Search Results (3,623)

Background: Hepatocellular carcinoma (HCC) is a prevalent malignancy with high mortality, often arising in the context of chronic liver diseases. Heme oxygenase-1 (HO-1), an inducible enzyme involved in heme degradation, has been implicated in both hepatoprotection and tumor progression. This study evaluates the expression of HO-1 in HCC and its association with clinicopathological features and patient survival. Materials and Methods: We retrospectively analyzed 58 HCC cases diagnosed between 2018 and 2023 at “Sf. Spiridon” Emergency County Hospital, Iasi. HO-1 expression was assessed immunohistochemically and quantified using a semi-quantitative immunoreactivity score (IRS). Statistical correlations between HO-1 expression and clinical, pathological, and survival parameters were evaluated using univariate analysis, ROC curves, and Kaplan–Meier survival models. Results: High HO-1 expression (IRS > 1) was significantly associated with hepatitis C virus etiology (p = 0.004, V = 0.381), vascular invasion (p = 0.019, V = 0.309) and perioperative anticoagulant therapy (p = 0.007, V = 0.352). However, HO-1 expression did not correlate with overall survival (OS). In contrast, solid growth pattern (p = 0.030) and serum α-fetoprotein levels of 10–99 ng/mL (p = 0.022) were negatively associated with OS. Conclusions: HO-1 expression in HCC was found to be associated with vascular invasion, but not with overall survival. While this may indicate a potential link to certain aggressive tumor features, the overall role of HO-1 in HCC biology remains unclear. These findings suggest that HO-1 should be considered an exploratory rather than definitive prognostic marker, and further research is warranted to clarify its function and potential utility, including investigation of its detectability in biological fluids for non-invasive monitoring. Full article

Background: Pregnancy is a time when women are uniquely engaged with the healthcare system and are often motivated to participate in activities directed toward improvement of their own health and ensuring the health of their unborn child, which also provides an opportunity for healthcare interventions such as treatment for hepatitis C virus (HCV) infection. Methods: This was a multi-site, prospective, open-label, pharmacokinetic (PK) study conducted at two large maternity hospitals in Melbourne, Australia, to evaluate the safety and pharmacokinetics of antenatal sofosbuvir (SOF) and velpatasvir (VEL) treatment administered for 12 weeks during the second and third trimester. Five women were recruited and underwent detailed PK assessments across three visits. Results: Compared to historical data in non-pregnant women, SOF area under the concentration curve (AUC) and maximum concentrations (Cmax) were 60% and 49% higher in pregnancy, respectively. In contrast, exposure to the inactive metabolite of SOF, GS-331007, was 43% lower in pregnancy. Both Cmax and AUC for VEL in pregnancy were similar to values reported in historic non-pregnant women (~21% lower in pregnant women). SOF/VEL was safe and well tolerated. Conclusions: These results add to the limited published experience prescribing antivirals in pregnancy and provide further support for a larger ongoing prospective study and other efforts to support HCV treatment in pregnancy. Full article

Background: Since the introduction of the hepatitis B virus (HBV) vaccination program in Oman in 1990, the HBV prevalence has markedly decreased. However, hepatitis D virus (HDV) infection, which is associated with progressive liver disease in patients with chronic HBV, remains understudied in the Omani population. This study aimed to estimate HDV’s seroprevalence, characterize its virological and clinical features, and identify factors associated with anti-HDV positivity among adult Omani patients with chronic HBV infection. Methods: We conducted a multicenter cross-sectional study in 2024 at two referral hospitals and two polyclinics in Oman. Adult Omani patients with chronic HBV (HBsAg-positive for >6 months) were enrolled. Demographic, clinical, laboratory, imaging, and elastography data were collected. The total anti-HDV antibodies were tested using an ELISA; HDV RNA was tested for anti-HDV-positive or equivocal results. Liver Fibrosis was assessed non-invasively through liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE); FibroScan^® and clinical evaluation. Ridge (penalized) logistic regression identified predictors independently associated with anti-HDV positivity. Results: Among 639 patients (59.3% male; mean age of 46.6 ± 8.8 years), 36 patients were anti-HDV-positive, resulting in an HDV seroprevalence of 5.6% (95% CI: Exact 3.98–7.71; Wilson 4.10–7.70). Only one anti-HDV-positive patient had detectable HDV RNA, which became undetectable on follow-up without HDV treatment. The anti-HDV-positive patients were more frequently female and had a higher frequency of prior blood transfusions. In a penalized multivariable analysis, blood transfusions were independently associated with anti-HDV positivity (OR of 19.94), whereas male sex was associated with lower odds of being anti-HDV-positive (OR of 0.15). All the anti-HDV-positive patients had mild fibrosis (F0–F1). Conclusions: Our study demonstrated an anti-HDV prevalence of 5.63% among adult Omani patients with chronic HBV infection, while active viremia appeared to be rare. Blood transfusions were the main identified risk factor. Given the very low HDV viremia, targeted screening of higher-risk groups may be efficient. Full article

This study analyses all cases of acute hepatitis E diagnosed in a southern Romanian hospital from 2019 to 2023. Patients with positive anti-HEV IgM antibodies were included in three groups: group A1—96 patients with probable HEV infection and ALT levels over 2.5-fold the upper limit of normal (ULN); group A2—44 patients with probable HEV infection and ALT levels under 2.5-fold ULN; group B—43 patients with probable HEV coinfection with another hepatotropic virus. Between 2019 and 2023, 642 patients were diagnosed with acute viral hepatitis. Positive anti-HEV IgM antibodies were detected in 183 (28.5%) cases, HEV being the second most common cause of acute viral hepatitis. Patients from group A were older than those from group B (47.26 ± 15.13 years vs. 35.95 ± 14.83 years, p < 0.01). Patients from group A were less likely to present clinical features compared to those from group B: digestive symptoms (73.8% vs. 97.2%, p < 0.01), jaundice (38.9% vs. 88.4%, p < 0.01), hepatomegaly (64.1% vs. 88.6%, p = 0.02). Patients from group A, compared to patients from group B, had lower levels of ALT (18.2 ± 29.9 ULN vs. 83.7 ± 56.2 ULN, p < 0.01) and total bilirubin (3.08 ± 5.2 mg/dL vs. 7.82 ± 5.25 mg/dL, p < 0.01) at admission. Patients from group A had higher levels of anti-HEV IgM antibodies (4.3 ± 3.22 vs. 2.55 ± 1.34, p < 0.01) than those from group B. Nearly all patients had no history of travel; therefore, autochthonous origin of HEV is involved in a large majority of cases. Currently, hepatitis E virus is not an uncommon aetiology of acute hepatitis in Romania, more often in adults and elderly patients. The epidemiological and clinical features of HEV infections plead for a zoonotic transmission in most cases. The significant number of cases of hepatitis E diagnosed in a single centre in Bucharest justifies the need to include early testing for HEV in patients with acute hepatitis. Full article

Background/Objectives: Adults aged 19–59 with diabetes are recommended by the Advisory Committee on Immunization Practices (ACIP) to receive vaccination against Hepatitis B Virus (HBV) infection because of their increased risk of contracting HBV. This study aimed to examine hepatitis B (HepB) vaccination rates among U.S. adults aged 19–59 years with diabetes and explore sociodemographic factors associated with HepB vaccination. Methods: Data from the 2015–2018 National Health and Nutrition Examination Survey (NHANES) were analyzed to compare HepB vaccination between adults with and without diabetes. Weighted Chi-square analysis was used to test the associations between HepB vaccination status and various categorical variables. Weighted logistic regression was employed to identify factors associated with being fully vaccinated. Results: A total of 5988 adults aged 19–59 were included in the study, of whom 504 (8.4%) had diabetes. The HepB vaccination rate was 32.3% for those with diabetes vs. 43.6% for those without diabetes (p = 0.01). However, after adjusting for other covariates, having diabetes was not associated with being fully vaccinated against HBV (p = 0.583). Adults aged 45–59 years were less likely to be vaccinated against HBV compared to those aged 19–29 (OR: 0.12, p < 0.0001). Having health insurance, being female, and having a higher educational level were all associated with HepB vaccination status (all p < 0.01). Overall, the HBV infection rate was 1.1%. Having HepB vaccination was associated with a lower risk of HBV infection among both groups with and without diabetes. Conclusions: HepB vaccination among U.S. adults with diabetes was suboptimal and lower than among those without diabetes. Age and education were associated with being fully vaccinated against HBV. Future research is needed to identify and better understand barriers to receiving HepB vaccines. Full article

Virus-associated hepatocellular carcinoma (HCC) remains a major global health burden despite effective antiviral therapies. Chronic infection with hepatitis B (HBV), hepatitis C (HCV), and hepatitis D (HDV) promotes malignant transformation through overlapping pathways of fibrosis, immune dysregulation, and microenvironmental remodeling. YKL-40, a glycoprotein secreted by hepatic stellate cells, hepatocytes under stress, macrophages, and endothelial cells, has emerged as a marker that reflects stromal activation rather than direct hepatocyte injury. Its expression is reinforced by profibrotic and angiogenic circuits, and circulating concentrations correlate with advanced fibrosis, residual risk after viral suppression, and oncologic outcomes. This review synthesizes current evidence on YKL-40 across HBV, HCV, and HDV cohorts, with emphasis on its role in bridging molecular mechanisms to clinical applications. We examine its utility in non-invasive fibrosis assessment, longitudinal monitoring after antiviral therapy, and prognostic modeling in HCC. Particular attention is given to its potential in the liver transplant pathway, where YKL-40 may refine eligibility beyond morphology, inform bridging therapy response, and predict post-transplant recurrence or graft fibrosis. Remaining challenges include its lack of disease specificity, assay variability, and limited multicenter validation. Future integration of YKL-40 into multimarker, algorithm-based frameworks could enable risk-adaptive strategies that align surveillance and transplant decisions with the evolving biology of virus-associated liver disease. Full article

Background/Objectives: Hepatitis B virus (HBV) remains a persistent challenge for transfusion safety. Although testing for hepatitis B surface antigen (HBsAg) and nucleic acid testing (NAT) reduces transmission risk, antibodies to hepatitis B core antigen (anti-HBc) and antibodies to hepatitis B surface antigen (anti-HBs) provide additional insight into past infection and vaccine-induced immunity. We aimed to determine their seroprevalence among blood donors in southern Croatia and assess associations with age, occupation, and time since vaccination. Methods: This cross-sectional study was conducted between February and November 2024 at two regional transfusion centers in southern Croatia. A total of 1008 voluntary blood donors, all HBsAg- and NAT-negative, were tested for anti-HBc and anti-HBs using chemiluminescent microparticle immunoassay. Demographic and vaccination data were collected through verified medical records. Results: Anti-HBc was detected in 0.5% of donors, exclusively among the unvaccinated. Protective anti-HBs levels were found in 38.1% overall and 70.6% of vaccinated donors, with significant declines by age and more than 15 years post-vaccination (p = 0.024). Healthcare workers showed higher seroprotection than non-healthcare donors (67.0% vs. 35.1%; p < 0.001), although one-third still lacked protective levels. Conclusions: HBV exposure was rare, but waning vaccine-induced immunity was evident, with protective anti-HBs levels in 70.6% of vaccinated donors, declining with age and time since vaccination. These findings highlight the need for periodic monitoring of anti-HBs and targeted booster strategies, especially in older and occupationally exposed groups. HBsAg and NAT provide a high level of transfusion safety, while the role of routine anti-HBc testing in this low-endemic context should be carefully evaluated in view of its potential benefits and drawbacks. Donor-based surveillance is a valuable tool for evaluating long-term vaccine effectiveness and guiding public health policy. Full article

Knowledge gaps exist regarding foodborne zoonotic diseases in migrant populations. We assessed the seroprevalence of Campylobacter, Salmonella, Yersinia, Brucella, hepatitis E virus (HEV), and Trichinella, and identified potential exposure risks in populations with and without migration backgrounds. In a cross-sectional study (2014–2016), adults with Turkish, Russian, Vietnamese, or German backgrounds residing in Berlin, Germany, were recruited via convenience sampling. Sera were screened for anti-IgG antibodies, and risk factors were assessed via a structured questionnaire. Logistic regression was used for analysis. We included 1180 participants: 497 Germans and 215, 273, and 195 individuals with Russian, Turkish, and Vietnamese backgrounds, respectively. Salmonella seroprevalence was highest among Vietnamese (47–50%) and lowest among Turks (18–20%). Campylobacter seroprevalence ranged from 17% to 23%. Yersinia seroprevalence was highest among Germans (64–70%) and associated with raw pork consumption. HEV seropositivity was highest among Vietnamese (27–28%) and lowest among Russians (5%). No samples were positive for Brucella; two were positive for Trichinella. High seroprevalence of Campylobacter, Salmonella, Yersinia, and HEV suggests substantial exposure and frequent asymptomatic or mild infections. While Yersinia seropositivity was associated with raw pork consumption, high seroprevalence in Turks—who rarely consume pork—suggests other food sources or transmission routes. Full article

Chronic hepatitis B virus (HBV) infection remains a major global health challenge, substantially contributing to liver-related morbidity and mortality. Background/Objectives: Developing therapeutic strategies that overcome immune tolerance and achieve functional cures is an urgent priority. Methods: In this study, we report a therapeutic vaccine comprising hepatitis B surface antigen (HBsAg) formulated with the dual adjuvant system CpG 1018S and QS-21. The immunogenicity and therapeutic efficacy of this vaccine were systematically evaluated in an rAAV8-HBV1.3-established chronic HBV mouse model. Results: The vaccine elicited a robust Th1-skewed immune response, characterized by elevated anti-HBs IgG2b titers and an increased IgG2b/IgG1 ratio. Notably, immunized mice showed markedly reduced circulating HBsAg levels. Mechanistically, the CpG 1018S and QS-21 adjuvant system enhanced dendritic cell activation, maturation, and antigen presentation, expanded HBV-specific CD4⁺ and CD8⁺ T cell populations, and attenuated the expression of the exhaustion markers TIM-3 and TIGIT. Additionally, immunized mice exhibited restored T cell polyfunctionality, with an increased secretion of effector cytokines, including TNF-α and IL-21. These responses collectively contributed to the reversal of T cell exhaustion and breakdown of immune tolerance, facilitating sustained viral suppression. Conclusions: Our findings demonstrate that the CpG 1018S/QS-21-adjuvanted vaccine induces potent humoral and cellular immunity against chronic HBV infection and represents a promising candidate for clinical chronic HBV (CHB) treatment. Full article

Background: The quest for well-defined immunoadjuvants remains one of the highest priorities for the successful development of effective vaccines. Combination adjuvants, which are designed to integrate both the ability to activate a variety of immune mechanisms and synergistically improve the delivery of vaccine components, are well-positioned to address the unmet needs. The development of a preventive vaccine against hepatitis C virus (HCV)—a major public health concern—is a particular instance in which the choice of the immunoadjuvant is of utmost importance. Methods: We assembled a lipid A Toll-like receptor 4 (TLR4) agonist BECC438 and TLR7/8 agonist resiquimod (R848) on a polyphosphazene macromolecule (PCPP) to create a nanoscale immunoadjuvant-vaccine delivery system: PCPP-R+BECC438. This aqueous-based system was formulated with the HCV sE2 antigen, and the resulting vaccine candidate was evaluated in vivo for the ability to induce immune responses. Results: Co-assembly of adjuvants resulted in a visually clear aqueous system of nanoscale dimensions, monomodal size distribution, and entropy-driven interactions between components. Intramuscular immunization of mice with HCV sE2 antigen formulated in a polyphosphazene-based nano-system induced ten-fold higher IgG and IgG2a titers than the antigen adjuvanted with BECC438 alone. PCPP-R+BECC438 formulated HCV sE2 also produced statistically significant improvements in IgG2a/IgG1 ratio and more robust HCVpp neutralization ID₅₀ titers than control formulations. Conclusions: Polyphosphazene-assembled adjuvant nano-system promotes in vivo immune responses of enhanced quantity and quality of antibodies with increased potency of HCV neutralization. Full article

Background: The hepatitis A virus (HAV) is a major cause of acute viral hepatitis and a significant global health concern. This study provides a pre-vaccination baseline for Oman, enabling longitudinal comparison with post-hepatitis A vaccination cohorts. This study aimed to determine the pre-vaccination seroprevalence of HAV antibodies (anti-HAV) in Oman and explore the associated demographic factors. Methods: A cross-sectional study was conducted from April 2014 to August 2015 among patients attending the medical outpatient clinic of the Medical City Hospital for Military and Security Services. Demographic data were collected via a structured questionnaire, and serum samples were tested for anti-HAV immunoglobulin IgG and IgM using enzyme-linked immunosorbent assays. Multivariate analysis was performed to identify the predictors of anti-HAV seroprevalence. Results: Among 1975 participants, 88.1% were positive for anti-HAV IgG. The mean age was 37.4 ± 16.1 years; however, those negative for anti-HAV IgG were considerably younger (mean age: 24.8 ± 15.7 years). Anti-HAV IgG seroprevalence was 37% in individuals aged ≤18 years and 91% in those >18 years (p < 0.001). The factors associated with seropositivity included older age (p < 0.001), consuming food prepared outside the home (p < 0.001), occupation (p < 0.001), and education level (p = 0.003). In the multivariable analysis, only age showed a strong independent association with serostatus: per 10-year increase, the aOR for anti-HAV IgG seropositivity was 2.87 (95% CI 2.25–3.63; p < 0.001). Conclusions: Our study estimates show high anti-HAV IgG seroprevalence and serve as a pre-vaccination baseline for evaluating the hepatitis A vaccination program in Oman over time. Given the lower natural exposure among younger cohorts, continued routine vaccination, scheduled serosurveys, and strengthened surveillance are required to identify emerging immunity gaps and prevent future HAV outbreaks. Full article

Background and Objectives: Hepatitis C virus (HCV) infection is highly prevalent among patients undergoing chronic hemodialysis in emerging countries and is associated with significant morbidity and mortality in this population. The objective of this study was to eradicate chronic HCV infection in patients undergoing chronic hemodialysis in Mauritania using a combination of sofosbuvir, 400 mg, and daclatasvir, 60 mg (direct acting antiviral—DAA—therapy), for 3 months. This was a prospective, single-arm, multicenter, interventional study. Materials and Methods: A total of 553 patients undergoing hemodialysis were screened for HCV across all hemodialysis centers nationwide. Biological parameters were compared before and after DAA therapy. Results: The prevalence of HCV infection was 6.8% (n = 38); two patients had undetectable HCV RNA. Out of the 36 eligible patients, 33 received DAA treatment. The median age of the patients was 49 (25–78) years. The average duration on hemodialysis was 9.4 (4–17) years. The median viral load before treatment was 538277 (10–4258571) IU/L. The median alanine aminotransferase (ALT) level was 52.3 (14–278) IU/L. The median hemoglobin level was 10 (6–13) g/dL. HCV viral load was undetectable at week 12 (W12) and week 24 (W24). The sustained virologic response (SVR) rate was 100%. Adverse events included one case of acute pancreatitis, six cases of fatigue (17%), five cases of headache (15%), four cases of diarrhea (12%), three cases of nausea (9%), and four cases of insomnia (12%). Conclusions: The combination of sofosbuvir and daclatasvir is effective in patients with HCV undergoing chronic hemodialysis, achieving a 100% SVR rate. Full article

Organ transplantation significantly enhances the survival and quality of life for recipients. However, multiple dependent and independent variables can adversely affect life expectancy after transplantation. Cancer is one of the most common causes of morbidity and mortality for long-term organ transplant recipients. The incidence of cancer in transplanted tissues can be twice as high in approximately 32 distinct cancer types. Oncogenic viruses present in graft tissues may contribute to the etiology of various cancers in transplant recipients. Such oncogenic viruses include hepatitis viruses, papillomaviruses, Epstein–Barr virus, Kaposi’s sarcoma, Merkel cell virus, JC virus, BK virus, and human T-lymphotropic virus type 1, all of which have been associated with various malignancies in these patients. To mitigate this risk, a comprehensive viral screening protocol should be integrated into the transplantation process. Depending on the type of graft, diagnostic methods, control strategies, and post-transplantation care may vary considerably. To efficiently implement any strategy to inhibit viral oncogenicity, a comprehensive understanding of viral–host interactions involving oncogenic viruses within graft tissue is essential. The current view of tumor biology is that changes in the tumor microenvironment and immune signaling influence evolutionary selection pressures. Such interactions ultimately promote conditions that favor uncontrolled host–cell proliferation and malignant transformation. This review examines these viral–host interactions and their role in cancer development among transplant recipients. Full article

New York State and New York City (NYC) developed hepatitis C (HCV) elimination plans to reduce premature deaths and new infections. NYC Health + Hospitals (NYC H + H), the municipal healthcare system for NYC serving over a million individuals annually, designed electronic health record (EHR) tools that collaboratively facilitated screening, linkage, and tracking of patients diagnosed with HCV through to cure. This study reviews the impact of this group of EHR tools by comparing data on HCV testing, linkage, and cure for 12 months before tools were released and a second 12-month period coinciding with the release of tools. Indicators related to HCV screening, diagnoses, treatment initiation, and cure were assessed. All indicators reviewed improved following the implementation of EHR tools. The proportion of individuals screened increased from 34% pre-intervention to 46% during the implementation phase; the number of individuals on direct-acting antivirals increased by 11%; and the number of individuals reaching cure increased by 37%. Efforts to collaboratively develop custom interlinking EHR tools to establish a systematic process proved impactful. Integrating the needs and functions of different care settings and the structure of the local epidemic allowed for the successful development and implementation of impactful resources. Full article

Duck viral hepatitis, caused by Duck Hepatitis A Virus Type 3 (DHAV-3), remains a major threat to young ducklings. Although DHAV-3 has circulated in China since the 1999s, the complete genomic architecture, exact virulence parameters, and evolutionary distance between early Yunnan isolates and current field strains have remained undefined. This study investigated six DHAV-3 strains isolated in Yunnan Province, China, between 2004 and 2006, to elucidate their genetic and biological characteristics. Full-genome sequencing and phylogenetic analysis revealed >99.5% nucleotide and >99.6% amino acid identity among the strains, suggesting a common ancestral origin. In vivo challenge assays showed rapid onset of clinical signs and >90% mortality in ducklings within 36 h post-inoculation. Embryonic deaths began at 24 h post-infection and peaked by 90 h. Viral replication was efficient in DEF, DEK, Vero, and BHK-21 cells, but absent in chicken fibroblasts (DF-1). Comparative genomic analysis between the YN/LR/2005 strain and recent field isolates (2022–2024) revealed substantial nucleotide divergence in structural regions, with 32 unique amino acid substitutions—all five located in the immunodominant VP1 region that may influence viral antigenicity and host interaction—alongside changes in N-glycosylation sites and alterations in protein secondary structure. Histopathological examination confirmed characteristic hepatic lesions. These findings demonstrate that while DHAV-3 has undergone genetic evolution, it retains high virulence, underscoring the need for ongoing molecular surveillance and supporting future vaccine and diagnostic development. Full article