Search Results (10)

Over the past decade, the incidence of infectious syphilis has been on the rise in the general Chinese population. Consequently, Treponema Pallidum (TP) testing has been proposed as a surrogate marker for sexually transmitted pathogens and for monitoring risky sexual behaviors among blood donors globally. In addition, sexual contact with individuals chronically infected with hepatitis B virus (HBV) is recognized as one of the primary routes of HBV transmission. Blood donors may acquire HBV infection through sexual contact with chronically infected partners, particularly with occult hepatitis B infections (OBIs), which are characterized by intermittent and extremely low viral loads. Therefore, the prevalence of OBIs among syphilis-positive blood donations and the corresponding risks to blood safety require further investigation. This study aimed to investigate the prevalence of OBIs among syphilis-positive blood donors and assess the surrogate value of TP testing for evaluating OBI-related risks to blood supply. After routine screening using serological assays and nucleic acid testing (NAT), blood donation samples with positive anti-TP enzyme-linked immunosorbent assay (ELISA) results were collected and further confirmed by the Treponema Pallidum Particle Agglutination Assay (TPPA). For blood donations confirmed positive for syphilis, further tests were performed to characterize whether the donations had HBV co-infection, including electrochemiluminescence immunoassay (ECLI) for the detection of hepatitis B surface antigen (HBsAg), anti-hepatitis B surface antibody (anti-HBs), hepatitis B e antigen (HBeAg), anti-hepatitis B e antibody (anti-HBe), and anti-hepatitis B core antibody (anti-HBc). Additionally, quantitative real-time polymerase chain reaction (qPCR) was used for HBV DNA quantification, and nested PCRs for the S and basal core promoter/precore (BCP/PC) region were conducted in combination with high-volume nucleic acid extraction. Subsequently, molecular characterization of HBV DNA in these co-infected samples was carried out by DNA sequencing to analyze the viral genetic features. Of 252 anti-TP ELISA+ donations screened from 64,871 blood samples, 138 (138/250, 55.2%) donations were confirmed syphilis-positive but NAT−, among which 78 (78/138, 56.5%) were anti-HBc-positive, and 88 (88/138, 63.7%) had anti-HBs. Notably, seven donations (7/138, 5.1%) were diagnosed as OBI co-infections, and available sequence analysis revealed that three cases were genotype B and one case was genotype C. In addition, several mutations in the S region of the HBV genome were identified, including Q101R, K122R, Q129H, T131N, M133T, G145R, and Y161F mutations. Furthermore, nucleotide mutations such as T1719G, A1752T, G1896A, and A1762T/G1764A in the BCP/PC regions were also detected in these OBI donations. These mutations may contribute to the extremely low HBV viral loads and/or failure in HBsAg detection, collectively leading to OBIs. These data indicate that syphilis screening of blood donors has potential to serve as an additional safeguard measure for excluding donations co-infected with OBIs. The high prevalence of undetected OBIs in syphilis-positive blood donors further supports that syphilis screening has the potential to serve as a surrogate marker for HBV-related risks in the blood supply. Full article

Objectives: This study aimed to evaluate very low HBV DNA viral load below the limit of quantification and to identify correlational factors in different patient groups, including individuals with chronic hepatitis B (CHB), occult HBV infection (OBI), and others. Methods: We retrospectively analyzed 390 patients with very low-level viremia (VLLV). HBV DNA levels were measured in plasma samples using real-time quantitative PCR (qPCR). Serological markers were evaluated in serum samples using chemiluminescence microparticle immunoassay (CMIA). Demographic variables, HBV serological markers (anti-HBs, anti-HBe, anti-HBc), and DNA results were evaluated. Results: The study included 193 CHB patients with maintained virological suppression and 197 patients in the other group; of which, 60 patients had occult hepatitis B infection (HBV DNA positive, HBsAg negative) and 137 had no occult hepatitis B infection. Very low viral load was more common in men (53.3%) and in individuals aged ≥50 years (63.3%). In univariate analysis, OBI was associated with anti-HBe (odds ratio (OR) = 2.874, 95% CI: 1.255–6.579, p = 0.013), and anti-HBc seropositivity (OR = 5.750; 95% CI: 2.626–12.591, p < 0.001). In multivariate analysis, anti-HBe positivity and anti-HBc positivity were independently associated with OBI. Anti-HBs positivity was independently and inversely associated with OBI. Conclusions: In patients with VLLV cohort, anti-HBc and anti-HBe seropositivity were independently associated with detectable but unquantifiable HBV DNA. Although anti-HBe positivity reflects reduced viral replication, it does not indicate complete viral suppression and may be detected at very low viremia levels, especially in occult HBV infection. These findings highlight the complex interplay between viral replication dynamics and host immune responses across the VLLV spectrum, characterize the serological landscape associated with detectable but unquantifiable HBV DNA, and warrant validation in prospective studies. Full article

In October 2020, the International Coalition to Eliminate Hepatitis B Virus (ICE-HBV) updated the biomarker framework; they underscored major advances in the understanding of viral and immunologic markers, yet highlighted persistent gaps in their clinical integration. This is particularly the case in low- and middle-income regions, where HBV remains a substantial public health problem, including in the pediatric population. To synthesize contemporary evidence, a structured literature search was performed across PubMed/MEDLINE, Scopus, and Web of Science. Classical biomarkers—including HBeAg, HBV DNA, and quantitative HBsAg—remain central for disease staging and therapeutic monitoring, while emerging markers enhance precision in risk stratification: HBcrAg, which correlates strongly with intrahepatic cccDNA activity and virological rebound after NA discontinuation; serum HBV RNA, which offers additional insight into transcriptional activity, which is particularly relevant for RNA-targeted therapies; and quantitative anti-HBc (qAnti-HBc), which reflects stronger humoral imprinting and more competent HBV-specific immune memory, and is consistently associated with fewer ALT flares and reduced virological rebound at end of treatment. Despite these advances, assay standardization, genotype-related variability, and limited pediatric data constrain broad clinical application. Integrating classical and emerging biomarkers into personalized therapeutic algorithms offers substantial potential for refining treatment decisions, predicting post-treatment outcomes, and advancing HBV elimination strategies in diverse clinical settings. Full article

Vietnam faces a hyperendemic burden of hepatitis B virus (HBV) infection, but the prevalence of occult HBV infection (OBI) and its underlying molecular mechanisms in healthy populations remain poorly understood. This study aimed to characterize the serological and molecular HBV profile of a healthy Vietnamese adult cohort in Southern Vietnam. We assessed the prevalence of occult HBV infection (OBI) and HBsAg-positivity (serving as a proxy for probable chronic infection). In this cross-sectional study, 397 healthy adults from Southern Vietnam underwent serological screening for HBsAg, anti-HBs, and anti-HBc. All participants were screened for HBV DNA using a high-sensitivity PCR assay (LOD ≥ 5 IU/mL). For all viremic cases, the full Pre-S/S region was sequenced to determine genotype and characterize escape mutations. We uncovered a high prevalence of both HBsAg-positivity (17.6%) and OBI (9.3% HBsAg-negative, HBV DNA-positive). Serological analysis revealed a massive, age-dependent reservoir of past exposure (63.7% anti-HBc) characterized by a high and increasing prevalence of the anti-HBc only profile (31.5%), a key serological marker for OBI. This trend contrasted sharply with a steep age-related decline in protective anti-HBs. The viral landscape was dominated by genotypes B (73.8%) and C (26.2%), with sub-genotypes B4 and C1 being the most prevalent. Critically, individuals with OBI carried a significantly higher burden of S gene escape mutations compared to those with HBsAg-positivity (p < 0.001). Canonical escape variants, including sG145R (21.6%), sK141R/T/E/Q (24.3%), and sT116N/A/I/S (18.9%), were exclusively or highly enriched in the OBI group. A LASSO-logistic model based on this mutational profile successfully predicted occult infection with high accuracy (AUC = 0.83). A substantial hidden reservoir of occult HBV infection exists within the healthy adult population of Vietnam, driven by a high burden of S gene escape mutations. These findings highlight the significant limitations of conventional HBsAg-only screening. They also underscore the need for comprehensive molecular surveillance to address the true scope of HBV viremia, hopefully enabling a reduction in hidden transmission of clinically significant viral variants. Full article

Background: Hepatitis B is an infectious disease of worldwide importance and of great interest to transfusion medicine. The Amazon region has areas of high endemicity, outlining a worrying scenario for transfusion and epidemiological safety. Objective: To analyze the profiles of serological and molecular markers for HBV of blood donors from HEMOAM. Methods: Blood donors with different patterns of reactivity in serological and molecular screening for HBV were tested for viral load by the qPCR method at the reference center for liver diseases in the state of Amazonas. Results: A total of 230,591 donors were tested, with 3104 (1.34%) found reactive for HBV and 2790 (89.9%) found reactive for isolated anti-HBc. Viral load was not detected in 100% of donors reactive only to HBsAg, while 100% of donors with positive anti-HBc and positive HBsAg or HBV NAT demonstrated a detectable viral load. We also detected one case of occult hepatitis B (0.03%) only with reactive HBV NAT and five donors (0.2%) with positive anti-HBc and HBV NAT. Conclusions: With this result, the great importance of the anti-HBc test for the unsuitability of blood donors was verified, as well as the fundamental introduction of the HBV NAT test in screening for hepatitis B in Brazilian blood banks, as this was the only way to detect the viral infection burden in asymptomatic donors who previously would not be treated, which contributed to the maintenance of the endemicity of hepatitis B in the Brazilian Amazon. Full article

During chronic hepatitis B virus (HBV) infection, the seroclearance of hepatitis B e antigen (HBeAg) is an important event and a significant surrogate endpoint of all current therapeutic strategies. The prediction of HBeAg seroclearance can help assess the benefits of therapy in patients during or before therapy initiation. The quantitation of HBV core antibodies (qAnti-HBc) is a new non-invasive biomarker for solving multiple diagnostic dilemmas. A systematic review and meta-analysis of studies that measured qAnti-HBc in patients who achieved HBeAg seroclearance were performed through PubMed, Web of Science (WoS) and SCOPUS electronic database searches. Nineteen articles were included in the systematic review, comprising 3434 chronically infected patients (1014 with and 2420 without HBeAg seroclearance). Sixteen publications with data regarding qAnti-HBc levels were included in the meta-analysis. The baseline level of qAnti-HBc antibodies was significantly higher in patients with than without HBeAg seroclearance (SMD = 0.88, 95%CI SMD = 0.56–1.2, p < 0.001). The same conclusion was reached for patients originating from Asia (SMD = 0.94, 95%CI SMD = 0.55–1.33) and for the qAnti-HBc antibodies among adult HBV patients with therapy-induced HBeAg seroclearance (SMD = 0.90, 95%CI SMD = 0.54–1.25, p < 0.001). The systematic review and meta-analysis provide evidence of the role of qAnti-HBc as a promising biomarker for predicting HBeAg seroclearance in chronically infected patients. Full article

Background: Patients with lymphoma and chronic hepatitis B virus infection need to be treated with both chemotherapy and nucleotide analogue (NA) therapy. However, dynamic changes in HBV DNA loads with increasing chemotherapy cycles are lacking. It is unknown whether HBV replication markers, namely, the quantitative hepatitis B core antibody (qAnti-HBc), HBV RNA, and the hepatitis B virus core-related antigen (HBcrAg), are also markers for predicting HBV reactivation (HBVr). Methods: From 29 June 2010 to 6 December 2021, the data of patients with single-site diffuse large B-cell lymphoma and HBV infection (HBsAg+ and HBsAg−/anti-HBc+) were collected from a hospital medical record system, retrospectively. Serum HBV DNA loads (using real-time fluorescent quantitative PCR tests), qAnti-HBc levels (using a newly developed chemiluminescent particle immunoassay), HBV RNA levels (using the simultaneous amplification testing method based on real-time fluorescence detection), and HBcrAg levels (using a Lumipulse G HBcrAg assay) were tested, and factors related to HBVr were analyzed. Results: Under NAs, the HBV DNA loads of 69 HBsAg+ lymphoma patients declined from 3.15 (2.13–4.73) lg IU/mL to 1.00 (1.00–1.75) lg IU/mL, and further declined to 1.00 (1.00–1.04) lg IU/mL at the end of a 24-month follow-up. The qAnti-HBc levels decreased gradually during chemotherapy in HBsAg+ lymphoma patients (F = 7.090, p = 0.009). The HBV RNA and HBcrAg levels remained stable. A multivariate analysis revealed that higher qAnti-HBc levels (1.97 ± 1.20 vs. 1.12 ± 0.84 lg IU/mL, OR = 6.369, [95% CI: 1.523–26.641], p = 0.011) and higher HBV RNA levels (1.00 ± 1.13 vs. 0.37 ± 0.80 lg copies/mL, OR = 3.299, [95% CI: 1.229–8.854], p = 0.018) were related to HBVr in HBsAg−/anti-HBc+ lymphoma patients. Conclusions: HBV DNA loads declined under NAs during chemotherapy in lymphoma patients. In HBsAg−/anti-HBc+ lymphoma patients, a higher level of baseline serum qAnti-HBc and HBV RNA levels can predict the likelihood of HBVr during chemotherapy. Full article

The hepatitis B virus core protein (HBcAg) is a highly immunogenic particulate antigen. Nearly all patients with persistent or resolved hepatitis B virus (HBV) infection show seropositivity for hepatitis B core antibody (anti-HBc), which appears in the early stage of infection and is mostly present for life. Traditionally, the anti-HBc is regarded as an evidential serological marker of HBV infections. In the last ten years, several studies revealed the predictive value of quantitative anti-HBc (qAnti-HBc) level in the treatment response and clinical outcome of chronic HBV infections, implying new insights into this classic marker. Overall, qAnti-HBc should be regarded as an indicator of the host’s immune response specific to HBV, which correlates with HBV-related hepatitis activity and liver pathology. This review summarized the latest understanding of the clinical values of qAnti-HBc for differentiating the CHB phase, predicting treatment response, and providing disease prognosis. Moreover, we also discussed the possible mechanism of qAnti-HBc regulation during different courses of HBV infection. Full article

The present-day management of hepatitis B virus (HBV) infection relies on constant and appropriate monitoring of viral activity, disease progression and treatment response. Traditional HBV infection biomarkers have many limitations in predicting clinical outcomes or therapy success. Quantitation of HBV core antibodies (qAnti-HBc) is a new non-invasive biomarker that can be used in solving multiple diagnostic problems. It was shown to correlate well with infection phases, level of hepatic inflammation and fibrosis, exacerbations during chronic infection and presence of occult infection. Further, the level of qAnti-HBc was recognised as predictive of spontaneous or therapy-induced HBeAg and HBsAg seroclearance, relapse after therapy discontinuation, re-infection after liver transplantation and viral reactivation upon immunosuppression. However, qAnti-HBc cannot be relied upon as a single diagnostic test to solve all dilemmas, and its diagnostic and prognostic power can be much improved when combined with other diagnostic biomarkers (HBV DNA, HBeAg, qHBsAg and anti-HBs antibodies). The availability of commercial qAnti-HBc diagnostic kits still needs to be improved. The comparison of results from different studies and definitions of universal cut-off values continue to be hindered because many methods are only semi-quantitative. The clinical utility of qAnti-HBc and the methods used for its measurement are the focus of this review. Full article

Even though an approved vaccine for hepatitis B virus (HBV) is available and widely used, over 257 million individuals worldwide are living with chronic hepatitis B (CHB) who require monitoring of treatment response, viral activity, and disease progression to reduce their risk of HBV-related liver disease. There is currently a lack of predictive markers to guide clinical management and to allow treatment cessation with reduced risk of viral reactivation. Novel HBV biomarkers are in development in an effort to improve the management of people living with CHB, to predict disease outcomes of CHB, and further understand the natural history of HBV. This review focuses on novel HBV biomarkers and their use in the clinical setting, including the description of and methodology for quantification of serum HBV RNA, hepatitis B core-related antigen (HBcrAg), quantitative hepatitis B surface antigen (qHBsAg), including ultrasensitive HBsAg detection, quantitative anti-hepatitis B core antigen (qAHBc), and detection of HBV nucleic acid-related antigen (HBV-NRAg). The utility of these biomarkers in treatment-naïve and treated CHB patients in several clinical situations is further discussed. Novel HBV biomarkers have been observed to provide critical clinical information and show promise for improving patient management and our understanding of the natural history of HBV. Full article