA analysis, with one case testing positive. Neither the HBsAg nor the anti‐HDV positive result was known prior to screening in these cases. Anti‐HDV testing could not be performed in 459/1159 (40%) HBsAg‐positive cases, primarily due to insufficient blood sample volume (310/459 cases, 68%), with others missed due to logistical errors.Retrospective data show insufficient anti‐HDV screening in clinical routine. The prospective anti‐HDV screening provides a blueprint for using existing hepatitis B virus screening programms for population‐based HDV double reflex testing, provided that adequate logistical prerequisites are established.German Clinical Trial Register: DRKS00029180 [ABSTRACT FROM AUTHOR]