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Pathogens
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Viral Hepatitis in Europe: The Unresolved Issues
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Viral Hepatitis in Europe: The Unresolved Issues

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Viral Pathogens".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 11320

Special Issue Editors

Prof. Dr. Ivana Lazarevic

E-Mail Website
Guest Editor
Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Dr Subotica 1, 11000 Belgrade, Serbia
Interests: virology; hepatitis viruses; HBV; viral genetic variability; immune escape; drug resistance; diagnostic methods
Dr. Valentina Svicher

E-Mail Website
Guest Editor
Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy
Interests: SARS-CoV-2; drug resistance; immune escape; HBV chronic infection; HBV reactivation; hepatocellular carcinoma; HIV; HDV
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Hepatitis viruses are estimated to infect between 1.6 and 3.1% of the population in Europe, with their prevalence differing markedly between western and eastern regions. The overall hepatitis morbidity and mortality rates have declined in recent decades due to universal anti-HBV vaccination programs, better surveillance systems, and new efficient therapies. However, there are still significant challenges in the management of viral hepatitis as a result of the high frequency of asymptomatic and often undiagnosed cases, high disease burden in older generations, and the rise in its incidence associated with foreign immigration.

Some of the issues in the management of HCV infection still include difficult-to-treat chronic patients, the development of vaccines and sensitive surveillance diagnostic methods for treated patients, and the availability of screening in populations at a high risk of infection and in resource-limited areas. In HBV infection, the inability to reach sterilizing cures via current therapies has developed the need for new non-invasive biomarkers capable of reflecting the intrahepatic activity of the virus. Extrahepatic manifestations and chronic infection in immunocompromised individuals have identified HEV infection as an emerging health problem, even in regions with sporadic transmission.

This Special Issue invites original research and review articles covering advancements in the diagnosis, prevention, and therapy of viral hepatitis in European countries.

Prof. Dr. Ivana Lazarevic
Dr. Valentina Svicher
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • viral hepatitis
  • Europe
  • HBV
  • HCV
  • HEV
  • clinical management
  • diagnostic methods
  • new biomarkers
  • antiviral therapy
  • vaccines

Published Papers (7 papers)

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Research

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10 pages, 837 KiB  
Communication
Screening for Hepatitis C Virus Reinfection Using a Behaviour-Based Risk Score among Men Who Have Sex with Men with HIV: Results from a Case–Control Diagnostic Validation Study
by Kris Hage, Marita van de Kerkhof, Anders Boyd, Joanne M. Carson, Astrid M. Newsum, Amy Matser, Marc van der Valk, Kees Brinkman, Joop E. Arends, Fanny N. Lauw, Bart J. A. Rijnders, Arne van Eeden, Marianne Martinello, Gail V. Matthews, Janke Schinkel and Maria Prins
Pathogens 2023, 12(10), 1248; https://doi.org/10.3390/pathogens12101248 - 16 Oct 2023
Viewed by 1038
Abstract
We assessed the predictive capacity of the HCV-MOSAIC risk score, originally developed for primary early HCV infection, as a screening tool for HCV reinfection in 103 men who have sex with men (MSM) with HIV using data from the MOSAIC cohort, including MSM [...] Read more.
We assessed the predictive capacity of the HCV-MOSAIC risk score, originally developed for primary early HCV infection, as a screening tool for HCV reinfection in 103 men who have sex with men (MSM) with HIV using data from the MOSAIC cohort, including MSM with HIV/HCV-coinfection who became reinfected (cases, n = 27) or not (controls, n = 76) during follow-up. The overall predictive capacity of the score was assessed using the area under the receiver operating characteristic (AUROC) curve. The effects of covariates on the receiver operating characteristic (ROC) curve were assessed using parametric ROC regression. The score cut-off validated for primary early infection (≥2.0) was used, from which the sensitivity and specificity were calculated. The AUROC was 0.74 (95% confidence interval (CI) = 0.63–0.84). Group sex significantly increased the predictive capacity. Using the validated cut-off, sensitivity was 70.4% (95%CI = 49.8–86.2%) and specificity was 59.2% (95%CI: 47.3–70.4%). External validation from a cohort of 25 cases and 111 controls, all MSM with HIV, resulted in a sensitivity of 44.0% (95%CI = 24.4–65.1) and specificity of 71.2% (95%CI = 61.8–79.4). The HCV-MOSAIC risk score may be useful for identifying individuals at risk of HCV reinfection. In sexual health or HIV-care settings, this score could help guide HCV-RNA testing in MSM with a prior HCV infection. Full article
(This article belongs to the Special Issue Viral Hepatitis in Europe: The Unresolved Issues)
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8 pages, 451 KiB  
Communication
Natural History and Hepatitis B Virus Surface Antigen (HBsAg) Spontaneous Seroclearance in Hepatitis B Virus e-Antigen (HBeAg)-Negative Patients with Inactive Chronic Infection: A Multicenter Regional Study from South Italy
by Michele Barone, Andrea Iannone, Martino Mezzapesa, Michele Milella, Francesco Di Gennaro, Grazia Niro, Rosa Cotugno, Raffaele Cozzolongo, Giuseppe Mennea, Maria Rendina and Alfredo Di Leo
Pathogens 2023, 12(10), 1198; https://doi.org/10.3390/pathogens12101198 - 26 Sep 2023
Viewed by 830
Abstract
Spontaneous HBsAg seroclearance has been mainly studied in populations from Asia, Australia, the Pacific Islands, and Polynesia. For the first time, we evaluated the spontaneous HBsAg seroclearance and its possible associated factors and the risk of disease progression in HBeAg-negative patients with inactive [...] Read more.
Spontaneous HBsAg seroclearance has been mainly studied in populations from Asia, Australia, the Pacific Islands, and Polynesia. For the first time, we evaluated the spontaneous HBsAg seroclearance and its possible associated factors and the risk of disease progression in HBeAg-negative patients with inactive infection all coming from the same region in South Italy. In this multicenter retrospective study, 146 patients were selected after 18 months of observation and followed for a median of 82 months (IQR 60–107). For our analyses, they were divided into three groups based on their HBsAg levels: <100 IU/mL, 100–1000 IU/mL, and >1000 IU/mL. Crude and adjusted hazard ratios (HRs) for HBsAg seroclearance were determined. During the follow-up period, three patients (2.0%) showed a disease progression with an increased liver stiffness, whereas 17 (11.6%) cleared the HBsAg. Patients with HBsAg levels <100 IU/mL had the highest probability of HBsAg seroclearance compared to the other two groups (p = 0.009). In the multivariate analysis, the HBsAg level <100 IU/mL was the only parameter independently associated with HBsAg seroclearance (adjusted HR = 3.53; CI 1.29–9.69; p = 0.01). In patients with chronic HBV inactive infection, HBsAg levels <100 IU/mL predicted the highest probability of HBsAg seroclearance. Full article
(This article belongs to the Special Issue Viral Hepatitis in Europe: The Unresolved Issues)
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11 pages, 1305 KiB  
Article
Significance of Circulating Cell-Free DNA Biomarkers in HBeAg-Negative Chronic Hepatitis B Virus Infection and Their Changes after Treatment Initiation
by Nikolaos D. Karakousis, Lampros Chrysavgis, Alkistis Papatheodoridi, Aigli-Ioanna Legaki, Panagiotis Lembessis, Evangelos Cholongitas, Antonios Chatzigeorgiou and George Papatheodoridis
Pathogens 2023, 12(3), 394; https://doi.org/10.3390/pathogens12030394 - 1 Mar 2023
Viewed by 1339
Abstract
Background: Chronic hepatitis B virus (HBV) infection is a common chronic liver disease that is closely associated with increased morbidity and mortality. Circulating cell-free DNA (cf-DNA) and global DNA methylation, expressed as circulating levels of 5-methyl-2′-deoxycytidine, are increasingly used to monitor chronic inflammatory [...] Read more.
Background: Chronic hepatitis B virus (HBV) infection is a common chronic liver disease that is closely associated with increased morbidity and mortality. Circulating cell-free DNA (cf-DNA) and global DNA methylation, expressed as circulating levels of 5-methyl-2′-deoxycytidine, are increasingly used to monitor chronic inflammatory diseases of several etiologies. This study attempts to investigate the serum levels of circulating cf-DNA and 5-methyl-2′-deoxycytidine in HBeAg-negative patients with chronic infection (carriers) and chronic hepatitis B (CHB), as well as their changes after treatment initiation in CHB. Methods: Serum samples from a total of 61 HBeAg-negative patients (30 carriers and 31 CHB patients) were included in order to quantify the levels of circulating cf-DNA and 5-methyl-2′-deoxycytidine. In addition, serum samples from 17 CHB patients in complete virological and biochemical remission after initiation of treatment with a nucleos(t)ide analogue were included. Results: Circulating cf-DNA concentration was significantly increased after the initiation of treatment (15 vs. 10 ng/mL, p = 0.022). There was a trend in higher mean levels of circulating 5-methyl-2′-deoxycytidine in carriers compared to CHB patients (211.02 vs. 175.66 ng/mL, p = 0.089), as well as a trend in increasing 5-methyl-2′-deoxycytidine levels after treatment initiation in CHB patients compared to pre-treatment levels (215 vs. 173 ng/mL, p = 0.079). Conclusions: Both circulating levels of cf-DNA and 5-methyl-2′-deoxycytidine might be useful biomarkers in order to monitor liver disease activity and response to antiviral treatment in HBeAg-negative chronic HBV patients, but further studies are essential in order to validate these intriguing findings. Full article
(This article belongs to the Special Issue Viral Hepatitis in Europe: The Unresolved Issues)
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Review

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16 pages, 1695 KiB  
Review
Metabolic Dysfunction-Associated Fatty Liver Disease and Chronic Viral Hepatitis: The Interlink
by Cornelius J. Fernandez, Mohammed Alkhalifah, Hafsa Afsar and Joseph M. Pappachan
Pathogens 2024, 13(1), 68; https://doi.org/10.3390/pathogens13010068 - 10 Jan 2024
Cited by 1 | Viewed by 1623
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) has now affected nearly one-third of the global population and has become the number one cause of chronic liver disease in the world because of the obesity pandemic. Chronic hepatitis resulting from hepatitis B virus (HBV) and [...] Read more.
Metabolic dysfunction-associated fatty liver disease (MAFLD) has now affected nearly one-third of the global population and has become the number one cause of chronic liver disease in the world because of the obesity pandemic. Chronic hepatitis resulting from hepatitis B virus (HBV) and hepatitis C virus (HCV) remain significant challenges to liver health even in the 21st century. The co-existence of MAFLD and chronic viral hepatitis can markedly alter the disease course of individual diseases and can complicate the management of each of these disorders. A thorough understanding of the pathobiological interactions between MAFLD and these two chronic viral infections is crucial for appropriately managing these patients. In this comprehensive clinical review, we discuss the various mechanisms of chronic viral hepatitis-mediated metabolic dysfunction and the impact of MAFLD on the progression of liver disease. Full article
(This article belongs to the Special Issue Viral Hepatitis in Europe: The Unresolved Issues)
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22 pages, 1116 KiB  
Review
Hepatitis B Surface Antigen Isoforms: Their Clinical Implications, Utilisation in Diagnosis, Prevention and New Antiviral Strategies
by Ivana Lazarevic, Ana Banko, Danijela Miljanovic and Maja Cupic
Pathogens 2024, 13(1), 46; https://doi.org/10.3390/pathogens13010046 - 3 Jan 2024
Viewed by 2447
Abstract
The hepatitis B surface antigen (HBsAg) is a multifunctional glycoprotein composed of large (LHB), middle (MHB), and small (SHB) subunits. HBsAg isoforms have numerous biological functions during HBV infection—from initial and specific viral attachment to the hepatocytes to initiating chronic infection with their [...] Read more.
The hepatitis B surface antigen (HBsAg) is a multifunctional glycoprotein composed of large (LHB), middle (MHB), and small (SHB) subunits. HBsAg isoforms have numerous biological functions during HBV infection—from initial and specific viral attachment to the hepatocytes to initiating chronic infection with their immunomodulatory properties. The genetic variability of HBsAg isoforms may play a role in several HBV-related liver phases and clinical manifestations, from occult hepatitis and viral reactivation upon immunosuppression to fulminant hepatitis and hepatocellular carcinoma (HCC). Their immunogenic properties make them a major target for developing HBV vaccines, and in recent years they have been recognised as valuable targets for new therapeutic approaches. Initial research has already shown promising results in utilising HBsAg isoforms instead of quantitative HBsAg for correctly evaluating chronic infection phases and predicting functional cures. The ratio between surface components was shown to indicate specific outcomes of HBV and HDV infections. Thus, besides traditional HBsAg detection and quantitation, HBsAg isoform quantitation can become a useful non-invasive biomarker for assessing chronically infected patients. This review summarises the current knowledge of HBsAg isoforms, their potential usefulness and aspects deserving further research. Full article
(This article belongs to the Special Issue Viral Hepatitis in Europe: The Unresolved Issues)
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17 pages, 2836 KiB  
Review
Future Prospects, Approaches, and the Government’s Role in the Development of a Hepatitis C Virus Vaccine
by Ashraf A. Tabll, Sayed S. Sohrab, Ahmed A. Ali, Ana Petrovic, Sabina Steiner Srdarevic, Stjepan Siber, Marija Glasnovic, Robert Smolic and Martina Smolic
Pathogens 2024, 13(1), 38; https://doi.org/10.3390/pathogens13010038 - 31 Dec 2023
Viewed by 1611
Abstract
Developing a safe and effective vaccine against the hepatitis C virus (HCV) remains a top priority for global health. Despite recent advances in antiviral therapies, the high cost and limited accessibility of these treatments impede their widespread application, particularly in resource-limited settings. Therefore, [...] Read more.
Developing a safe and effective vaccine against the hepatitis C virus (HCV) remains a top priority for global health. Despite recent advances in antiviral therapies, the high cost and limited accessibility of these treatments impede their widespread application, particularly in resource-limited settings. Therefore, the development of the HCV vaccine remains a necessity. This review article analyzes the current technologies, future prospects, strategies, HCV genomic targets, and the governmental role in HCV vaccine development. We discuss the current epidemiological landscape of HCV infection and the potential of HCV structural and non-structural protein antigens as vaccine targets. In addition, the involvement of government agencies and policymakers in supporting and facilitating the development of HCV vaccines is emphasized. We explore how vaccine development regulatory channels and frameworks affect research goals, funding, and public health policy. The significance of international and public-private partnerships in accelerating the development of an HCV vaccine is examined. Finally, the future directions for developing an HCV vaccine are discussed. In conclusion, the review highlights the urgent need for a preventive vaccine to fight the global HCV disease and the significance of collaborative efforts between scientists, politicians, and public health organizations to reach this important public health goal. Full article
(This article belongs to the Special Issue Viral Hepatitis in Europe: The Unresolved Issues)
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Other

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8 pages, 267 KiB  
Perspective
Is It Time for Treatment as Prevention of Chronic Hepatitis B?
by Jose A. Perez-Molina, Marta Rosas Cancio-Suárez and Santiago Moreno
Pathogens 2023, 12(9), 1137; https://doi.org/10.3390/pathogens12091137 - 6 Sep 2023
Viewed by 1169
Abstract
Hepatitis B is a major global health problem with high morbidity and mortality. Approximately 296 million people are living with chronic HBV, and 1.5 million new infections are detected each year, even though a highly effective vaccine has been available for decades and [...] Read more.
Hepatitis B is a major global health problem with high morbidity and mortality. Approximately 296 million people are living with chronic HBV, and 1.5 million new infections are detected each year, even though a highly effective vaccine has been available for decades and viral replication and transmission can be contained with the use of drugs. Nucleoside therapy, while not curative in most cases, can control viral replication, improve prognosis, and prevent mother-to-child transmission safely. Current treatment guidelines do not include a significant number of chronically infected patients or pregnant women and are often complex to implement. Since these populations continue to have a detectable HVB viral load, they could perpetuate transmission. Expanding and facilitating treatment indications, including treatment as a public health intervention, could help control the spread of the HBV pandemic, thus bringing us closer to the goal of the United Nations General Assembly for the year 2030. Full article
(This article belongs to the Special Issue Viral Hepatitis in Europe: The Unresolved Issues)
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