Search Results (142)

Background and Clinical Significance: Left atrial myxoma is the most common benign primary cardiac tumor and is associated with embolic and hemodynamic complications. Complete surgical excision is the treatment of choice, while postoperative cardiovascular rehabilitation is essential for functional recovery. Case Presentation: We report the case of a 75-year-old woman with arterial hypertension, dyslipidemia, and chronic venous insufficiency (Clinical–Etiological–Anatomical–Pathophysiological (CEAP) class 2), and chronic hepatitis B virus (HBV) infection who underwent surgical excision of a left atrial myxoma and was subsequently admitted three weeks postoperatively for phase II cardiovascular rehabilitation. The postoperative course was complicated by transient atrial fibrillation, peripheral edema, pleural effusion, and progressive purpuric lesions of the lower limbs. Laboratory and immunological evaluation revealed positive cryoglobulins, markedly elevated rheumatoid factor (1058 UI/mL) and IgM levels (715 mg/dL), reduced complement levels (C3, C4), normocytic normochromic anemia, microscopic hematuria, and elevated ALT (156 U/L), AST (142 U/L), total bilirubin (1.4 mg/dL), and INR (1.6), suggestive of hepatic inflammatory activity. HBV status was scheduled for evaluation through Gastroenterology referral (HBV DNA viral load, serological markers: HBsAg, HBeAg, anti-HBe), as our Cardiology Rehabilitation Clinic lacks the possibility of evaluation. After systematic exclusion of alternative etiologies, secondary cryoglobulinemic vasculitis in the context of chronic HBV infection with biochemical evidence of hepatic activity was considered the most plausible diagnosis. Conclusions: This case highlights the complexity of managing elderly patients after cardiac tumor surgery, particularly in the presence of systemic comorbidities. Early recognition of extracardiac complications and an individualized, multidisciplinary strategy are essential to optimize outcomes. Full article

Background: Hepatitis B virus infection has been linked to liver cancer and may influence metastasis in other malignancies, but its role in gastric cancer liver metastasis (GCLM) is unclear. Methods: We retrospectively analyzed 776 gastric cancer patients with HBV testing. HBV infection was defined as HBsAg+ (chronic HBV, CHB) or HBsAg− with HBcAb/HBeAb+ (occult HBV, OHB). Among the 776 patients, 300 (38.6%) were classified as HBV+. The association between HBV infection and GCLM was evaluated, and propensity score matching (PSM) was performed to adjust for age and gender. Furthermore, the impact of HBV infection on overall survival (OS) was analyzed. Results: GCLM occurred in 19.5% of patients. HBV+ patients had a higher GCLM prevalence than HBV− patients (25.3% vs. 15.8%; p = 0.001), persisting after PSM (25.3% vs. 15.3%; p = 0.002). HBV infection was an independent risk factor for GCLM (OR = 2.563, p < 0.001). Both OHB and CHB groups showed significantly higher GCLM rates than HBV− patients in univariate and multivariate analyses. However, OS did not differ between groups (p = 0.737). Conclusion: HBV infection significantly increases the risk of liver metastasis in gastric cancer. Enhanced surveillance for liver metastasis is warranted in these patients. Full article

Background/Objectives: HBeAg-positive chronic hepatitis B (CHB) patients with very high viral replication are often clinically considered a homogeneous, low-risk population. However, substantial biochemical, virological, and fibrosis-related heterogeneity may exist. This study aimed to characterize this heterogeneity in treatment-naive, HBeAg-positive CHB patients with ultra-high viral loads (HBV DNA ≥ 7.0 log₁₀ IU/mL). Furthermore, we sought to identify predictors of significant fibrosis and detect clinically relevant discordant phenotypes, such as silent disease progression despite normal alanine aminotransferase (ALT) levels. Methods: This single-center, retrospective, cross-sectional study analyzed consecutively screened eligible patients. A liver stiffness measurement (LSM, kPa) and controlled attenuation parameter (CAP, dB/m) were obtained via transient elastography. Significant fibrosis was defined as an LSM ≥ 7.0 kPa. Statistical evaluations included Spearman’s correlation, multivariable regression, ALT-LSM stratification, and K-means clustering. Results: Among 413 included patients, age and aspartate aminotransferase (AST) emerged as independent risk factors for significant fibrosis, whereas log10 HBV DNA and log10 HBsAg were independent negative predictors. Patients with HBsAg ≥ 25,000 IU/mL exhibited significantly lower LSM values than those with lower HBsAg levels. Notably, 18.4% of patients with strictly normal ALT (≤40 U/L) presented with an LSM ≥ 7.0 kPa, indicating silent progression. Cluster analysis further identified two distinct patient phenotypes characterized by differing age, ALT, viral load, and fibrosis profiles. Conclusions: An ultra-high viral load in HBeAg-positive CHB does not guarantee a uniformly benign clinical state. By quantifying biochemical, virological, and fibrotic heterogeneity, this study highlights a critical subgroup with silent fibrosis progression that risks being overlooked by ALT-based assessments alone. 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

Background/Objectives: Chronic hepatitis B (CHB) and type 2 diabetes mellitus (T2DM) frequently coexist. This study aimed to investigate the impact of T2DM and glycemic control on antiviral efficacy in CHB patients. Methods: This single-center, retrospective cohort study included treatment-naïve CHB patients who initiated nucleos(t)ide analogue (NA) therapy between January 2019 and January 2024. The primary endpoint was a complete virological response (CVR), defined as achieving HBV DNA levels below 20 IU/mL after 48 weeks of treatment. Results: The CHB + T2DM group (n = 81) demonstrated a significantly lower CVR rate than the CHB group (n = 106) (26.0% vs. 41.2%, p = 0.038). Multivariate analysis identified T2DM as an independent negative predictor of a CVR (OR = 0.400, 95% CI: 0.196–0.815, p = 0.012). Within the CHB + T2DM subgroup, adequate glycemic control (HbA1c < 7%) was associated with a higher CVR (38.7% vs. 16.7%, p = 0.034). Patients newly diagnosed with diabetes at enrollment showed a higher rate of HBeAg loss than those with pre-existing diabetes (57.1% vs. 10.0%, p = 0.036). Regarding antiviral regimens, entecavir-treated CHB + T2DM patients had a lower CVR than CHB controls (18.8% vs. 46.2%, p = 0.015). Furthermore, tenofovir-based regimens showed a more favorable antiviral trend than entecavir in CHB patients with T2DM. Conclusions: Comorbid T2DM was an independent risk factor for impaired antiviral efficacy in CHB patients. Optimal glycemic control may improve virological outcomes. These findings suggest that the early diagnosis and management of T2DM could enhance antiviral treatment efficacy in CHB patients. Full article

Background/Objectives: Chronic hepatitis B (HBV) and C (HCV) remain major public health challenges in Romania despite vaccination and antiviral therapy. Understanding infection patterns in different healthcare settings is essential for targeted elimination strategies. Methods: We conducted the prospective screening phase of the RE-LINK project (January–June 2025) through two nationwide private laboratory networks. Adults undergoing routine testing were screened for HBsAg and anti-HCV. HBsAg-positive samples were further analyzed for HBV DNA, HBeAg, anti-HBe, anti-HDV, and HDV RNA, while anti-HCV-positive cases were tested for HCV RNA. Risk factors were assessed using chi-square and logistic regression analyses. Results: Among 9149 individuals (66.6% women with a median age of 53 years), HBsAg prevalence was 2.9%, and anti-HCV was 1.3%, both increasing significantly with age (p < 0.001). Of all HBsAg-positive individuals, 12.5% had undetectable HBV DNA, 70.4% had low viremia (<2000 IU/mL), and 17.1% had high viral loads. Anti-HDV antibodies were detected in 2.3% of HBsAg-positive subjects, all with detectable HDV RNA (range 1250–680,000 IU/mL). Significant risk factors for HBsAg positivity were male sex, older age, urban residence, physician-indicated testing, neuropsychiatric comorbidity, family or parental hepatitis, and institutional/orphanage care, while HBV vaccination and moderate alcohol use were protective. Anti-HCV positivity correlated with older age, cardiovascular disease, elevated transaminases, transfusions, surgery, and HIV co-infection. Only 20.2% of anti-HCV-positive individuals were viremic. Conclusions: Private-laboratory screening reveals residual low-replicative HBV and declining viremic HCV, while community programs uncover HDV and advanced disease in vulnerable groups. A coordinated approach integrating private, community, and hospital-based pathways can accelerate elimination efforts and ensure that HDV is not overlooked. Full article

Occult hepatitis B infection (OBI) and mutated forms of the hepatitis B virus (HBV) represent diagnostic challenges, especially in individuals with atypical serological profiles. This study explores the molecular characteristics of HBV in HBsAg-negative women of childbearing age exhibiting atypical serological markers. We selected 100 HBsAg-negative sera from a cohort of 433 women aged 15–45 years. Additional HBV serological markers (anti-HBc, anti-HBs, HBeAg, anti-HBe) were assessed. Real-time PCR targeting the HBV S gene was performed on samples presenting atypical profiles. Socio-demographic and clinical correlates were also analyzed. Atypical serological profiles were identified in 23% of HBsAg-negative women, including combinations such as isolated anti-HBe positivity and anti-HBe with anti-HBc. Among these, none tested positive for HBV DNA by real-time PCR. Atypical profiles were more prevalent among women attending antenatal consultations and those aged under 25 years. The absence of detectable HBV DNA suggests either very low viral loads, resolved past infections, or serological artifacts due to mutated HBV strains. The high frequency of atypical serological patterns among HBsAg-negative women underscores the need to refine molecular diagnostic tools for detecting occult or mutated HBV. Further sequencing and genotypic characterization studies are warranted. Full article

Background and Aim: The management of patients with chronic Hepatitis B Virus (HBV) HBeAg-negative infection in the indeterminate-grey zone (GZ) remains debatable. We conducted a systematic review and meta-analysis to compare these patients with those with chronic HBV HBeAg-negative infection (inactive carriers; IC/HBeAg-negative), regarding the severity of liver inflammation and fibrosis and the risk of developing hepatocellular carcinoma (HCC). Methods: A literature search was conducted to identify all published studies comparing GZ/HBeAg-negative patients with IC/HBeAg-negative patients. Data on the severity of liver inflammation and fibrosis were extracted, and pooled relative risks (RR) and 95% confidence intervals (CI) were calculated. The risk of HCC was estimated by pooled hazard ratios (HR). A random-effects meta-analysis model was performed using R v4.1.2. Results: Eleven studies were finally included. GZ/HBeAg-negative patients had significantly higher mean HBV-DNA and alanine transferase (ALT) levels, compared to their IC/HBeAg-negative counterparts (4089.9 ± 4840.5 vs. 215.9 ± 318.1 IU/mL; p = 0.0004, and 39.6 ± 26.9 IU/L and 20.1 ± 7.6 IU/L/; p < 0.0001, respectively). GZ/HBeAg-negative patients showed a trend towards a higher risk of significant liver inflammation (RR: 5.11; 95%CI: 0.68–38.33; p = 0.1), F2/F3 fibrosis (RR: 2.13; 95%CI: 0.89–5.1; p = 0.09), and cirrhosis (RR: 14.39; 95%CI: 0.5–417.08; p = 0.12), respectively, compared to IC/HBeAg-negative patients. After a median follow-up of 6.2 years, the former group demonstrated a significantly higher risk of developing HCC (HR: 4.7; 95% CI: 1.4–15.6; p < 0.0001). Conclusions: GZ/HBeAg-negative patients have a higher risk of developing HCC compared to IC/HBeAg-negative patients, which raises concerns about the potential need to initiate treatment in this patient group. Full article

Background/Objectives: The accurate evaluation of the fibrosis stage is critical for improving chronic hepatitis B (CHB) management and patient outcomes. This study aimed to compare the diagnostic accuracy of non-invasive fibrosis markers with liver biopsy for detecting significant, advanced fibrosis and cirrhosis. We further investigated the diagnostic performance of non-invasive markers according to HBeAg status to provide further insight into their clinical utility across patient subgroups. Methods: This single-center retrospective study included 536 treatment-naive patients with CHB who underwent liver biopsy. Patients were categorized into four groups according to the fibrosis stage: “no significant fibrosis” (F0–F2), “significant fibrosis” (F3–F6), “advanced fibrosis” (F4–F6), and “cirrhosis” (F5–F6). AAR, AAPRI, APRI, API, FIB-4, GPR, and S–index were compared among these groups. Results: In total, 536 treatment-naïve patients were analyzed (63.2% male; mean age 44.8 ± 12.9 years), of whom 25.4% were HBeAg-positive. API, FIB 4, GPR, and S-Index showed good performance (area under the curve [AUC] ≥ 0.8–0.9) in defining advanced fibrosis (≥F4), AAPRI, AAR, API, and APRI showed good performance ([AUC] < 0.700) in defining cirrhosis. The analysis showed that GPR had the highest AUC for ≥F3 (0.719) and ≥F4 (0.838), while FIB 4 had the highest AUC for cirrhosis (0.865). Conclusions: These findings highlight the value of non-invasive markers as inexpensive and easily applicable methods for clinicians in assessing the stage of liver fibrosis. The integration of these scores into the routine monitoring of chronic hepatitis B patients is expected to expand, enhancing clinical decision-making and reducing the necessity for liver biopsies. Full article

Chronic hepatitis B virus (HBV) infection is a major health problem that leads to approximately one million deaths every year worldwide. Mother-to-child transmission (MTCT) is the major cause of chronic HBV infection. HBV e antigen (HBeAg) is a secretory viral protein and modulates the immunological landscape of the newborn to promote HBV persistence. HBeAg actively reprograms innate and adaptive immunity. Mechanistically, HBeAg regulates macrophage polarization, suppresses dendritic cell and natural killer (NK) cell activities, impairs T cell and B cell functions, and promotes the expansion of myeloid-derived suppressor cells (MDSCs). These multifaceted effects contribute to immune tolerance and persistent HBV infection in the offspring of carrier mothers. Clinically, HBeAg status is a critical determinant for MTCT risk stratification and intervention, particularly in resource-limited settings. Despite advances in neonatal immunoprophylaxis and maternal antiviral therapy, residual transmission of HBV persists. Emerging approaches targeting HBeAg directly or restoring antiviral immunity offer promising avenues for breaking immune tolerance and achieving HBV elimination. This review summarizes current understanding of HBeAg-mediated immune modulation and highlights strategies that are being used to disrupt MTCT and treat HBV patients. Full article

Background: Hepatocellular carcinoma (HCC) frequently develops in patients with chronic hepatitis B and C. Early detection is critical, but current methods, including ultrasound and AFP, have suboptimal accuracy. Objectives: This study aimed to evaluate the predictive performance of protein induced by vitamin K absence or antagonist-II (PIVKA-II) and alpha-fetoprotein (AFP) testing, alone and in combination, for HCC development. Methods: A retrospective cohort study at a single university center included 242 CHB and 181 CHC patients. Data on demographics, clinical status, laboratory parameters, and imaging were collected, with fibrosis and steatosis assessed by FibroScan^®. Serum AFP and PIVKA-II were measured, but measurements of PIVKA-II in patients receiving vitamin K antagonists were excluded from the analysis. HCC diagnosis and staging followed clinical guidelines. Cox regression and ROC analyses identified independent predictors and evaluated biomarker accuracy for HCC detection. Results: HCC incidence was comparable between cohorts (5.0% in CHB vs. 5.5% in CHC). Both AFP and PIVKA-II independently predicted HCC development in multivariate models adjusted for age and sex. The combined biomarker score (AFP × PIVKA-II) showed superior predictive accuracy with hazard ratios of 1.38 (CHB) and 1.36 (CHC). ROC analyses demonstrated high discriminative ability for PIVKA-II (AUC ~0.81) and AFP (AUC ~0.83) in both cohorts. Additional independent predictors were chronic alcohol abuse, cirrhosis, and higher liver stiffness measurements. Specific viral factors such as HBeAg positivity and HCV subgenotype 1b were also associated with increased HCC risk. Conclusions: AFP and PIVKA-II are independent, valuable biomarkers for HCC risk in chronic hepatitis B and C. Combined use improves early detection, aiding timely treatment. These results support adding PIVKA-II to AFP in surveillance, but larger studies are needed to confirm the findings and refine cut-off values. Full article

Hepatitis B virus (HBV) particles containing HBV RNA are secreted into the blood; these RNA-containing particles are non-infectious byproducts of the replication cycle and are distinct from mature, DNA-containing virions. The proportion of these particles increases during nucleoside/nucleotide analog therapy, but the clinical significance of serum HBV RNA remains unclear. We evaluated longitudinal changes in serum HBV RNA and their association with the antiviral efficacy of nucleoside/nucleotide analog therapy. Eighty-six patients with chronic HBV infection (baseline HBV DNA ≥ 5.0 Log IU/mL and ALT < 500 U/L) treated with entecavir (ETV, N = 80) or tenofovir alafenamide (TAF, N = 6) were included. Serum HBV RNA was quantified using Cobas HBV RNA (RUO) at baseline, week 12, and week 48. Associations with clinical variables and treatment response were analyzed. Baseline HBV RNA correlated with HBsAg, HBV DNA, and hepatitis B core-related antigen. Both HBV DNA and RNA tended to decrease with advanced liver fibrosis. HBV DNA and RNA declines did not differ between HBeAg-positive and -negative patients, but the HBV RNA/DNA ratio at week 48 was significantly higher in HBeAg-positive cases (p < 0.001). Patients with baseline ALT ≥ 100 U/L showed significantly lower RNA levels at weeks 12 and 48 (p = 0.004, p < 0.001). While HBV DNA decline was similar between ETV and TAF (p = 0.076), RNA decline was significantly greater with TAF at week 12 (p = 0.027). Serum HBV RNA reflects intrahepatic viral replication and may not be influenced by fibrosis progression. HBV RNA decline during nucleoside/nucleotide analog therapy differed between ETV and TAF, suggesting drug-specific effects on viral RNA dynamics. Full article

Background: Chronic hepatitis B (CHB) remains being a major public health threat, and currently existing CHB therapies have limited efficacy and side effects. We have recently developed a vaccine termed VVX001 based on a recombinant fusion protein consisting of the preS domain of the large surface protein of hepatitis B virus (HBV) fused to grass pollen allergen peptides. VVX001 has been shown to induce preS-specific antibodies in grass pollen allergic patients, and sera of immunized subjects inhibited HBV infection in vitro. Methods: In this study we investigated if immunization with VVX001 can induce preS-specific antibodies in CHB using the adeno-associated virus (AAV)-HBV murine model of CHB. Six groups of C57BL/6 female mice (n = 6) were transduced with AAV-HBV or AAV-Empty, and after six weeks, they were immunized five times with 20 µg of aluminum hydroxide-adsorbed VVX001 or preS or vehicle (Alum alone). Serum samples were taken continuously. Two weeks after the last immunization, spleen and liver mononuclear cells were collected. Serum reactivity to preS and preS-derived peptides was assessed by ELISA. B-cell responses were measured by ELISPOT assay, and intrahepatic lymphocyte (ILH) counts were determined by FACS. HBV DNA, HBsAg, HBeAg, ALT, and AST were assessed using commercial kits. Results: Our results show that VVX001 induces preS-specific IgG antibodies that cross-react with different HBV genotypes A-H and are directed against the sodium taurocholate co-transporting polypeptide (NTCP) receptor binding site of preS both in mice with and without HBV. Actively immunized AAV-HBV-treated mice had a higher number of intrahepatic lymphocytes than vehicle-vaccinated and mock-transduced animals. Conclusions: These findings encourage performing further trials to study the potential of VVX001 for therapeutic vaccination against CHB. Full article

In the modern era of HIV treatment, people co-infected with HIV and HBV still face poor liver outcomes, including liver fibrosis, liver cirrhosis, and hepatocellular carcinoma. We investigated baseline characteristics and long-term liver function outcomes in 435 people living with HIV and HBV co-infection, focusing on HCC-associated point mutations (PMs) and PreS region deletion mutations. PMs were present in 72.9% of participants and were associated with male predominance, lower HBV genotype C prevalence, reduced HBV DNA and HBeAg levels, and higher HBsAg and HBeAb positivity. However, PMs did not significantly impact liver function or fibrosis progression over six years of ART follow-up. In contrast, PreS deletions were found in 21.8% of cases and stratified into PreS1, PreS2, and PreS1+2 deletions. PreS2 and PreS1+2 deletions were linked to older age, higher HBsAg and AFP levels, elevated liver enzymes, and lower platelet counts. These groups also exhibited significantly worse liver fibrosis markers (APRI and FIB-4), with PreS2 deletions consistently showing the highest values throughout the follow-up. Despite the initial improvement with ART, patients with PreS2 and PreS1+2 deletions maintained higher fibrosis and cirrhosis risks over six years. In summary, while PMs were not predictive of liver disease progression, PreS deletion mutations (especially in the PreS2 region) were associated with poorer liver outcomes, indicating their potential as biomarkers for fibrosis risk in co-infected individuals with long-term ART. Full article

In a previous study, eight chronically HBV-infected nucleos (t)ide analog (NA)-naïve patients began receiving entecavir (ETV) concomitant with a single ARC-520 HBV siRNA injection. This single dose of ARC-520 (SD) was followed by 6–8 months of ETV alone before the patients received 4–9 monthly doses of ARC-520, the multi-dose (MD) period, while continuing ETV. Quantities of HBV DNA, RNA, and antigens were measured from serum and a liver biopsy collected ~30 months after the last MD from five patients. All full-length HBV transcripts from the livers were characterized. Viral parameters and HBV transcripts from patients were compared to these measurements collected at multiple points in ARC-520 + ETV-treated chronically HBV-infected chimpanzees. Multiple forms of HBx mRNA were observed, and these differed between chimpanzees and patients. Products of cccDNA were greatly decreased in patients who were previously highly viremic and HBeAg+, although a biopsied patient had similar amounts of cccDNA to the highly viremic HBeAg+ chimpanzees. The comparison of all HBV transcripts and cccDNA levels between patients and chimpanzees demonstrate the transcriptional silencing of cccDNA following the siRNA treatment of patients but not the chimpanzees that received a different treatment regimen. Results from this small study suggest that continued NA treatment during and between periods of HBV antigen re-expression post-siRNA treatment enhanced viral parameter reductions. Full article