Search Results (67)

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

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

If the number of viral hepatitis infections is to be decreased worldwide, and the World Health Organization (WHO) elimination targets are to be achieved by 2030, this requires determining the burden of infection according to the WHO’s test-and-treat approach. In 2014, the introduction of Direct-Acting Antivirals (DAAs) revolutionized the management of Hepatitis C Virus (HCV); another improvement came in 2020, when the use of bulevirtide (BLV) was authorized as a treatment for chronic Hepatitis D Virus (HDV) infection, showing good efficacy. The present observational study was carried out between 2019 and 2024. The diagnosis of viral hepatitis was carried out by routine assays. HDV typing was performed by Sanger sequencing and phylogenetic analysis. Overall, the HCV antibody prevalence was 3.4% in the studied time span, and it was higher in males than in females (59% vs. 41%). In viremic patients, HCV1b (33%) and HCV2a/2c (25%) were the most common subtypes. The overall HCV viremic rate declined in 2022 (2.8%). Unlike HCV, 71.4% of HDV viremic patients were females, and they had a median age of 58 years. The viral load of HDV RNA ranged from 20 IU/mL to 8 million IU/mL. Viral genotypes were classified as HDV1c and HDV1e. In this study, we highlight the prevalence of HCV/HDV infections and their genotype evolution in Southern Italy, underscoring the urgent need to enhance screening and linkage to care. Finally, we quantify the burden of active infections in order to provide data from real-life settings, and we describe the virological status of people living with HCV or HBV/HDV, who may experience significant benefits in terms of liver-related mortality after DAA or BLV treatment. Full article

The hepatitis D virus (HDV) is a small, defective RNA virus that induces the most severe form of viral hepatitis. Despite its severity, HDV infections are under-diagnosed due to non-standardized and costly diagnostic screening methods. However, limited research has been conducted on characterizing HDV-specific antibodies as alternative tools for diagnosis. Thus, we generated HDV-specific, polyclonal antibodies by immunizing rabbits with the HDV protein, small hepatitis delta antigen (SHDAg), in its oligomeric or denatured form. We identified SHDAg-specific linear epitopes by peptide array analysis and compared them to epitopes identified in HDV-infected patients. Using in silico structural analysis, we show that certain highly immunogenic domains in SHDAg, such as the coiled-coil domain, are masked in the oligomeric conformation of the protein; others, such as the second arginine-rich motif, are exposed. The nuclear localization signal is presumably exposed only by specific interaction of oligomeric HDAg with the HDV-RNA genome. Through surface plasmon resonance analysis, we identified two polyclonal antibodies derived from rabbit antisera with affinities in the lower nanomolar range. These antibodies were used to establish an ELISA that can quantitatively detect HDV virions in vitro and upon further optimization could be used as a promising alternative diagnostic screening method. Full article

Hepatitis D virus (HDV) infection remains a major cause of severe liver disease among hepatitis B virus (HBV)-infected patients, contributing to accelerated progression to cirrhosis and hepatocellular carcinoma. Pegylated interferon-α remains the first-line therapy for chronic HDV infection in most cases. However, despite its approval for HBV and hepatitis C virus (HCV) infections, its use in HDV is largely driven by a lack of other options and is constrained by its limited efficacy, suboptimal durability of response, and a substantial side effect profile. Meanwhile, bulevirtide, an entry inhibitor, became the first agent to be approved for use in chronic HDV infections by the European Medicines Agency (EMA), and several other therapies are currently being investigated as well. In this review, we provide updates on recent advancements in HDV treatment and novel therapies. Full article

Chronic hepatitis B (HBV), alongside hepatitis D virus (HDV) super-/co-infection and chronic hepatitis C (HCV), are major contributors to cirrhosis, end-stage liver disease, hepatocellular carcinoma (HCC), and liver-related mortality. Despite significant progress in antiviral treatments and HBV vaccination, viral hepatitis remains a global health burden. Vulnerable populations, such as those experiencing homelessness, migrants, and economically disadvantaged groups, are disproportionately impacted by these infections, often facing barriers to care and exclusion from traditional health systems. This leads to undiagnosed cases and ongoing transmission, undermining global efforts to eliminate HBV and HCV by 2030, as outlined by the World Health Organization (WHO). Recent studies highlight the importance of tailored interventions to address health inequalities. For instance, on-site community-based screening initiatives targeting marginalized groups have shown promise, achieving higher linkage to care rates without monetary incentives. These approaches not only enhance diagnosis but also facilitate integration into healthcare systems, addressing both public health and social disparities. This review underscores the need for targeted strategies to promote the early detection and management of HBV and HCV in underserved populations. Such efforts are critical to advancing the WHO’s elimination goals, improving health outcomes, and addressing the broader social determinants of health. Full article

Background: Hepatitis D virus (HDV) is a defective virus requiring co-infection with hepatitis B virus (HBV) to replicate, occurring in 5% of HBV+ patients. Bulevirtide (BLV) is now the first-in-class specific anti-HDV agent, inhibiting HDV binding to NTCP, with good tolerability and good virological and biochemical response rates. Currently, little is known about its pharmacokinetic/pharmacodynamic (PK/PD), as well as potential drug-drug interaction (DDI) profile. In this work we provide a systematic review of the current knowledge on these aspects. Methods: A literature review of PK, PD and DDI profiles of BLV was conducted from Pubmed and EMA websites. Experimentally tested interactions and hypothetical mechanisms of interaction were evaluated, mostly focusing on usually co-administered anti-infective agents and other drugs interacting on NTCP. Results: BLV shows non-linear PK, due to target-mediated drug disposition, so its PK as well as PD is expected to be influenced by interactions of other drugs with NTCP, while it is not substrate of CYPs and ABC transporters. In-vivo investigated DDIs showed no clinically relevant interactions, but a weak inhibitory effect was suggested on CYP3A4 in a work when used at high doses (10 mg instead of 2 mg). In vitro, a weak inhibitory effect on OATP transporters was observed, but at much higher concentrations than the ones expected in vivo. Conclusions: The drug-drug interaction potential of BLV can be considered generally very low, particularly at the currently approved dose of 2 mg/day. Some attention should be paid to the coadministration of drugs with known binding and/or inhibition of NTCP. Full article

Introduction: Hepatitis D virus (HDV) infection remains a significant global health challenge due to its severity and high risk of progression to cirrhosis and hepatocellular carcinoma (HCC). Bulevirtide, a novel HDV entry inhibitor, has shown promise in managing chronic hepatitis D by blocking viral entry into hepatocytes. This study evaluated the efficacy and safety of bulevirtide in reducing HDV RNA levels and improving liver function in a real-life cohort of Italian patients with HDV infection. Methods: This multicenter prospective trial enrolled 108 consecutive patients with chronic HDV infection, from June 2023 to June 2024, who received 2 mg/day of bulevirtide in combination with a nucleoside/nucleotide analogue for hepatitis B virus (HBV) infection. Patients with any stage of liver fibrosis or compensated cirrhosis were included. Data collected included demographic and clinical characteristics, liver function tests, HDV RNA levels, and adverse events at baseline and 6 months. Results: The virological response was achieved in 54.6% of patients (n = 59), with 36 demonstrating undetectable HDV RNA levels. Among responders, ALT levels decreased significantly from 67.0 U/mL [IQR 44.0–116.3] to 31.5 U/mL [IQR 24.0–36.5, p = 0.001], and AST levels from 66.0 U/mL [IQR 46.5–91.0] to 32.5 U/mL [IQR 28.0–38.0, p = 0.021]. Median HDV RNA dropped from 29,800 IU/mL [IQR 3100–375,000] to 0 IU/mL [IQR 0–291, p < 0.001]. No significant predictors of response emerged. Mild adverse events, including pruritus (5.6%) and injection-site reactions (1.9%) and flu-like syndrome (0.9) were reported, with no treatment discontinuation. Conclusions: Bulevirtide effectively reduces HDV RNA levels and improves liver function with a favorable safety profile, offering a promising therapeutic option for chronic hepatitis D. Further large-scale studies are needed to confirm these findings and explore long-term outcomes. Full article

Information on circulating HBV (sub-)genotype, variants, and hepatitis D virus (HDV) coinfection, which vary by geographical area, is crucial for the efficient control and management of HBV. We investigated the genomic characteristics of HBV (with a prevalence of 8.1%) and the prevalence of HDV in Nigeria. We utilised 777 HBV-positive samples and epidemiological data from the two-stage sampled population-based, nationally representative Nigeria HIV/AIDS Indicator and Impact Survey conducted in 2018. We assessed 732 HBV DNA-extracted samples with detectable viral loads (VLs) for (sub-)genotypes and variants by whole-genome pre-amplification, nested PCR of the s-and pol-gene, and BigDye Terminator sequencing. We conducted HDV serology. In total, 19 out of the 36 + 1 states in Nigeria had a high prevalence of HBV (≥8%), with the highest prevalence (10.4%) in the north-central geopolitical zone. Up to 33.2% (95% CI 30.0–36.6) of the participants had detectable VLs of ≥300 copies/mL. The predominant circulating HBV genotype was E with 98.4% (95% CI 97.1–99.1), followed by A with 1.6% (95% CI 0.9–2.9). Drug-resistant associated variants and immune escape variants were detected in 9.3% and 0.4%, respectively. The seroprevalence of HDV was 7.34% (95% CI 5.5–9.2). Nigeria has subtype E as the major genotype with many variants. Full article

Background: The World Health Organization (WHO) recommends hepatitis D virus (HDV) screening among hepatitis B virus (HBV) infected individuals, with a focus on priority populations in resource-limited settings like Nigeria. HDV infection is a growing public health challenge, particularly among individuals with chronic hepatitis B virus (HBV) infection. HDV accelerates liver disease progression and significantly increases the risk of cirrhosis and hepatocellular carcinoma. Despite this, the epidemiology of HDV in Nigeria remains inadequately documented. This scoping review critically evaluates the prevalence, risk factors, and clinical outcomes of HDV co-infection among HBV patients in Nigeria. Method: We conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The review included observational cross-sectional studies published between 2009 and 2024. We focused on studies that used Immunoglobulin G (IgG) antibody testing or RNA-based diagnostics to assess HDV prevalence. We included PubMed, Google Scholar, and Dimensions databases due to their broad indexing and coverage of peer-reviewed articles and accessibility. We screened the studies for their relevance to HDV prevalence, risk factors, and clinical outcomes, while excluding those that only tested for IgM or HDV antigen. Eleven studies, with a combined sample size of 2308 participants, were included in the final analysis. We performed a narrative synthesis of the findings, considering geographic, gender, and age-based variations in HDV prevalence and clinical impact. Results: HDV prevalence among HBV-infected individuals in Nigeria ranged from 2.0% to 31.6%. The highest prevalence was reported in the Southwest (31.6%) among malaria patients, while lower rates were observed in the Southeast (2.8%). Prevalence was higher in males, particularly those aged 21–30 years in the Southwest and 31–40 years in other regions. RNA-based testing provided more accurate data on active viremia, with viremic HDV prevalence rates ranging from 3.2% to 16%. Triple infection with HIV/HBV/HDV was associated with significantly lower CD4+ cell counts and worse clinical outcomes, including elevated liver enzymes and rapid progression to liver cancer. Key risk factors for HDV co-infection included multiple sexual partners, sharing of needles, and unsafe medical practices. Co-infected patients demonstrated worse clinical outcomes, such as elevated liver enzymes, decompensated cirrhosis, and higher rates of hepatocellular carcinoma. Conclusions: Our review underscores the urgent need for routine HDV screening among HBV patients in Nigeria, especially given the severe clinical consequences of co-infection. The recent WHO guidelines recommending HDV screening align with our findings, which emphasize the importance of RNA-based HDV testing among HBV-positive patients to improve diagnostic accuracy. Public health efforts should prioritize tailored interventions based on geographic, age, and gender disparities in HDV prevalence. Triple infection with HIV/HBV/HDV requires integrated care models to address both immune suppressions as indicated by diminished CD4 cell count and liver disease progression, as these patients face worse outcomes. Targeted HDV screening in mostly affected demographics and geographies and improved Nigeria capacity for cheaper HDV RNA/PCR diagnostics can reduce liver-related morbidity and mortality caused by HBV, which can be worsened and accelerated by HDV coinfection. Full article

More than 12 million individuals worldwide are chronically infected with the hepatitis D virus (HDV). HDV infection is the most severe form of viral hepatitis since it requires hepatitis B virus co-infection and accelerates progression to cirrhosis and hepatocellular carcinoma. Therefore, treatment modalities to slow the progression of the disease are essential but not yet available. In addition, no antiviral treatment to date has been shown to reliably eradicate HDV. Pegylated interferon (PEG-IFN) is the only universally used treatment to suppress HDV RNA replication and improve liver inflammation and fibrosis. This treatment can be completed in 12–18 months, but cure rates remain low, and success does not reliably increase with the addition of a nucleos(t)ide analog. PEG-IFN therapy is also limited by poor tolerability and multiple adverse effects, including neutropenia, thrombocytopenia, and neuropsychiatric symptoms. Newer antiviral therapies in development target unique aspects of HDV viral replication and show promising results in combination with PEG-IFN for long-term HDV RNA suppression. These newer antiviral therapies include buleviritide (which blocks HDV entry), lonafarnib (which prevents HDV assembly), and REP-2139 (which prevents HDV export). In this manuscript, we discuss the characteristics of HDV infection and review the new antiviral therapies approved for treatment and those under investigation. Full article

Hepatitis delta virus (HDV) co-infections more often result in severe hepatitis compared to hepatitis B virus (HBV) infections alone. Despite a high HDV prevalence (7.1%), information regarding circulating HDV clades is very limited in Botswana. We extracted total nucleic acid from confirmed HDV-positive samples and quantified their viral load. We then sequenced the large hepatitis delta antigen (L-HDAg) using Oxford Nanopore Technology (ONT). Genotyping was performed using the HDV Database, and HDV mutation profiling was performed on AliView. All participants with HBV genotypic information belonged to sub-genotype A1, and 80% (4/5) of them had a higher HDV viral load and a lower HBV viral load. We sequenced 75% (9/12) of the HDV-positive samples, which belonged to HDV clade 8. A total of 54 mutations were discovered, with the most prevalent being Q148R (16%), D149P (16%) and G151D (16%). Known mutations such as S117A, K131R, R139K and G151D were detected, while the other mutations were novel. Our results reveal that HDV clade 8 is the predominant clade in Botswana. The significance of all mutations remains unclear. Future studies with a larger sample size to detect other HDV clades that might be circulating in Botswana and functionally characterize the detected mutations are warranted. Full article

The hepatitis D virus (HDV) superinfection of individuals with chronic hepatitis B virus (HBV) infection causes severe liver damage and the poorest long-term prognosis among viral hepatitis. This is attributed to the unique pathogenic mechanisms of HDV characterized by a direct cytopathic effect on hepatocytes and a significant impairment of the host immune response. The HDV genotype largely influences the extent of the pathogenic mechanisms with consequences on disease progression towards cirrhosis, liver decompensation, or hepatocellular carcinoma. In this context, identifying the circulating HDV genotypes in European regions with high prevalence, such as Romania, is crucial for effectively managing the long-term liver health. Here, we report the first comprehensive HDV study in Romania that clinically characterizes 82 patients and performs HDV genotyping by combining the nested-PCR reaction with sequencing analysis in 49 samples with an HDV-RNA load higher than 5000 IU/mL. While all isolates in our study belong to the HDV-1 genotype, the phylogenetic analysis based on sequence data from GenBank reveals the presence of the following potential three groups: (i) Italy and France; (ii) Spain; and (iii) Turkey, Iran, Pakistan, and Germany. This broad clustering highlights the recent surge in migration to and from Western Europe and the Middle East. Equally important, no differences in viral markers, clinical and paraclinical parameters, or treatment options were observed between these identified clusters. Nevertheless, this study considerably advances the understanding of hepatitis D epidemiology and clinical aspects in Romania. Full article

The interaction of multiple viruses in one host is thought to enhance the development of mutations. However, the impact of hepatitis D virus (HDV) positivity on the development of unique hepatitis B virus (HBV) mutations among people living with human immunodeficiency virus (HIV) (PLWH) remains poorly understood in African countries, including Botswana. We used HBV sequences generated from the Botswana Combination Prevention Project (BCPP), which is the largest pair-matched cluster-randomized HIV trial in Botswana. Only participants with available HBV sequences (n = 55) were included in our study ([HIV/HBV-positive (n = 50) and HIV/HBV/HDV-positive (n = 5)]. Geno2pheno was used to determine HBV genotypes, and HBV surface region sequences (all subgenotype A1) were aligned in AliView for mutational analysis, while the impact of mutations was assessed using Phyre2. Our results identified 182 common mutations between the two groups. In the HIV/HBV/HDV cohort, only three mutations (L95W, W156Q, C221Y) were classified as deleterious, with only L95W being the most frequent. In the HIV/HBV cohort, four mutations (W199R, C221A, C221S, W223G) were also classified as deleterious. Our results demonstrate the presence of unique HBV mutations among the HIV/HBV/HDV-positive cohort. Functional characterization of these mutations is recommended to determine their effect on HDV. Full article