Search Results (134)

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

Background/Objectives: This study evaluates the effects of a personalized exercise program on symptoms (pain, fatigue, sleep, cognitive function, physical function), resilience, and health-related quality of life (HRQOL) and compares the effectiveness of in-person versus telehealth delivery. Methods: A secondary data analysis was conducted on two 12-week randomized control pilot studies for solid tumor cancer survivors. One study involved in-person home visits with telephone follow-ups. The second utilized weekly exercise recommendations via a smartphone app. Both studies had control participants who received the standard care. Symptoms, resilience, and HRQOL were measured at baseline and after 12 weeks. Paired t-tests were conducted for intervention effects and ANCOVA for group differences, adjusting for age and education. Results: The analysis included 75 program completers: 15 in-person (iHBE), 38 telehealth (TEHE), and 22 who received standard care. Those receiving exercise interventions reported improvements in physical (t = 3.0, p < 0.01) and mental fatigability (t = 3.1, p < 0.01) at program completion compared to baseline. Comparing the mean changes between participants receiving exercise interventions in-person and via telehealth, there were no significant differences between the two delivery methods except perceived visuo-perceptual cognitive difficulty (F = 3.55, p = 0.027), where telehealth showed a slight advantage. Conclusions: The study provides initial evidence of the effectiveness of a telehealth personalized exercise on fatigability and cognitive difficulty, suggesting it is a potential viable alternative to in-person intervention. Further research with a larger cohort is essential to ascertain the effects of these interventional modalities on cancer-related health outcomes. Full article

Hepatitis B is a serious infectious disease that threatens the health of all mankind. In this study, we isolated and extracted hydroxytyrosol from Lindernia ruellioides with anti-hepatitis B virus (HBV) activity. The structure of hydroxytyrosol was identified by the nuclear magnetic resonance technique. HepG2.2.15 cell models were used to detect the anti-HBV activity and liver protection of hydroxytyrosol in vitro. Hydroxytyrosol can inhibit hepatitis B surface antigen (HBsAg) and hepatitis B e-antigen (HBeAg). The IC₅₀ values of HBsAg and HBeAg were 4.02 mg/L and 5.19 mg/L, respectively. At the highest concentration of hydroxytyrosol, the inhibition rates of supernatant and intracellular HBV DNA were 75.99% and 66.33%, respectively. Hydroxytyrosol was less toxic to normal human hepatocytes. Molecular docking showed that hydroxytyrosol was bound to three amino acid residues of HBV polymerase with a binding energy of −7.0 kcal/mol. This study provided data for the development and utilization of Lindernia ruellioides and the research and development of anti-hepatitis B virus drugs. Full article

Hepatitis B virus (HBV) genetic variability, shaped by high mutation rates and selective pressures, complicates its management and increases the emergence of drug-resistant and immune-escape variants. This study aims to analyze immune escape mutations (IEMs) and drug resistance mutations (DRMs) in patients with HBV infection exposed to antiviral therapies and exhibiting detectable plasma HBV viremia. This monocentric retrospective real-life study was carried out at the ASST Spedali Civili di Brescia, Italy, from 2015 to 2023. A total of 102 consecutive patients with detectable serum HBV-DNA exposed to at least one NA and for whom a drug resistance assay was available were included in our study. HBV sequences were amplified, sequenced, and analyzed for mutations using Geno2pheno and Stanford University tools. Phylogenetic analysis and statistical regression were performed to confirm genotypes and identify mutation patterns and associated risk factors. Our study shows a 38.2% prevalence of DRMs, with M204I/V (95%) and L180M (64%) being the most common, and a 43% prevalence of IEMs, primarily in the major hydrophilic region. Genotype D3 exhibited a higher mutation burden than other genotypes. Significant associations were found between HBsAb presence and increased IEM burden, while HBeAg was protective against DRMs. Atypical serological profiles were observed in 18.6% of patients, including cases of HBV reactivation under immunosuppressive therapy. This study highlights the high prevalence of IEMs and DRMs in a real-world setting, particularly among HBV genotype D3 carriers. These findings underscore the importance of mutation surveillance to guide therapeutic strategies, vaccine design, and public health policies to address the challenges posed by HBV genetic variability. Full article

This study aimed to assess the prevalence of HDV (hepatitis delta virus), HCV (hepatitis C virus), and HIV (human immunodeficiency virus) coinfections among HBsAg-positive patients and to determine the severity of liver fibrosis and biochemical markers. Furthermore, the study sought to evaluate the noninvasive fibrosis scores (APRI and FIB4) in predicting the severity of liver disease in patients with hepatitis B. A retrospective analysis of 1434 patients with chronic HBV admitted between January 2020 and December 2024 was conducted at Sincan Tertiary Hospital. The positivity rates of the following antibodies were the focus of the study: anti-HDV, anti-HCV, and anti-HIV. In addition to these, the levels of HIV-RNA, HCV-RNA and HBV-DNA, as well as several biochemical markers (ALT, AST, INR, albumin, bilirubin and platelet count) were also evaluated. The APRI and FIB-4 scores were calculated. Of the 1434 patients, 49 (3.4%) tested positive for anti-HDV, 784 were screened for anti-HCV, and 749 were screened for anti-HIV. The positivity rates were 3.4% (27/784) and 3.4% (26/749), respectively. According to ROC analysis, the FIB-4 score had a statistically significant effect on predicting anti-HDV negativity (AUC = 0.59, p = 0.031). However, the APRI score was not a significant predictor for anti-HDV positivity (AUC = 0.53, p > 0.05). APRI and FIB-4 scores did not have a statistically significant discriminatory power in predicting anti-HCV and anti-HIV positivity (p > 0.05). The cut-off value for the FIB-4 score in predicting anti-HDV positivity was 1.72, with a sensitivity of 61.4% and a specificity of 42.9% (p = 0.031). Among the HCV/RNA-positive patients (n = 5), all were male, and two also had positive anti-HBe results with undetectable HBV/DNA levels. One HIV/RNA-positive patient, a foreign national, was confirmed to have HIV/HBV/HDV infection. All HBsAg-positive patients should undergo routine anti-HDV testing. Vaccination programmes are vital in preventing the spread of HDV. Dual screening strategies are essential for identifying infected individuals and developing prevention and treatment programmes. Anti-HDV positivity indicates advanced liver fibrosis, emphasising the importance of screening and monitoring. However, the limited accuracy of the APRI and FIB-4 scores for detecting coinfections highlights the need to integrate noninvasive methods with molecular diagnostics for precise management. Full article

Hepatitis B virus (HBV) is a causative reagent that frequently causes progressive liver diseases, leading to the development of acute hepatitis, chronic hepatitis, cirrhosis, and eventually hepatocellular carcinoma. Despite several antiviral drugs, including interferon-α and nucleotide derivatives, being approved for clinical treatment of HBV, critical issues remain unresolved, e.g., their low-to-moderate efficacy and adverse side effects, as well as resistant strains. In this study, twenty-three matrine derivatives were synthesized, and their antiviral effects against HBV were evaluated. Of these, eleven compounds inhibited HBeAg secretion significantly more than the positive control, lamivudine (3TC). Among the compounds synthesized in this study, compounds 4a and 4d had the most potent inhibitory activity, with IC₅₀ value of 41.78 and 33.68 μM, respectively. Compounds 1h, 4a, and 4d were also subjected to molecular docking studies. These compounds inhibited viral gene expression and viral propagation in a cell culture model. Thus, we believe our compounds could serve as resource for antiviral drug development. Full article

Globally, an estimated 254 million people are living with chronic hepatitis B virus (HBV) infection, yet only 10.5% have been diagnosed, underscoring the urgent need to expand testing to meet the World Health Organization’s HBV elimination targets by 2030. Many HBV diagnostic tests remain expensive and inaccessible in resource-limited settings. In this study, we demonstrate how individually sourced, commercially available reagents can be used to develop cost-effective in-house assays for total DNA isolation, HBV viral load quantification by (q)PCR, and qHBsAg and qHBeAg measurement using sandwich ELISA. These assays were validated using known HBV-positive and HBV-negative plasma samples (genotypes A–F) and HepAD38 cells treated with tenofovir disoproxil fumarate (TDF). DNA isolation using a commercial column-based kit was compared to a high-throughput, column-free method, allowing for HBV quantification from 50 µL of plasma with lower limits of detection (LLOD) of 1.8 × 10³ and 1.8 × 10⁴ HBV DNA copies IU/mL, respectively. Both commercial and in-house DNA isolation methods yielded comparable half-maximal effective concentration (EC₅₀) values in TDF-treated HepAD38 cells. Additionally, in-house sandwich ELISA assays were developed for quantitative HBsAg and HBeAg detection, with LLOD values of 0.78 IU/mL and 0.38 PEI U/mL (Paul Ehrlich Institute), respectively. The in-house reagents for DNA isolation, molecular testing, and serological detection of HBV were estimated to be at least 10 times more cost-effective than commercially available kits, highlighting their potential for broader application in resource-limited regions. Full article

In recent decades, considerable advances have been achieved in the treatment of chronic hepatitis B. However, the currently available drugs have shortcomings. In this context, several natural compounds have been proposed as potential agents to improve either the outcome of antiviral treatment or the progression of chronic infection, with curcumin being one of the most evaluated compounds due to its pleiotropic antiviral activity. The aim of this study was to characterize the effect and mechanism of curcumin on hepatitis B virus (HBV) replication in two different experimental models. Treatment of HepG22.15 and HBV-transfected Huh7 cells with curcumin revealed that the phytochemical differentially modulated HBV replication in both cell lines. In HepG22.15 cells, the addition of curcumin had no effect on viral DNA, pregenomic RNA (pgRNA), and e antigen (HBeAg) levels, while it decreased Precore RNA and s antigen (HBsAg) levels. Conversely, in Huh-7 cells, curcumin significantly increased viral progeny more than tenfold, as well as HBV RNAs and viral antigens. Furthermore, the analysis of the cellular mechanisms associated with the modulation of viral replication revealed that in Huh-7 cells, curcumin-induced cell cycle arrest in the G2/M phase and the modulation of genes involved in proliferation, cell cycle progression, and apoptosis, whereas no changes in cell cycle progression and gene expression were observed in HepG22.15 cells. In conclusion, curcumin elicits a differential cellular response in two hepatoma cell lines, which, in the case of Huh-7 cells, would provide an optimal cellular setting that enhances HBV replication. Therefore, the antiviral effect of this phytochemical remains controversial. Full article

Hepatitis B virus (HBV) infections remain a significant global health challenge, especially in low- and middle-income countries where access to healthcare services is often limited. This study aimed to assess the prevalence of hepatitis B virus (HBV), hepatitis delta virus (HDV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) co-infections in a cohort of 426,528 patients tested for HBsAg in Romania between 2018 and 2023. Of the 17,082 HBsAg-positive individuals (4.0% prevalence), the highest HBV positivity rates were observed in the 30–39 and over 60 age groups. Chronic HBV infection was identified in 13.2% of the cohort, with 3.6% testing positive for HBeAg, indicating active viral replication. Co-infection rates were 11.3% for HDV, 1.4% for HCV, and 0.45% for HIV. The incidence of HDV co-infection increased significantly from 2018 to 2023, particularly in older populations. HCV co-infection was more prevalent in individuals aged 50–59 and over 60, with a declining trend from 2020 onward. The study also revealed a weak correlation between liver enzyme levels (ALT and AST) and HBV viral load, suggesting that liver function tests may not fully reflect the severity of HBV infection. HIV co-infection was notably rare compared to other regions, likely due to regional healthcare interventions. The findings from our study highlight the need for targeted interventions, particularly for high-risk groups such as older adults and middle-aged individuals, to reduce the burden of chronic HBV and its complications. Full article