Search

Recent advances in studies exploring the roles of extracellular vesicles (EVs) in viral transmission and replication have illuminated hepatotropic viruses, such as hepatitis A (HAV), hepatitis B (HBV), hepatitis C (HCV), hepatitis D (HDV), and hepatitis E (HEV). While previous investigations have uncovered these viruses' ability to exploit cellular EV pathways for replication and transmission, most have focused on the impacts of exosomal pathways. With an improved understanding of EVs, four main subtypes, including exosomes, microvesicles, large oncosomes, and apoptotic bodies, have been categorized based on size and biogenic pathways. However, there remains a noticeable gap in comprehensive reviews summarizing recent findings and outlining future perspectives for EV studies related to hepatotropic viruses. This review aims to consolidate insights into EV pathways utilized by hepatotropic viruses, offering guidance for the future research direction in this field. By comprehending the diverse range of hepatotropic virus-associated EVs and their role in cellular communication during productive viral infections, this review may offer valuable insights for targeting therapeutics and devising strategies to combat virulent hepatotropic virus infections and the associated incidence of liver cancer. [ABSTRACT FROM AUTHOR]

Duck hepatitis A virus type 1 (DHAV-1) is an important member of the Picornaviridae family that causes highly fatal hepatitis in ducklings. Since picornaviruses have small genomes with limited coding capacity, they must utilize host proteins for viral cap-independent translation and RNA replication. Here, we report the role of duck poly(rC)-binding protein 2 (PCBP2) in regulating the replication and translation of DHAV-1. During DHAV-1 infection, PCBP2 expression was upregulated. A biotinylated RNA pull-down assay revealed that PCBP2 positively regulates DHAV-1 translation through specific interactions with structural domains II and III of the DHAV-1 internal ribosome entry site (IRES). Further studies revealed that PCBP2 promotes DHAV-1 replication via an interaction of its KH1 domain (aa 1–92) with DHAV-1 3Dpol. Thus, our studies demonstrated the specific role of PCBP2 in regulating DHAV-1 translation and replication, revealing a novel mechanism by which host‒virus interactions regulate viral translation and replication. These findings contribute to further understanding of the pathogenesis of picornavirus infections. [ABSTRACT FROM AUTHOR]

Background: Hepatitis A virus (HAV) infection is a significant global cause of viral hepatitis. At present, the anti-HAV vaccine in Italy is proposed exclusively for specific high-risk groups, and a universal vaccination program is not implemented. Objectives: This study aimed to assess the level of immunity against HAV in patients of both sexes across age groups ranging from 0 to 95 years admitted to the San Giovanni di Dio e Ruggi d'Aragona Hospital in Salerno, Italy, over a 9-year period (2015–2023). Methods: The total HAV seroprevalence by chemiluminescence Vitros system immunodiagnostics (ortho-diagnostics) was obtained by database analysis, stratifying patients for gender and age group in both the pre-pandemic (2015–2019) and pandemic (2020–2023) periods. Results: Out of 28,104 samples collected in 2015–2023, 20,613 resulted positive by total HAV immune screening, with a significant reduction in the annualized proportion of events during the pandemic period compared to the pre-pandemic period. HAV was more abundant in males than females in both periods (exceeding the 70%), with a statistically significant decrease in HAV in females in 2015–2019. The 61–70-year-old age group is more susceptible for both genders, with a strong deviation from the 41–50-year-old age group compared to the 51–60-year-old group. The pandemic period affected the number of analyzed samples in 2020. Conclusions: The study revealed high HAV seroprevalence, especially in males and individuals aged 61–70 years. There was a notable decrease in seroprevalence during the pandemic compared to pre-pandemic years. These results emphasize the need for ongoing monitoring and suggest that a universal vaccination program could address regional immunity gaps and lower disease incidence. [ABSTRACT FROM AUTHOR]

Simple Summary: Duck hepatitis A virus (DHAV) is an infectious pathogen that causes fatal viral hepatitis in ducklings. Duck hepatitis A virus-1 (DHAV-1) is the most virulent and widely distributed serotype, inflicting severe damage on the global duck farming industry. The main approach to preventing DHAV-1 involves using attenuated live vaccines. However, these vaccine strains may persist in ducks and pose a risk of reverting to virulence. Therefore, distinguishing between infected and vaccinated animals is vital for clinical diagnosis and vaccine safety monitoring. Currently, only time-consuming and costly sequencing methods serve this purpose. In this study, a Mismatch Amplification Mutation Assay (MAMA)-PCR method was developed based on single nucleotide polymorphism (SNPs) in the VP1 gene. The MAMA-PCR method offers a highly specific and sensitive clinical tool for rapidly distinguishing DHAV-1 wild-type from vaccine strains, significantly contributing to accurate clinical diagnosis and epidemiological understanding. Duck hepatitis A virus type 1 (DHAV-1) is the main pathogen causing viral hepatitis in ducks, marked by high contagion and acute mortality. Live attenuated DHAV-1 vaccines are widely used to control the disease. This study aims to develop a mismatch amplification mutation assay (MAMA)-PCR for the rapid detection and differentiation of Korean DHAV-1 wild-type strains from vaccine strains. A MAMA primer was designed to target a single nucleotide polymorphism (SNPs) at position 2276 within the VP1 gene, allowing differentiation in a single PCR reaction. The MAMA-PCR accurately identified both strains, with detection limits of 100.5 ELD50/mL and 102.3 ELD50/mL, respectively. The MAMA-PCR demonstrated specificity, showing no cross-reactivity with 12 other viral and bacterial pathogens. The MAMA-PCR was applied to 89 farms, yielding results consistent with nested-PCR and sequence determination, identifying four positive farms for DHAV-1 vaccine strains. In conclusion, this study is the first to employ the MAMA-PCR method to distinguish between DHAV-1 wild-type and vaccine strains. The developed method is rapid, simple, specific, and sensitive, thereby serving as an effective tool for clinical diagnostics in identifying and differentiating between Korean DHAV-1 wild-type and vaccine strains. [ABSTRACT FROM AUTHOR]

Food contact surfaces can harbor and transmit pathogens leading to outbreaks. Decontamination strategies that are user- and environmentally-friendly without toxic by-product formation are needed. Novel UV-C light-emitting diode (LED) technologies are being explored to deliver the required dose to inactivate viruses in food-processing environments. The objective of this study was to compare the effects of 279 nm UV-C LED to 254 nm UV-C against hepatitis A virus (HAV) and feline calicivirus (FCV, a cultivable human norovirus surrogate) on stainless-steel, ceramic, and glass surfaces. Viruses were surface spread on sterile stainless-steel or ceramic coupons (100 μL on 2 × 2 cm2), or glass discs (50 μL on 1 × 1 cm2), air-dried, and UV-C-treated for up to 3.75 min (surface dose = 0–49.2 mJ/cm2 for HAV and 0–24.6 mJ/cm2 for FCV). Each triplicate treatment was assayed in duplicate, and data were statistically analyzed. The D10-values for HAV treated with UV-C at 254 nm on stainless-steel, ceramic, and glass were 9.48 ± 0.34, 14.53 ± 2.52, and 6.91 ± 1.93 mJ/cm2, while with UV-C LED at 279 nm were 19.53 ± 2.45, 26.05 ± 0.60, and 8.77 ± 2.08 mJ/cm2, respectively. The D10-values for FCV treated with UV-C at 254 nm on stainless-steel, ceramic, and glass were 3.65 ± 0.06, 6.25 ± 1.90, and 4.69 ± 0.03 mJ/cm2, while with UV-C LED at 279 nm were 7.097 ± 2.11, 8.31 ± 2.12, and 7.88 ± 0.86 mJ/cm2, respectively. Higher 279 nm UV-C doses were needed to inactivate HAV and FCV compared to 254 nm UV-C on the tested surfaces. Novel UV-C LED systems using appropriate doses show promise to inactivate foodborne viruses on food contact surfaces. [ABSTRACT FROM AUTHOR]

Duck hepatitis virus 1 (DHV-1) is a major threat to the global poultry industry, causing significant economic losses due to high mortality rates in young ducklings. To better understand the evolution and host adaptation strategies of DHV-1, we conducted a comprehensive codon usage analysis of DHV-1 genomes. Our phylogenetic analysis revealed three well-supported DHV-1 phylogroups (Ia, Ib, and II) with distinct genetic diversity patterns. Comparative analyses of the codon usage bias and dinucleotide abundance uncovered a strong preference for A/U-ended codons and a biased pattern of dinucleotide usage in the DHV-1 genome, with CG dinucleotides being extremely underrepresented. Effective number of codons (ENC) analysis indicated a low codon usage bias in the DHV-1 ORF sequences, suggesting adaptation to host codon usage preferences. PR2 bias, ENC plot, and neutrality analyses revealed that both mutation pressure and natural selection influence the codon usage patterns of DHV-1. Notably, the three DHV-1 phylogroups exhibited distinct evolutionary trends, with phylogroups Ia and Ib showing evidence of neutral evolution accompanied by selective pressure, while the phylogroup II evolution was primarily driven by random genetic drift. Comparative analysis of the codon usage indices (CAI, RCDI, and SiD) among the phylogroups highlighted significant differences between subgroups Ia and Ib, suggesting distinct evolutionary pressures or adaptations influencing their codon usage. These findings contribute to our understanding of DHV-1 evolution and host adaptation, with potential implications for the development of effective control measures and vaccines. [ABSTRACT FROM AUTHOR]

Simple Summary: In the era of direct-acting antiviral (DAA) agents, chronic hepatitis C virus (HCV) infection has become a curable disease. Eradication of the virus remains a major goal for the World Health Organization (WHO) by 2030. Main obstacles seem to be the lack of national screenings and shortage of knowledge among patients and healthcare professionals. There also remain, scarcely described in the literature, specific groups of patients who, due to their comorbidities such as malignant tumors, may not be considered as candidates eligible for DAA treatment. In our study, we aimed to characterize and present treatment efficacy in individuals with chronic hepatitis C and an active malignancy treated in Poland in years 2015–2020 with DAAs and compare their outcomes with a treated population with no active malignancy. The obtained results indicate high effectiveness and a low number of premature treatment discontinuations for the majority of patients with active malignancies, with some concerns around HCCs. We believe that data provided by this study will lead to more efficient elaboration of the standard of care in this population. Background: Over the past years, the introduction of direct-acting antivirals (DAAs) revolutionized chronic hepatitis C treatment. We aimed to characterize and assess treatment efficacy in three specific groups of patients treated with DAAs: those with active solid malignant tumors (SMTs), hematological diseases (HDs) and hepatocellular carcinomas (HCCs). Methods: A total of 203 patients with active oncological disease (SMT n = 61, HD = 67, HCC n = 74) during DAA treatment in 2015–2020 selected from the EpiTer-2 database were analyzed retrospectively and compared to 12,983 patients without any active malignancy. Results: Extrahepatic symptoms were more frequent in HD patients (17.2% vs. SMT = 10.3%, HCC = 8.2%, without = 7.8%, p = 0.004). HCC patients characterized with the highest ALT activity (81 IU/L vs. SMT = 59.5 IU/L, HD = 52 IU/L, without = 58 IU/L, p = 0.001) more often had F4 fibrosis as well (86.11% vs. SMT = 23.3%, HD = 28.8%, controls = 24.4%, p = 0.001). A significant majority of subjects in HCC, HD and SMT populations completed the full treatment plan (HCC = 91%; n = 67, HD = 97%; n = 65, SMT = 100%; n = 62). Concerning the treatment efficacy, the overall sustained virologic response, excluding non-virologic failures, was reported in 93.6% HD, 90.16% SMT and 80.6% in HCC patients. Conclusions: As presented in our study, DAA therapy has proven to be highly effective and safe in patients with active SMTs and HDs. However, therapy discontinuations resulting from liver disease progression remain to be the major concern in HCC patients. [ABSTRACT FROM AUTHOR]

Background: Fulminant hepatitis is a rare and severe form of acute liver failure (ALF) characterized by rapid and massive destruction of liver cells and associated with a high mortality rate. Infectious factors, in particular viral hepatitis, take a prominent place in the etiology of ALF, however, the presence of chronic liver pathology can play a significant role in the disease progression and development of ALF. Case Presentation: A 2-year-old child was hospitalized on the 4th day of the disease with manifestations of jaundice and general intoxication. The examination revealed markers of active hepatitis A virus infection and Epstein-Barr virus infection. From the seventh day of the disease, the child's condition began to progressively deteriorate due to manifestations of ALF. Despite the use of immunomodulatory and replacement therapy, the disease ended fatally on the 9th day. Pathohistological examination revealed manifestations of viral necrotic hepatitis on the background of autoimmune sclerosing cholangitis. Conclusion: The case is novel as regards the occurrence of two viral hepatitis with different modes of transmission on a background of unidentified liver disease. [ABSTRACT FROM AUTHOR]

Hepatitis delta virus (HDV) infection is the most severe form of viral hepatitis. Genotype 1 (HDV-1) is by far the most prevalent in Europe and globally, while HDV-5 predominates in Western Africa. Data about HDV seroprevalence in Portugal are scarce and genotyping studies have not been performed yet. We aimed to assess the seroprevalence and genotypes of HDV in a large cohort of HBsAg-positive patients followed in our Hepatology Unit between 2012 and 2022. The anti-HDV-positive patients were subjected to a cross-sectional analysis, including blood sample collection for HDV RNA testing and genotype determination. In the cohort of HBsAg-positive patients, 57.5% (480/835) were born in African countries and 665/835 (79.6%) had been screened for anti-HDV antibodies. The HDV seroprevalence obtained was 6.5% (43/665). Twenty-one patients (age 41.2 ± 9.9 years; 57.1% male) were included in further molecular analyses. HDV RNA was positive in 8/21 (38.0%) and classified as HDV-5 in 7 patients (6 from Guinea-Bissau and 1 from Cape Verde) and HDV-1 in 1 patient (from Ukraine). In the largest and most comprehensive study performed in Portugal regarding HDV epidemiology to date, seroprevalence and genotype distribution of HDV (with predominance of HDV-5) were strongly influenced by immigration, notably from African countries. [ABSTRACT FROM AUTHOR]

Globally, waterborne viral infections significantly threaten public health. While current European Union regulations stipulate that drinking water must be devoid of harmful pathogens, they do not specifically address the presence of enteric viruses in water used for irrigation or food production. Traditional virus detection methods rely on molecular biology assays, requiring specialized personnel and laboratory facilities. Here, we describe an electrochemical sandwich enzyme-linked immunomagnetic assay (ELIME) for the detection of the hepatitis A virus (HAV) in water matrices. This method employed screen-printed electrodes as the sensing platform and utilized commercially available pre-activated magnetic beads to provide a robust foundation for the immunological reaction. The ELIME assay demonstrated exceptional analytical performance in only 185 min achieving a detection limit of 0.5 genomic copies per milliliter (g.c./mL) and exhibiting good reproducibility with a relative standard deviation (RSD) of 7% in HAV-spiked drinking and processing water samples. Compared with the real-time RT-qPCR method described in ISO 15216-1, the ELIME assay demonstrated higher sensitivity, although the overall linearity of the method was moderate. These analytical attributes highlight the potential of the ELIME assay as a rapid and viable alternative for HAV detection in water used for agriculture and food processing. [ABSTRACT FROM AUTHOR]

Viral hepatitis is a major cause of liver illness worldwide. Despite advances in the understanding of these infections, the pathogenesis of hepatitis remains a complex process driven by intricate interactions between hepatitis viruses and host cells at the molecular level. This paper will examine in detail the dynamics of these host–pathogen interactions, highlighting the key mechanisms that regulate virus entry into the hepatocyte, their replication, evasion of immune responses, and induction of hepatocellular damage. The unique strategies employed by different hepatitis viruses, such as hepatitis B, C, D, and E viruses, to exploit metabolic and cell signaling pathways to their advantage will be discussed. At the same time, the innate and adaptive immune responses put in place by the host to counter viral infection will be analyzed. Special attention will be paid to genetic, epigenetic, and environmental factors that modulate individual susceptibility to different forms of viral hepatitis. In addition, this work will highlight the latest findings on the mechanisms of viral persistence leading to the chronic hepatitis state and the potential implications for the development of new therapeutic strategies. Fully understanding the complex host–pathogen interactions in viral hepatitis is crucial to identifying new therapeutic targets, developing more effective approaches for treatment, and shedding light on the mechanisms underlying progression to more advanced stages of liver damage. [ABSTRACT FROM AUTHOR]

Abstract Recent advances in studies exploring the roles of extracellular vesicles (EVs) in viral transmission and replication have illuminated hepatotropic viruses, such as hepatitis A (HAV), hepatitis B (HBV), hepatitis C (HCV), hepatitis D (HDV), and hepatitis E (HEV). While previous investigations have uncovered these viruses’ ability to exploit cellular EV pathways for replication and transmission, most have focused on the impacts of exosomal pathways. With an improved understanding of EVs, four main subtypes, including exosomes, microvesicles, large oncosomes, and apoptotic bodies, have been categorized based on size and biogenic pathways. However, there remains a noticeable gap in comprehensive reviews summarizing recent findings and outlining future perspectives for EV studies related to hepatotropic viruses. This review aims to consolidate insights into EV pathways utilized by hepatotropic viruses, offering guidance for the future research direction in this field. By comprehending the diverse range of hepatotropic virus-associated EVs and their role in cellular communication during productive viral infections, this review may offer valuable insights for targeting therapeutics and devising strategies to combat virulent hepatotropic virus infections and the associated incidence of liver cancer.

Hepatitis C virus (HCV) chronically infects approximately 170 million people worldwide and is a known etiological agent of hepatocellular carcinoma (HCC). The molecular mechanisms of HCV-mediated carcinogenesis are not fully understood. This review article focuses on the oncogenic potential of NS3, a viral protein with transformative effects on cells, although the precise mechanisms remain elusive. Unlike the more extensively studied Core and NS5A proteins, NS3's roles in cancer development are less defined but critical. Research indicates that NS3 is implicated in several carcinogenic processes such as proliferative signaling, cell death resistance, genomic instability and mutations, invasion and metastasis, tumor-related inflammation, immune evasion, and replicative immortality. Understanding the direct impact of viral proteins such as NS3 on cellular transformation is crucial for elucidating HCV's role in HCC development. Overall, this review sheds light on the molecular mechanisms used by NS3 to contribute to hepatocarcinogenesis, and highlights its significance in the context of HCV-associated HCC, underscoring the need for further investigation into its specific molecular and cellular actions. [ABSTRACT FROM AUTHOR]

In 2023, passive laboratory-based surveillance showed an increase in hepatitis A virus (HAV) infection. We investigated hepatitis A incidence using the notifiable medical condition surveillance system (NMCSS) data and molecularly characterised positive blood samples from the Western Cape province for 2023. All HAV IgM seropositive cases from the NMCSS from 1 January to 31 October 2023 in South Africa were investigated. HAV RNA from blood samples that had tested positive for HAV IgM from Western Cape was amplified in the VP1/P2B junction and sequenced (3500Xl Genetic Analyser). Sequences were assembled, aligned (Sequencher) and analysed (Aliview 1.27 and MEGA11). Statistical analysis was performed using Excel and the CuSum2 Threshold to determine suspected outbreaks. In 2023, the incidence of HAV IgM was 6.28/100,000 in South Africa, with the highest incidence in Western Cape province (15.86/100,000). Children aged 5 to 14 years were affected the most in the Western Cape. The positive cases in the Western Cape were above the CuSum2 threshold from January to May 2023, with the highest incidence observed in the City of Cape Town Metropolitan (14.8/100,000). Genotyping was successfully performed on 92.7% (139/150) of serum samples, for which the IB sub-genotype was detected. Three primary mutations R63K, R71S and M104I were observed in more than 49% of the samples. Most of the samples sequenced belonged to patients residing in areas close to each other within the City of Cape Town Southern, Western, and Mitchells Plain sub-districts. The CuSum2 threshold method allowed the identification of suspected HAV outbreaks in the districts within the Western Cape in 2023 while genotyping identified clusters of sub-genotype IB. Genotyping could assist with determining the common source of infection during an outbreak, especially if coupled with epidemiological and geographical data. Further active surveillance can assist in investigating the HAV risk factors for targeted public health responses. [ABSTRACT FROM AUTHOR]

Background: Salivary gland neoplasms (SGNs) pose a challenge to both pathologists and clinicians. Despite research, the etiology of these neoplasms remains unclear. This study aimed to identify any potential association between the presence of hepatitis C virus (HCV) at the protein or gene level and epithelial salivary gland neoplasms. Methods: Formalin-fixed paraffin-embedded (FFPE) blocks of epithelial salivary gland neoplasms were retrieved from the archives of the Oral and Maxillofacial Pathology Department, Faculty of Dentistry, Cairo University within the 5-year period from 2016 to 2020. Immunohistochemistry was used to assess HCV core antigen, while reverse transcription polymerase chain reaction was employed for the evaluation of HCV RNA. Results: A total of 44 specimens were collected, 28 of which were benign neoplasms and 16 were malignant neoplasms. There was a statistically significant difference in HCV positivity between the two groups (P-value = 0.036). Benign tumors showed a statistically significant lower percentage of positive cases than malignant tumors. The localization of staining was also evaluated, revealing various patterns of HCV core antigen expression, including diffuse cytoplasmic, patchy cytoplasmic, nuclear, and a combination of nuclear and cytoplasmic expression. There was no statistically significant difference between the expression patterns in benign and malignant tumors (P-value = 0.616). Given that Pleomorphic Adenoma and Mucoepidermoid Carcinoma were the predominant tumor types in this study, four cases were selected for RNA detection. HCV RNA was detected in all cases using RT-PCR. Conclusions: HCV core antigen is frequently detected in SGNs and is suggested to be a potential risk factor for the development of these neoplasms. Further studies are required to discover other biomarkers, their roles, and the pathways associated with HCV in SGNs. [ABSTRACT FROM AUTHOR]

The hepatitis A virus (HAV) endemicity in the Philippines ranges from moderate to high. Despite this, health risks related to local seafood consumption are associated with red tide or mass fish kill. However, government agencies should consider the safety of local shellfish and culture sites to HAV. This article examines the current trends relevant to the presence of HAV along the local shellfish supply chain-including production levels, microbial concentration, consumer behavior, and food safety regulations. Despite the susceptibility of local shellfish to HAV, the study identified crucial data gaps: [1] reliance on bacterial indicators, [2] absence of monitoring records for HAV concentration in local shellfish products and culturing sites, and [3] limited studies regarding the effect of local cooking practices on HAV inactivation. The synthesis of this analysis will guide the national food safety risk managers in addressing the identified data gaps to facilitate a full-blown food risk analysis of HAV in Philippine shellfish. [ABSTRACT FROM AUTHOR]

This study investigated the potential associations between hepatitis virus antibody status and thyroid and inflammatory function. The C-reactive protein (CRP), thyroid-stimulating hormone (TSH), and free thyroxine (FT4) levels were measured in individuals with and without antibodies to the hepatitis A virus (HAV) and hepatitis B virus (HBV). Participants were stratified by age, sex, and HAV/HBV antibody status. Participants with and without antibodies to HAV and HBV had normal CRP, TSH, and FT4 levels. However, notable discrepancies were observed in FT4 levels among participants with HAV antibodies and in CRP and FT4 levels among those with both HAV and HBV antibodies, suggesting potential associations between viral immunity and thyroid function, especially in younger participants. Significant variations in thyroid hormone levels were noted when the sample was stratified by sex and HAV and HBV antibody status, indicating that the association between antibody status and thyroid hormone levels varied by sex. This study underscores the need for further research on the effect of viral immunity on inflammatory parameters and thyroid hormone levels. [ABSTRACT FROM AUTHOR]

The Hepatitis C Virus (HCV), with its diverse genotypes and subtypes, has significantly impacted the health of millions of people worldwide. Analyzing the risk factors is essential to understanding the spread of the disease and developing appropriate prevention strategies. This study aimed to identify risk factors associated with HCV subtype transmission and calculate the emergence time of subtype 1a in Mexico. A cross-sectional study was conducted from January 2014 to December 2018, involving 260 HCV-infected adults. HCV infection was confirmed via Enzyme-Linked Immunosorbent Assay, and viral load was measured by real-time PCR. Genotyping/subtyping tools were the Line Probe Assay and Sanger sequencing of the non-structural region 5B (NS5B). The most frequent HCV subtype was 1a (58.5%), followed by subtypes 1b (19.2%), 3a (13.1%), 2b (5.4%), 2a/2c (2.7%), 2a (0.8%), and 4a (0.4%). Intravenous drug use and tattoos were significant risk factors for subtypes 1a and 3a, while hemodialysis and blood transfusion were linked with subtype 1b. For the evolutionary analysis, 73 high-quality DNA sequences of the HCV subtype 1a NS5B region were used, employing a Bayesian coalescent analysis approach. This analysis suggested that subtype 1a was introduced to Mexico in 1976, followed by a diversification event in the mid-1980s. An exponential increase in cases was observed from 1998 to 2006, stabilizing by 2014. In conclusion, this study found that HCV subtypes follow distinct transmission routes, emphasizing the need for targeted prevention strategies. Additionally, the findings provide valuable insights into the origin of HCV subtype 1a. By analyzing the history, risk factors, and dynamics of the HCV epidemic, we have identified these measures: limiting the harm of intravenous drug trafficking, enhancing medical training and infrastructure, and ensuring universal access to antiviral treatments. The successful implementation of these strategies could lead to an HCV-free future in Mexico. [ABSTRACT FROM AUTHOR]

The innate immune system serves as the first line of defense against β-coronaviruses (β-CoVs), a family of viruses that includes SARS-CoV-2. Viral sensing via pattern recognition receptors triggers inflammation and cell death, which are essential components of the innate immune response that facilitate viral clearance. However, excessive activation of the innate immune system and inflammatory cell death can result in uncontrolled release of proinflammatory cytokines, resulting in cytokine storm and pathology. PANoptosis, innate immune, inflammatory cell death initiated by innate immune sensors and driven by caspases and RIPKs through PANoptosome complexes, has been implicated in the pathology of viral infections. Therefore, understanding the molecular mechanisms regulating PANoptosis in response to β-CoV infection is critical for identifying new therapeutic targets that can mitigate disease severity. In the current study, we analyzed findings from a cell death-based CRISPR screen with archetypal β-CoV mouse hepatitis virus (MHV) as the trigger to characterize host molecules required for inflammatory cell death. As a result, we identified SMARCA4, a chromatin regulator, as a putative host factor required for PANoptosis in response to MHV. Furthermore, we observed that gRNA-mediated deletion of Smarca4 inhibited MHV-induced PANoptotic cell death in macrophages. These findings have potential translational and clinical implications for the advancement of treatment strategies for β-CoVs and other infections. [ABSTRACT FROM AUTHOR]

In 2022, concurrent outbreaks of hepatitis A, invasive meningococcal disease (IMD), and mpox were identified in Florida, USA, primarily among men who have sex with men. The hepatitis A outbreak (153 cases) was associated with hepatitis A virus genotype IA. The IMD outbreak (44 cases) was associated with Neisseria meningitidis serogroup C, sequence type 11, clonal complex 11. The mpox outbreak in Florida (2,845 cases) was part of a global epidemic. The hepatitis A and IMD outbreaks were concentrated in Central Florida and peaked during March-June, whereas mpox cases were more heavily concentrated in South Florida and had peak incidence in August. HIV infection was more common (52%) among mpox cases than among hepatitis A (21%) or IMD (34%) cases. Where feasible, vaccination against hepatitis A, meningococcal disease, and mpox should be encouraged among at-risk groups and offered along with program services that target those groups. [ABSTRACT FROM AUTHOR]

Viral hepatitis is a systemic infectious diseases caused by various hepatitis viruses, primarily leading to liver damage. It is widely prevalent worldwide, with hepatitis viruses categorized into five types: hepatitis A, B, C, D, and E, based on their etiology. Currently, the detection of hepatitis viruses relies on methods such as enzyme-linked immunosorbent assay (ELISA), immunoelectron microscopy to observe and identify viral particles, and in situ hybridization to detect viral DNA in tissues. However, these methods have limitations, including low sensitivity, high error rates in results, and potential false negative reactions due to occult serum infection conditions. To address these challenges, we have designed an AuNPs-DNA walker method that uses gold nanoparticles (AuNPs) and complementary DNA strands for detecting viral DNA fragments through a colorimetric assay and fluorescence detection. The DNA walker, attached to gold nanoparticles, comprises a long walking strand with a probe sequence bound and stem-loop structural strands featuring a modified fluorescent molecule at the 3′ end, which contains the DNAzyme structural domain. Upon the addition of virus fragments, the target sequence binds to the probe chains. Subsequently, the long walking strand is released and continuously hybridizes with the stem-loop structural strand. The DNAzyme undergoes hydrolytical cleavage by Mg2+, breaking the stem-loop structural strand into linear single strands. As a result of these structural changes, the negative charge density in the solution decreases, weakening spatial repulsion and rapidly reducing the stability of the DNA walker. This leads to aggregation upon the addition of a high-salt solution, accompanied by a color change. Virus typing can be performed through fluorescence detection. The innovative method can detect DNA/RNA fragments with high specificity for the target sequence, reaching concentrations as low as 1 nM. Overall, our approach offers a more convenient and reliable method for the detection of hepatitis viruses. [ABSTRACT FROM AUTHOR]

Copyright of Viral Hepatitis Journal / Viral Hepatit Dergisi is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Viral Hepatitis Journal / Viral Hepatit Dergisi is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Hepatitis B Virus (HBV) is a hepatotropic virus that can establish a persistent and chronic infection in humans. Chronic hepatitis B (CHB) infection is associated with an increased risk of hepatic decompensation, cirrhosis, and hepatocellular carcinoma (HCC). Lactate level, as the end product of glycolysis, plays a substantial role in metabolism beyond energy production. Emerging studies indicate that lactate is linked to patient mortality rates, and HBV increases overall glucose consumption and lactate production in hepatocytes. Excessive lactate plays a role in regulating the tumor microenvironment (TME), immune cell function, autophagy, and epigenetic reprogramming. The purpose of this review is to gather and summarize the existing knowledge of the lactate's functions in the dysregulation of the immune system, which can play a crucial role in the development of HBV-related HCC. Therefore, it is reasonable to hypothesize that lactate with intriguing functions can be considered an immunomodulatory metabolite in immunotherapy. [ABSTRACT FROM AUTHOR]

Viral hepatitis, caused by its etiology, hepatitis virus, is a public health problem globally. Among all infections caused by hepatitis-associated viruses, hepatitis B virus (HBV) infection remains the most serious medical concern. HBV infection particularly affects people in East Asia and Africa, the Mediterranean region, and Eastern Europe, with a prevalence rate of > 2%. Currently, approximately 1 billion people worldwide are infected with HBV, and nearly 30% of them experience chronic infection. Chronic HBV infection can lead to chronic hepatitis B (CHB), liver cirrhosis, and hepatocellular carcinoma (HCC), resulting in the related death of approximately 1 million people annually. Although preventative vaccines and antiviral therapies are currently available, there is no cure for this infection. Clinical testing is not only the gateway for diagnosis of HBV infection, but also crucial for judging the timing of medication, evaluating the effect of antiviral therapy, and predicting the risk of relapse after drug withdrawal in the whole follow-up management of hepatitis B infected persons. With advances in detection technology, it is now possible to measure various viral components in the blood to assess the clinical status of HBV infection. Serum viral products of HBV infection, such as HBV DNA, HBV RNA, hepatitis B surface antigen, hepatitis B e-antigen, and hepatitis B core-related antigen, are non-invasive indicators that are critical for the rapid diagnosis and management of related diseases. Improving the sensitivity of monitoring of these products is essential, and the development of corresponding detection technologies is pivotal in achieving this goal. This review aims to offer valuable insights into CHB infection and references for its effective treatment. We provide a comprehensive and systematic overview of classical and novel methods for detecting HBV serum viral products and discusses their clinical applications, along with the latest research progress in this field. [ABSTRACT FROM AUTHOR]

Introduction: Hepatitis B virus (HBV) is one of the major public health problems globally and needs an urgent response. It is one of the most responsible causes of mortality among the five hepatitis viruses, and it affects almost every class of individuals. Different studies were conducted on the prevalence of HBV among pregnant women in East African countries, but none of them showed the pooled prevalence of HBV among the pregnant women. Thus, the main objective of this study was to determine the pooled prevalence and its determinants among pregnant women in East Africa. Methods: We searched studies using PubMed, Scopus, Embase, ScienceDirect, Google Scholar and grey literature that were published between January 01/2020 to January 30/2024. The studies were assessed using the Newcastle Ottawa Scale (NOS) quality assessment scale. The random-effect (DerSimonian) model was used to determine the pooled prevalence and associated factors of HBV among pregnant women. Heterogeneity were assessed by I2 statistic, sub-group analysis, and sensitivity analysis. Publication bias was assessed by Egger test, and the analysis was done using STATA version 17. Result: A total of 45 studies with 35639 pregnant women were included in this systematic review and meta-analysis. The overall pooled prevalence of HBV among pregnant women in East Africa was 6.0% (95% CI: 6.0%−7.0%, I2 = 89.7%). The highest prevalence of 8% ((95% CI: 6%, 10%), I2 = 91.08%) was seen in 2021, and the lowest prevalence 5% ((95% CI: 4%, 6%) I2 = 52.52%) was observed in 2022. A pooled meta-analysis showed that history of surgical procedure (OR = 2.14 (95% CI: 1.27, 3.61)), having multiple sexual partners (OR = 3.87 (95% CI: 2.52, 5.95), history of body tattooing (OR = 2.55 (95% CI: 1.62, 4.01)), history of tooth extraction (OR = 2.09 (95% CI: 1.29, 3.39)), abortion history(OR = 2.20(95% CI: 1.38, 3.50)), history of sharing sharp material (OR = 1.88 (95% CI: 1.07, 3.31)), blood transfusion (OR = 2.41 (95% CI: 1.62, 3.57)), family history of HBV (OR = 4.87 (95% CI: 2.95, 8.05)) and history needle injury (OR = 2.62 (95% CI: 1.20, 5.72)) were significant risk factors associated with HBV infection among pregnant women. Conclusions: The pooled prevalence of HBV infection among pregnant women in East Africa was an intermediate level and different across countries ranging from 1.5% to 22.2%. The result of this pooled prevalence was an indication of the need for screening, prevention, and control of HBV infection among pregnant women in the region. Therefore, early identification of risk factors, awareness creation on the mode of transmission HBV and implementation of preventive measures are essential in reducing the burden of HBV infection among pregnant women. [ABSTRACT FROM AUTHOR]

Background: Hepatitis A virus (HAV) is the predominant cause of acute viral hepatitis worldwide; however, data on HAV antibody prevalence (seroprevalence) among migrant populations are limited. This study aimed to investigate HAV seroprevalence among Qatar's migrant craft and manual workers (CMWs), constituting approximately 60% of the country's population. Methods: HAV antibody testing was conducted on stored serum specimens obtained from CMWs during a nationwide severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) population-based cross-sectional survey between July 26 and September 9, 2020. Associations with HAV infection were investigated through regression analyses. Results: Of the 2,607 specimens with HAV antibody test results, 2,393 were positive, and 214 were negative. The estimated HAV seroprevalence among CMWs was 92.0% (95% CI: 90.9–93.1%). HAV seroprevalence was generally high but exhibited some variation, ranging from 70.9% (95% CI: 62.4–78.2%) among Sri Lankans to 99.8% (95% CI: 98.2–99.9%) among Pakistanis. The multivariable regression analysis identified age, nationality, and educational attainment as statistically significant factors associated with HAV infection. Relative to CMWs aged ≤29 years, the adjusted relative risk (ARR) was 1.06 (95% CI: 1.03–1.10) in CMWs aged 30–39 years and reached 1.15 (95% CI: 1.10–1.19) in those aged ≥50 years. In comparison to Indians, the ARR was lower among Sri Lankans, assessed at 0.81 (95% CI: 0.72–0.91), but higher among Nepalese at 1.07 (95% CI: 1.04–1.11), Bangladeshis at 1.10 (95% CI: 1.07–1.13), Pakistanis at 1.12 (95% CI: 1.09–1.15), and Egyptians at 1.15 (95% CI: 1.08–1.23). No evidence for differences was found by geographic location or occupation. Conclusions: HAV seroprevalence among Qatar's CMW population is very high, with over nine out of every ten individuals having been exposed to this infection, likely during childhood. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to analyze the global profile of the nucleotide/nucleoside analogs (NAs) for chronic hepatitis virus therapy-related research. Background NAs, which closely resemble the structure of naturally occurring nucleotides/nucleosides, function by disrupting the elongation of the nascent DNA strand. These compounds are considered safe and well-tolerated, as they specifically target viral, but not human, polymerases involved in DNA replication. NAs are crucial in treating viral infections, including hepatitis, and are widely used due to their efficacy and safety. However, a study about trends in NAs for chronic hepatitis therapy-related research was never reported before. Methods The NAs for chronic hepatitis therapy-related research bibliometric analysis was performed on articles indexed in the Scopus database from 1986 to 2022. Results The total number of articles published worldwide is 2,341 documents, with an annual average of 65 documents. The United States generated the most articles (n = 486), followed byChina (n = 454), France (n = 191), and Italy (n = 179). Since 1992, the number of publications has increased dramatically worldwide. Globally, liver cell carcinoma, antiviral therapy, hepatitis B (e) antigen, and alanine aminotransferase are becoming hot research topics in the field. Conclusions This study provides a unique composite picture of NAs for chronic hepatitis therapy-related research worldwide and evaluates research productivity from 1986 to 2022. This finding suggests that the prospects for interventions in chronic hepatitis remain promising. [ABSTRACT FROM AUTHOR]

We evaluated factors associated with the presence of hepatitis A virus antibodies 23 years after initiating vaccination at ages 6–15 months. Among 67 participants, 86% (42/49) of those vaccinated at ages 12–15 months and 61% (11/18) of those vaccinated at 6 months remained seropositive at 23 years. Lack of maternal antibodies at enrollment and higher initial vaccine response were independently associated with higher antibody concentrations at 23 years. Further research is needed to assess the duration of hepatitis A vaccine protection and possible need for a booster dose. [ABSTRACT FROM AUTHOR]

This study assesses the prevalence of hepatitis D virus (HDV) in people living with HIV (PLWHIV) in Greece. Given the compounding effects of HDV and hepatitis B (HBV) on liver disease progression, as well as the emergence of new therapeutic options such as bulevirtide, understanding regional disparities and the epidemiological impact of such co-infections is vital. A cross-sectional analysis was conducted utilizing 696 serum samples from PLWHIV attending five major university hospitals. The methodology included HDV antibody detection by ELISA and HDV RNA confirmation. Of the 30 HBsAg-positive samples analyzed, the study population was primarily male (93%), with a median age of 54 years. Participants had been on antiretroviral therapy for a median of 10 years, and the median CD4 count was 738 (539–1006) copies/mL. Additional serological findings revealed a 7% prevalence of hepatitis C virus (HCV) IgG antibodies and a 55% prevalence of hepatitis A virus (HAV) IgG antibodies. Seroreactivity for syphilis (RPR/VDRL/TPHA positive) was identified in 33% of the participants. The results indicated a low HDV prevalence, with only one individual (3%) testing positive for anti-HDV IgG antibodies and none for HDV RNA. This indicates a lower prevalence of HDV among PLWHIV with chronic HBV in Greece compared to global data. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) infection leads to around 800,000 deaths yearly and is considered to be a major public health problem worldwide. However, HBV origins remain poorly understood. Here, we looked for bat HBV (BtHBV) in different bat species in Gabon to investigate the role of these animals as carriers of ancestral hepadnaviruses because these viruses are much more diverse in bats than in other host species. DNA was extracted from 859 bat livers belonging to 11 species collected in caves and villages in the southeast of Gabon and analyzed using PCRs targeting the surface gene. Positive samples were sequenced using the Sanger method. BtHBV DNA was detected in 64 (7.4%) individuals belonging to eight species mainly collected in caves. Thirty-six (36) sequences among the 37 obtained after sequencing were phylogenetically close to the RBHBV strain recently isolated in Gabonese bats, while the remaining sequence was close to a rodent HBV strain isolated in America. The generalized linear mixed model showed that the variable species best explained the occurrence of BtHBV infection in bats. The discovery of a BtHBV strain homologous to a rodent strain in bats raises the possibility that these animals may be carriers of ancestral hepadnaviruses. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the most frequent among primary liver tumors (90%) and one of the main causes of cancer-related death. It develops usually in a chronically inflamed environment, ranging from compensatory parenchymal regeneration to fibrosis and cirrhosis: carcinogenesis can potentially happen in each of these stages. Inflammation determined by chronic viral infection (hepatitis B, hepatitis C, and hepatitis delta viruses) represents an important risk factor for HCC etiology through both viral direct damage and immune-related mechanisms. The deregulation of the physiological liver immunological network determined by viral infection can lead to carcinogenesis. The recent introduction of immunotherapy as the gold-standard first-line treatment for HCC highlights the role of the immune system and inflammation as a double-edged weapon in both HCC carcinogenesis and treatment. In this review we highlight how the inflammation is the key for the hepatocarcinogenesis in viral, alcohol and metabolic liver diseases. [ABSTRACT FROM AUTHOR]

Hepatitis B is a serious threat to public health on a global scale. The Hepatitis B virus (HBV), which spreads both vertically and horizontally, is easily contracted by anyone. In 2020, the World Health Organization estimates that 257 million people worldwide have hepatitis B, and 900,000 people die from it each year. According to the World Health Organization (2021), there are approximately 39.4 million people in Southeast Asia living with chronic hepatitis B mortality, with 410,000 deaths caused by the disease. HBV can spread through injections, horizontal transmission, blood transfusions, and organ transplants. Cochrane, Science Direct, PubMed, Elsevier, Sage, Willey, DOAJ, and Google Scholar database sources were used to search for supported research on how to prevent hepatitis virus transmission in urban communities. 15 publications address the primary and secondary prevention of hepatitis B transmission in urban settings. Prevention keeps a person in good health and prevents them from progressing to a later, worse stage. Given that the hepatitis B virus can infect anyone, regardless of age, and that it affects people's health worldwide, as well as their families, communities, and families within them. In order to eradicate the hepatitis B virus, society must be aware of the importance of implementing preventive measures on a continuous and long-term basis through health advocacy activities, hepatitis B virus screening campaigns, health education, counseling, hepatitis B vaccination with community-based activities, and secondary prevention through combination therapy treatment in post-liver transplant patients. [ABSTRACT FROM AUTHOR]

There have been several Viral Hemorrhagic Fever (VHF) outbreaks in Nigeria which remains a public health concern. Despite the increasing number of suspected cases of VHF due to heightened surveillance activities and growing awareness, only a few cases are laboratory-confirmed to be VHF. Routinely, these samples are only tested for Lassa virus and Yellow fever virus with occasional testing for Dengue virus when indicated. The aetiology of the disease in these VHF suspected cases in Nigeria which are negative for Lassa, Yellow fever and Dengue viruses remains a puzzle. Since the clinical features exhibited by suspected VHF cases are like other endemic illnesses such as Hepatitis, there is a need to investigate the diversity and co-infections of hepatitis viruses as differentials and possible co-morbidity in suspected cases of VHFs in Nigeria. A total of three hundred and fifty (350) blood samples of 212 (60.6%) males and 138 (39.4%) females, aged <1–70 years with a mean age of 25 ±14.5, suspected of VHFs and tested negative for Lassa, Yellow fever and Dengue viruses were investigated for Hepatitis A, B, C and E viruses at the Centre for Human and Zoonotic Virology (CHAZVY), College of Medicine, University of Lagos (CMUL) using serologic and molecular techniques. The serologic analysis of these VHF suspected cases samples revealed that 126 (36%) were positive for at least one hepatitis virus. Individual prevalence for each of the hepatitis virus screened for showed that 37 (10.6%), 18 (5.1%) and 71 (20.3%) were positive for HBV, HCV and HEV respectively. All the samples were negative for HAV. A co-infection rate of 11.9% was also observed, with HCV/HEV co-infections being the most prevalent and the Northern region having the greatest burden of infection. The evidence of hepatitis virus infections in suspected cases of VHF was documented. Thus, their associations as co-morbidities and/or mortalities in this category of individuals require further investigations in endemic countries such as Nigeria. Therefore, the possible inclusion of screening for hepatitis viruses and other aetiologic agents that could mimic infections in suspected cases of VHFs in Nigeria should be thoroughly evaluated to guide informed policy on the diagnosis and management of these cases. [ABSTRACT FROM AUTHOR]

As adoptive cellular therapies become more commonplace in cancer care, there is a growing need to monitor site-specific localization of engineered cells—such as chimeric antigen receptor T (CAR-T) cells and T-cell receptor T (TCR-T) cells—in patients' tissues to understand treatment effectiveness as well as associated adverse events. Manufacturing CAR-T and TCR-T cells involves transduction with viral vectors commonly containing the WPRE gene sequence to enhance gene expression, providing a viable assay target unique to these engineered cells. Quantitative PCR (qPCR) is currently used clinically in fresh patient tissue samples and blood with target sequences specific to each immunotherapy product. Herein, we developed a WPRE-targeted qPCR assay that is broadly applicable for detection of engineered cell products in both fresh and archival formalin-fixed paraffin embedded (FFPE) tissues. Using both traditional PCR and SYBR Green PCR protocols, we demonstrate the use of this WPRE-targeted assay to successfully detect two CAR-T cell and two TCR-T cell products in FFPE tissue. Standard curve analysis reported a reproducible limit of detection at 100 WPRE copies per 20μL PCR reaction. This novel and inexpensive technique could provide better understanding of tissue abundance of engineered therapeutic T cells in both tumor and second-site toxicity tissues and provide quantitative assessment of immune effector cell trafficking in archival tissue. [ABSTRACT FROM AUTHOR]

Esophageal lesions are common findings in disorders of the digestive tract in patients living with HIV, the most typical symptoms being odynophagia and/or dysphagia. This article provides a narrative review of the spectrum of esophagitis in patients living with HIV, focusing on fungal, viral, bacterial and non-infectious etiologies, as well as co-infections with viral hepatitis viruses. The article provides a comprehensive approach to the strategy of diagnosis and the role of upper digestive endoscopy and histopathological examination in the evaluation of esophageal pathology in patients living with HIV. [ABSTRACT FROM AUTHOR]

The cellular prion protein (PrPC) is an extracellular cell membrane protein. Due to its diversified roles, a definite role of PrPC has been difficult to establish. During viral infection, PrPC has been reported to play a pleiotropic role. Here, we have attempted to envision the function of PrPC in the neurotropic m-CoV-MHV-RSA59-induced model of neuroinflammation in C57BL/6 mice. A significant upregulation of PrPC at protein and mRNA levels was evident in infected mouse brains during the acute phase of neuroinflammation. Furthermore, investigation of the effect of MHV-RSA59 infection on PrPC expression in specific neuronal, microglial, and astrocytoma cell lines, revealed a differential expression of prion protein during neuroinflammation. Additionally, siRNA-mediated downregulation of prnp transcripts reduced the expression of viral antigen and viral infectivity in these cell lines. Cumulatively, our results suggest that PrPC expression significantly increases during acute MHV-RSA59 infection and that PrPC also assists in viral infectivity and viral replication. [ABSTRACT FROM AUTHOR]

Hepatitis A virus (HAV), a member of the genus Hepatovirus (Picornaviridae HepV), remains a significant viral pathogen, frequently causing enterically transmitted hepatitis worldwide. In this study, we conducted an epidemiological survey of HepVs carried by small terrestrial mammals in the wild in Yunnan Province, China. Utilizing HepV-specific broad-spectrum RT-PCR, next-generation sequencing (NGS), and QNome nanopore sequencing (QNS) techniques, we identified and characterized two novel HepVs provisionally named EpMa-HAV and EpLe-HAV, discovered in the long-tailed mountain shrew (Episoriculus macrurus) and long-tailed brown-toothed shrew (Episoriculus leucops), respectively. Our sequence and phylogenetic analyses of EpMa-HAV and EpLe-HAV indicated that they belong to the species Hepatovirus I (HepV-I) clade II, also known as the Chinese shrew HepV clade. Notably, the codon usage bias pattern of novel shrew HepVs is consistent with that of previously identified Chinese shrew HepV. Furthermore, our structural analysis demonstrated that shrew HepVs differ from other mammalian HepVs in RNA secondary structure and exhibit variances in key protein sites. Overall, the discovery of two novel HepVs in shrews expands the host range of HepV and underscores the existence of genetically diverse animal homologs of human HAV within the genus HepV. [ABSTRACT FROM AUTHOR]

SUMOylation is an important protein post-translational modification (PTM) process, in which the small ubiquitin-like modifier (SUMO) protein covalently binds to the target protein and regulates stability, subcellular localization, and protein–protein interaction of the target protein. Protein SUMOylation exerts crucial regulatory function in the liver, and its abnormalities are associated with various liver-related disease processes. This review focuses on the biological functions of protein SUMOylation in liver-related diseases in recent years, summarizes the molecular mechanisms of SUMOylation in the replication of hepatitis viruses and the occurrence of hepatocellular carcinoma, and discusses the significance of SUMOylation in liver-related disorders, which is essential for understanding liver biological processes and formulating therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background and Objectives: Rotavirus and Hepatitis A virus are responsible for causing gastroenteritis and jaundice. The current vaccination approaches have proven insufficient, especially in low-income countries. In this study, we presented a novel dual-vaccine candidate that combines the rotavirus VP8 protein and the hepatitis A virus VP1. Materials and Methods: The VP8*-rotavirus+AAY+HAV-VP1 fusion protein was produced using an Escherichia coli expression system. The recombinant protein had a molecular weight of approximately 45.5 kDa and was purified through affinity chromatography. BALB/c mice were injected subcutaneously with the recombinant protein, VP1, VP8 and vaccines for rotavirus and hepatitis A virus, both with and without ALUM and M720 adjuvants. ELISA assays were used to measure total IgG, IgG1, IgG2, and short-term and long-term IL-5 and IFN-γ responses. Results: The fusion protein, when combined with adjuvants, elicited significantly higher total IgG, IgG1, and IgG2 responses compared to VP1 and VP8 alone, as well as the rotavirus and hepatitis A vaccines. Furthermore, it induced a higher short-term IL-5 and IFN-γ response while demonstrating a higher long-term IL-5 response compared to the rotavirus and hepatitis A vaccines. Conclusion: This study demonstrates that the VP8*-rotavirus+AAY+HAV-VP1 fusion protein is a promising dual vaccine candidate for immunization against hepatitis A and rotaviruses. [ABSTRACT FROM AUTHOR]

MHV-A59 is a beta-coronavirus that causes demyelinating encephalitis and hepatitis in mice. Recently, the mouse infection model of MHV-A59 has been used as an alternative animal infection model for SARS-CoV and SARS-CoV-2, aiding the development of new antiviral drugs. In this study, the MHV-A59 model was employed to investigate the potential of SARS-CoV-2 UTRs as new targets for antiviral drugs. Optimal targets within the MHV-A59 UTRs were identified using a shRNA and siRNA design tool, focusing on RNA secondary stem-loop (SL) structures in the UTRs. We then examined whether the designed RNAi constructs could inhibit MHV-A59 replication. In the 5′UTR, the stem-loop 1 (SL1) was identified as the most effective target, while in the 3′UTR, the minimal element for the initiation of negative-strand RNA synthesis (MIN) proved to be the most effective. Importantly, siRNAs targeting SL1 and MIN structures significantly reduced total RNA synthesis, negative-strand genomic RNA synthesis, subgenomic (sg) RNA synthesis, viral titer, and the plaque size of MHV-A59 compared to the control. Although not statistically significant, the combination of siSL1 and siMIN had a stronger effect on inhibiting MHV-A59 replication than either siRNA monotherapy. Interestingly, while the SL1 structure is present in both MHV and SARS-CoV-2, the MIN structure is unique to MHV. Thus, the SL1 of SARS-CoV-2 may represent a novel and promising target for RNAi-based antiviral drugs. [ABSTRACT FROM AUTHOR]

Metagenomic next-generation sequencing (mNGS) has enabled the high-throughput multiplexed identification of sequences from microbes of potential medical relevance. This approach has become indispensable for viral pathogen discovery and broad-based surveillance of emerging or re-emerging pathogens. From 2015 to 2019, plasma was collected from 9586 individuals in Cameroon and the Democratic Republic of the Congo enrolled in a combined hepatitis virus and retrovirus surveillance program. A subset (n = 726) of the patient specimens was analyzed by mNGS to identify viral co-infections. While co-infections from known blood-borne viruses were detected, divergent sequences from nine poorly characterized or previously uncharacterized viruses were also identified in two individuals. These were assigned to the following groups by genomic and phylogenetic analyses: densovirus, nodavirus, jingmenvirus, bastrovirus, dicistrovirus, picornavirus, and cyclovirus. Although of unclear pathogenicity, these viruses were found circulating at high enough concentrations in plasma for genomes to be assembled and were most closely related to those previously associated with bird or bat excrement. Phylogenetic analyses and in silico host predictions suggested that these are invertebrate viruses likely transmitted through feces containing consumed insects or through contaminated shellfish. This study highlights the power of metagenomics and in silico host prediction in characterizing novel viral infections in susceptible individuals, including those who are immunocompromised from hepatitis viruses and retroviruses, or potentially exposed to zoonotic viruses from animal reservoir species.

Background: Acute liver failure (ALF) is a serious condition that refers to the development of synthetic function impairment after severe acute liver injury in an individual without pre-existing liver disease. Understanding the epidemiology of ALF in children constitutes a cornerstone in its preventive and treatment plans. Nevertheless, there is a lack of information about its epidemiology in Egypt. Objective: The aim of this study was to assess the epidemiologic data of ALF in Egyptian children. Patients and methods: The medical records of children with ALF aged from 6 months to 18 years who were admitted from 2015 to 2020 were analyzed to identify the patient's epidemiologic, laboratory, and investigational data together with their outcome. Results: The study included 154 patients who fulfilled the definition of ALF were included. Their age ranged from 7 months to 17 years, with a median of 5.8 years. Hepatitis A virus (HAV) was the most commonly identifiable etiology (37.7%). Mortality was the outcome for 73 patients (47.4%). The prognostic factors associated with mortality were elevated international normalized ratio (INR), total bilirubin (TB), creatinine, and ammonia levels at presentation with cutoff values (2.97, 21.15, 0.385, and 212, respectively). Conclusion: Hepatitis A virus is the most commonly identified etiology of ALF in Egyptian children. The mortality rate is high, and most of the deaths occurred early in the first 5 days of admission. So, early preparation for liver transplantation is recommended. Higher values of INR, TB, and creatinine above the cutoff levels at presentation may be potential markers for predicting death in affected children. [ABSTRACT FROM AUTHOR]

The maintenance of viral protein homeostasis depends on the interaction between host cell proteins and viral proteins. As a molecular chaperone, heat shock protein 70 (HSP70) has been shown to play an important role in viral infection. Our results showed that HSP70 can affect translation, replication, assembly, and release during the life cycle of duck hepatitis A virus type 1 (DHAV-1). We demonstrated that HSP70 can regulate viral translation by interacting with the DHAV-1 internal ribosome entry site (IRES). In addition, HSP70 interacts with the viral capsid proteins VP1 and VP3 and promotes their stability by inhibiting proteasomal degradation, thereby facilitating the assembly of DHAV-1 virions. This study demonstrates the specific role of HSP70 in regulating DHAV-1 replication, which are helpful for understanding the pathogenesis of DHAV-1 infection and provide additional information about the role of HSP70 in infection by different kinds of picornaviruses, as well as the interaction between picornaviruses and host cells. [ABSTRACT FROM AUTHOR]

Introduction: Despite national goals to eliminate Hepatitis C (HCV) and the advancement of curative, well-tolerated direct-acting antiviral (DAAs) regimens, rates of HCV treatment have declined nationally since 2015. Current HCV guidelines encourage treatment of HCV by primary care providers (PCPs). Payors have reduced restrictions to access DAAs nationally and in California however it remains unclear if the removal of these restrictions has impacted the proportion of PCPs prescribing DAAs at a health system level. Our objective was to examine the proportion of DAAs prescribed by PCPs and specialists and to describe the population receiving treatment in a single health system from 2015 to 2022. Methods: We examined the proportion of DAAs prescribed by PCPs and specialists and the population receiving treatment through a retrospective analysis of claims data in the University of California, Los Angeles (UCLA) Health System from 2015 to 2022. We described number of prescriptions for HCV medication prescribed by PCPs and specialists by year, medication type, and physician specialty. We also described numbers of prescriptions by patient demographics and comorbidities. Results: A total of 1515 adult patients received a prescription for HCV medication through the UCLA Health System between 2015 and 2022. The proportion of patients receiving prescriptions for PCPs peaked at 19% in 2016, yet decreased to 5.7% in 2022, an average of 13% across all years. Median age of patients receiving treatment was 60 years old, and 56% of patients receiving HCV treatment had commercial insurance as their primary payer. Conclusions: HCV treatment declined from 2015 to 2022 among specialists and PCPs in our health system. Older patients comprised the majority of patients receiving treatment, suggesting a need for novel approaches to reach patients under 40, an age group with significant increases in HCV transmission. [ABSTRACT FROM AUTHOR]

Introduction: Infection with hepatitis A virus (HAV) is often asymptomatic in young children, but most adolescents and adults will have symptoms ranging from nausea and tiredness to acute liver failure and even death. The risk of severe disease is higher in older adults and people with pre-existing liver disease. Immunization is recommended in regions with low HAV endemicity levels, i.e., where people get infected later in life. In the Philippines, recent epidemiologic data on HAV infection are lacking. The objective of this study was to assess age-specific seroprevalence and evaluate risk factors associated with HAV seropositivity. Methods: People from two geographic areas (urban and rural) were recruited/enrolled and stratified by age group. HAV-specific immunoglobulin G (IgG) antibodies were measured with a chemiluminescent microparticle immunoassay. Sociodemographic parameters, hepatitis medical history, disease knowledge, hygiene measures and sanitation were assessed via a purpose-made questionnaire. Age at midpoint of population immunity (AMPI) was estimated using Kaplan-Meier curves. Logistic regression analyses were carried out to determine factors that were statistically significantly associated (p < 0.05) with HAV seropositivity. Results: Overall, 1242 participants were included in the analysis; 250/602 (41.5%) participants from urban regions and 283/640 (44.2%) participants from rural regions tested positive for HAV IgG antibodies. AMPI was 35 and 37 years for the rural and urban region, respectively. Higher education was associated with lower HAV seropositivity prevalence ratios, while not living in the same region for the last 5 years, regularly consuming street food and lack of handwashing after defecation were associated with a higher likelihood of HAV seropositivity. Conclusion: Results suggest that HAV endemicity is low in the Philippines. Factors associated with HAV seropositivity were traveling, consuming street food and lack of basic hygienic gestures. Immunization might be an option to protect vulnerable populations against severe hepatitis A disease. Plain Language Summary: Hepatitis A virus (HAV) is transmitted via the fecal-oral route through consumption of contaminated food or water or by close contact with an infected person. In children, HAV is usually of no concern, but in adults and people with existing liver disease, HAV infection can lead to severe symptoms and even death. In areas where most people get hepatitis during childhood (high endemicity), vaccination is not required, since people acquire life-long immunity after infection. In regions with low and intermediate HAV endemicity, people may remain at risk of infection later in life and vaccination could be considered to prevent severe HAV disease and its associated complications. In the Philippines, the current endemicity level is unknown. The goal of this study was to determine the endemicity level in the Philippines and to determine risk factors for HAV infection. We measured the proportion of people (by age group) who had previously been infected with HAV. Results showed that by age of 5 years < 20% of the study population was infected by HAV. By the age of 37 years in the urban population and 35 years in the rural population, 50% of people tested positive for HAV antibodies, indicating previous infection. This means that the Philippines has low HAV endemicity. Risk factors for HAV seropositivity were traveling, regularly eating street food and not washing hands after defecation. Vaccination against HAV might be of benefit in the Philippines, especially early in life to prevent most severe outcomes in adulthood. [ABSTRACT FROM AUTHOR]

Simple Summary: Duck hepatitis B virus was originally found in newly hatched Pekin ducks in the United States in 1980, which was followed by global spread and expansion to geese; thus, the virus may cause more financial damage to the poultry industry worldwide. In this study, an assay combining multienzyme isothermal rapid amplification (MIRA) and lateral flow dipstick (LFD) was developed for the efficient and rapid detection of DHBV. Followed by optimization testing of the reaction temperature and duration, the complete procedure for the newly developed MIRA assay for DHBV detection could be carried out by only using a water bath and only required 15 min. The newly developed MIRA assay was only confirmed to work with DHBV, had a 10 times higher sensitivity than the routine polymerase chain reaction (PCR) assay, and displayed better practicability for clinical samples. In line with these results, it was determined that the novel MIRA assay combined with LFD developed in this study would be a good alternative approach for DHBV detection in field clinics. Duck hepatitis B virus (DHBV) is widely prevalent in global ducks and has been identified in Chinese geese with a high prevalence; the available detection techniques are time-consuming and require sophisticated equipment. In this study, an assay combining multienzyme isothermal rapid amplification (MIRA) and lateral flow dipstick (LFD) was developed for the efficient and rapid detection of DHBV. The primary reaction condition of the MIRA assay for DHBV detection was 10 min at 38 °C without a temperature cycler. Combined with the LFD assay, the complete procedure of the newly developed MIRA assay for DHBV detection required only 15 min, which is about one-fourth of the reaction time for routine polymerase chain reaction assay. And electrophoresis and gel imaging equipment were not required for detection and to read the results. Furthermore, the detection limit of MIRA was 45.6 copies per reaction, which is approximately 10 times lower than that of a routine polymerase chain reaction assay. The primer set and probe had much simpler designs than loop-mediated isothermal amplification, and they were only specific to DHBV, with no cross-reactivity with duck hepatitis A virus subtype 1 and duck hepatitis A virus subtype 3, goose parvovirus, duck enteritis virus, duck circovirus, or Riemerella anatipestifer. In this study, we offer a simple, fast, and accurate assay method to identify DHBV in clinical serum samples of ducks and geese, which would be suitable for widespread application in field clinics. [ABSTRACT FROM AUTHOR]

Background: Cytokines/chemokines play essential roles in the occurrence and progression of hepatitis B virus (HBV) infection. This study aimed to observe the expression patterns of 10 related cytokines/chemokines in the serum of healthy individuals, self-limited patients and HBV-infected patients at different stages of disease (chronic hepatitis B (CHB), liver cirrhosis (LC), hepatocellular dysplastic nodules (DNs) and hepatocellular carcinoma (HCC)) and to analyze the relationships of these cytokines/chemokines with disease progression. Methods: The levels of six cytokines (FGF-2, IFN-α2, IL-4, IL-6, IL-10 and VEGF-A) and four chemokines (GRO-α, IL-8, IP-10 and MCP-1) were quantified using Luminex multiplex technology. Results: There were no significant differences in the expression of the 10 cytokines/chemokines between healthy individuals and self-limited patients. The levels of IL-4, IL-6, and IL-8 increased significantly in the CHB and LC groups. IL-10 was highly expressed in the HCC group. The level of IP-10 was significantly greater in all liver disease groups (CHB, LC, DN and HCC) than in the HI and SL-HBV groups, while the level of GRO was significantly lower in all liver disease groups than in the HI and SL-HBV groups. The levels of the 10 cytokines/chemokines were not significantly different between the preoperative group and the two-day postoperative group. Significant increases in the levels of IL-4, VEGF-A and IL-8 and significant decreases in those of IL-10 and GRO-α were observed 3 months after surgery. Correlation analysis revealed that most of the cytokines/chemokines with significant correlation differences were positively correlated before and after HCC surgery. Conclusion: Our results highlight the fluctuating status of specific cytokines in HBV infection-related disease progression. It is speculated that these cytokines may be used as serum markers to monitor dynamic changes during the progression of HBV-related liver disease and to predict patient prognosis. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) causes liver diseases (chronic hepatitis, cirrhosis, and hepatocellular carcinoma) and is a leading health problem worldwide. Sequencing of the whole HBV genome provides insight into the virus genotype, subgenotype, serotype, genetic variation, and viral drug resistance. To date, no study has been conducted on the whole genome sequence of HBV obtained from Iraqi patients. Therefore, this is the first study to sequence clinical samples from these patients. Viral genomic DNA was isolated and amplified using five primer sets to amplify five overlapping regions covering the entire HBV genome. The amplicons were sequenced, aligned to a reference sequence, annotated, and submitted to the National Center for Biotechnology Information GenBank database. Sequence analysis showed that the genome size of the tested viral samples was 3,182 bp and belonged to genotype D, subgenotype D1, and serotype ayw2. Missense mutations were found in the four regions (X, PreS1-S, PreC-C, and P) of the tested samples, leading to amino acid substitutions, which were 8.4%, 5.1%, 4.7%, and 4.6%, respectively. These mutations may cause severe liver diseases. [ABSTRACT FROM AUTHOR]